PharTech Book Tutor Small

C mpr
Com
reh
hens
nsive
ve
229
[ 9 25554]
PART I:
Preformulation
Solubilization
Partition
Buffer and Isotonicity
Micrometrics
Rheology
Incompatibility
Pharmaceutical Necessities
Polymorphism & Eutectics
Adsorption & Interfacial
Phenomena
Part I
Comprehensive Examination
Page 1 of 68
Solubilization
1.
2.
3.
4.
5.
By>> Sim 058 & Bow 083
: 2

: 2
ExM,N,%w/w,%w/v,%v/v

(excess
solute)
symbol
:
/

(Meltingpoint)
Rx 29
: ( )

meta>orto>para

Rx 29
Rx 29
:
LIKE DISSOLVE LIKE
polarity ( dielectric constant, )

polarity (co-solvent)
: ethanol, glycerin,
propylene glycol, polyethylene glycol, sorbitol etc.
mix = (wt. fraction of A) A + (wt. fraction of B) B

: 30% ethanol
( =25) 70% water ( =80)
mix = (30/100) 25 + (70/100) 80

= 63.5
Rx 29
06/09/11
Rx 29
Created by Pharmacy Student. Department of Pharmaceutical Technology PSU Rx'29
Part I

:Additive
Page 2 of 68
pHp pH pH pHp

pHp pH pH pHp
free base
Rx 29
Rx 29
: pH phenobarbital
phenobarbital sodium 1%w/v
25oC phenobarbital (SO) = 0.005 M,
pKa = 7.41 MW= 254
S = 10/254 = 0.39 M
Additive
Saltingout:

ammoniumsulfate
Saltingin:
Surfactant: micelle
= 8.24
Rx 29
Rx 29
surfactants
O- Na+
HO-S=O
H2C
CH
H2C 2
CH
H3C 2
CH
H2C 2
CH
H3C 2
CH
H2C 2
CH3

1.IonicSurfactants
AnionicSurfactants
CationicSurfactants
ZwitterionicSurfactants
2.NonionicSurfactants
Rx 2911
06/09/11
Sodiumlauryl Sulfate
AnionicSurfactants
Soap
Alkyl sulfate
Alkyl Sulfonate
R-COOR-OSO3R-SO3-
Rx 2912
Part I
CH3
Br+
H3C-N-CH
3
H2C
CH
H2C 2
CH
H3C 2
CH
H2C 2
CH
H3C 2
CH
H2C 2
CH3
CationicSurfactants
Alkyl ammonium
R-NH3+
Alkyl trimethylammonium R-N(CH3)+
R-NC5H5+
Alkyl pyridinium
Page 3 of 68
ZwitterionicSurfactant
R-N+CH2-COOR-N+C(CH3)2CH2COO-
N-Alkyl glycine
N-Alkyl betains
Phosphatidyl choline (Lecithin)

R-O-CH-CH-O-PO3--CH2-CH2-N(CH3)3+
R-O-CH2
Lauramide
Rx 2913
Rx 2914
NonionicSurfactants
HLB
(HydrophilicLipophilic Balance)
Polar: -OH, -O-,

(-O-CH2-CH2)n Polyoxyethylene
Spans
(Sorbitan esters)
Tweens
(Polyoxyethylene derivatives Spans)
HLB
HLB
Rx 2915
18
15
12
9
6
3
0
Solubilizing agents
Detergents
O/W emulsifying agents
06/09/11
FICKS FIRST LAW OF DIFFUSION

-L-
W/O emulsifying agents

Most antifoaming agents
HLBScale
Rx 29
C1 C2
= DA (C1 - C2)
L
D = Diffusion coefficient of solute
Rx 29
A = surface area of solute

C1 =
C2 = stagnant layer
Rx 29
L = stagnant layer
Part I
= DA (C1 - C2)
L
C2 <<< C1
C1 = saturated solubility (S)
Page 4 of 68
Completemiscibility:
Partialmiscibility:
Immiscibility:
emulsion
= DA (S)
L

Rx 29
1. 2

2. 3
Phase Rule F = C - P +2
F: # degree of freedom in system # independent variables (e.g. T, P,
conc.) for explaining the system
C: # of components

P: # phases in system
Rx 29
P2
Liquid
P1
4.58
(mmHg)
H2O
( T, P)
H2O, alcohol C = 2 Fmax = 3
( T, P, conc)
Condensed system
(T, conc.)
(at constant P)
Fmax = 2
Rx 29
At constant P
T1
Fmax = 2
One phase
Fmax = 3
(T, P, conc.)
O Gas
0.098
C =1
Water-phenol
C
T (Co)
Rx 29
06/09/11
F = C - P +2
H2 O
D
Solid
Rx 29
F=2
P=2
Two phases
BINODAL CURVE
% w/w of phenol in water
Rx 29
Part I
Page 5 of 68
One phase
50 -
50 -
Two phases
0
One phase
h
d
Two phases
100
tie line
conjugate solution
11%
63%
100
Rx 29
Rx 29
critical solution temperature

h
66.8
50 -
100
Rx 29
Upper CST
+ Naphthalene
% w/w of Nicotine in water

Lower CST
06/09/11
% w/w of TEA in water

Lower consolute temperature
Rx 29
+ Succinic acid
Rx 29
Salting-out
% w/w of Phenol in water
blinding
Rx 29
Part I
Page 6 of 68
100% B
Fmax = 4 ( T, P, conc1, conc2)

T, P
F=2
P=2
Rx 29
100% A
100% C
Rx 29
100% B
100% B
40% A
40% B
100% A
30% A
100% C
Rx 29
3
2
100% A
one phase
l
e
A: water a
06/09/11
Rx 29
B : alcohol
T, P
-benzene alcohol
3 alcohol
benzene benzene
Rx 29
100% C
40% B
m
g
d
i
f
two phases
%B
C: benzene
Rx 29
Part I
B : alcohol
T, P
one phase
l m
Page 7 of 68
Solvent effect
cosolvent
A/
C/
B/
T3 > T2 > T1
T3
T2
A: water a
(x% A, y%B, z% C) e
c C: benzene
f (a%A, b%B, c% C)
T1
C
Rx 29
Exercise
20
50% tieline

bimodal 8.4 72.2%w/w

500

Rx 29
Rx 29
100 = 50%
500 = 250
X
500-X
20 100 8.4
x 8.4 x/100
20 100 72.2
500-x 72.2(500-x)/100
(72.2(500-x)/100)+(8.4x/100) =250
X
=174

174
500-174 =326

100 = 8.4
174 8.4x174/100= 15
250-15=235
Rx 29
Rx 29
06/09/11
Part I
Page 8 of 68
Solubilization
1.
/

(Melting point)
cohesive force

meta>ortho>para

polarity dielectric constant :

polarity (co-solvent)
: ethanol, glycerin, propylene glycol,
polyethylene glycol, sorbitol etc.
06/09/11
Part I
Page 9 of 68
mix = (wt. fraction of A) A + (wt. fraction of B) B
: 30% ethanol ( =25) 70%

water ( =80)
mix = (30/100) 25 + (70/100) 80
= 63.5

1.1 Exothermic W (+) = W22 + W11 - W21
1.2 Endothermic W (-) = W22 + W11 - W21
W22 =
W11 =
W12 =
-
WEAK ACIDIC DRUG
HA + H2O
H3O+ + A-
Ka = [H3O+][A-]
[HA]
(S) (A-) (HA)
S = [HA] + [A-]
[HA] = SO
S = SO + [A-]
06/09/11
Part I
pH p pK a log
Page 10 of 68
( S So )
So
pHp pH pH pHp
pH p pKW pK b log
So
S So
pHp pH pH pHp
free base
( Additive )
Salting-out :
ammonium sulfate
Salting-in:
Surfactant : micelle
surfactants
1. Ionic Surfactants
- Anionic Surfactants
: Sodium lauryl Sulfate
- Cationic Surfactants : Alkyl ammonium , Alkyl trimethylammonium

- Zwitterionic Surfactants : Phosphatidyl choline (Lecithin), N-Alkyl betains
2. Nonionic Surfactants Tween, span
(Hydrophilic-Lipophilic Balance):HLB

06/09/11
HLB
HLB
Part I
Page 11 of 68

NaCl AgCl

sodium
06/09/11
Part I
Page 12 of 68
FICKS FIRST LAW OF DIFFUSION
-L-
C1 C2
= DA (C1 - C2)
L
D = Diffusion coefficient of solute

A = surface area of solute
C1 =
C2 = stagnant layer
L = stagnant layer
C2 <<< C1 C1 = saturated solubility (S)
06/09/11
Part I
Page 13 of 68
1. Complete miscibility : -alcohol, benzene-CCl4

2. Partial miscibility: 2
3. Immiscibility:
emulsion
(Phase Equilbria and The Phase Rule)

J.Willard Gibbs
( )
(component)
F=CP+2
F = (degree of freedom)
C =
P =
06/09/11
Part I
P2
P1
4.58
Page 14 of 68
Liquid
H2O
D
Soli
O Ga
C
0.098
T1
T (Co)

,
, D 2 (F = C B + 2 = 1
1+ 2 = 2) (bivariant, F = 2) 2 P2 T2
2 , ,

AO, BO, CO E
OA 1(F = C B + 2 = 1 2 -+ 2 = 1)
(univariant,F = 1) P1 T1 E
3 O
0 (F = c-p+2 = 1-3-+2 = 0) (invariant, F=0)
06/09/11
Part I
Page 15 of 68
+
F
= C P +2
= 1-2+2
=1

2
g b h c:f bimodal curve 2

50 100%
b 2
11 % 50 2
c 63%
bc 2
tie line 2 (base line)
tie line def 2 11% 89%
b 63% 37 %
c
conjugate phases conjugate solution h
34-35 %
Critical solution temperature
06/09/11
Part I
One phase
h
50 -
Page 16 of 68
c tie line
conjugate solution
Two phases
0
11%
63%
100
: 20 50% tie
line bimodal 8.4 72.2 %w/w
500
100 = 50%
500 = 250
X
500-X
20 100 8.4
x
8.4 x/100
20 100 72.2
500-x 72.2(500-x)/100
06/09/11
Part I
(72.2(500-x)/100)+(8.4x/100) =
X
Page 17 of 68
250
174
174
500-174
=326
100
8.4
174 8.4x174/100 = 1
250-15 =
235
2
curve Blinding
Salting out
3
06/09/11
Part I
Page 18 of 68
100% B
100% A
100% C
BC AC
A
06/09/11
Part I
Page 19 of 68
3 2
-benzene alcohol 3
alcohol benzene benzene
06/09/11
Part I
Page 20 of 68
1.2
Partition
(Phase Equibria and the Phase Rule)

(Component)
F = CP+2
F = Degree of freedom
C = Component
P = Phase

P(mmHg)
A
R
P1
E
Liquid
P2
4.58
Gas
Solid
C
0.098
T2 T1
T(C )
1 phase :

, , D 2(F
= C-B + 2 = 1-1 +2 = 2) (bivarint,F = 2) 2
P2 T2
06/09/11
Part I
Page 21 of 68
2 phase :
2 ,
,
AO BO CO
E OA (F = C B + 2 = 1 2 + 2 =
1) ( univariant,F = 1) P1 T1
E
3 phase :
3 -- O
0 (F = C P + 2 = 1 3 + 2 = 0)
(invariant,F=0)
O

1. +
2. +
3. + +
4. + +
2 (Binary System)

2
g b h c : f bimodal curve 2
50oC 100%
b 2
11%
50o 2
C 63%
bc
2 tie line
2 (base line) tie line def 2
11% 89%
b 63%
37% C
06/09/11
Part I
Page 22 of 68
(conjugate phases)
(conjugate solution) (consolute solution)

h 66.8C
34-35% (Critical
solution temperature) (upper consolute temperature)

T (C)
One phase
66.8 C
50 C
c Tie line
Conjugate solution
g
0
Two phases
11%
63%
100
%w/w of phenol in water
20oC 50 % tie line

bimodal 8.4 72.2%w/w
500
100 g
=
50%
500 g
=
250 g
=
Xg

=
500 x g
06/09/11
Part I
20C 100 g
X g
20C 100 g
500 - X g
(8.4X/100) + (72.2(500-X)/100)
100 g
174 g
Page 23 of 68
8.4 g
(8.4X/100) g
72.2 g
(72.2(500-X)/100) g
= 250
X
= 174 g
= 174 g
= 500 174 g = 326 g
= 8.4 g
= 8.4 x 174/100 g = 15 g
= 250 15 = 235 g
2
bimodal
curve
blinding
2
salting out

2 (aniline), Carbondisulfide-methyl alcohol,Isopentane-Phenol,Methy alcoholCyclohexene,Isobutyl alcohol

(lower consolute temperature)
2
T (C)
T
Upper
CST
T ( C)
(C)
Salti
ngBlind
ing
06/09/11
%w/w of Phenol
in water
X
Low
er
%w/w of Nicotine
in water
Lower consolute
temperature
%w/w of TEA
in water
Part I
Page 24 of 68
3 (Ternary
System)
3 1 F = C P +
2 = 3 1 + 2 = 4 2
2
2 3
3 100%
A,B C
100
%
100
%
100
%
1 (plotting on the side)
1. BC
AC A
2. AC
AB B
3. AB
BC C
06/09/11
Part I
Page 25 of 68
100%
B
40% B
100% A
30% A
100% C
2 (plotting on the
perpendicular) 100%
AB C,
3 BC A ,
3 CA B
100% B
40% A
40% B
100% A
100% C
3 2 A
C Benzene Benzene benzene
benzene benzene
benzene benzene
benzene

d tie line ef
e
f ef
06/09/11
Part I
Page 26 of 68
3(alcohol)
tie line
g h i
hi tie line tie line tie
line 2 (plait point)

2
(A C) a e h l m n I f c absolute curve bimodal curve
bimodal curve bimodal curve bimodal
curve B
C A
2

(temperature effect) 3

(solvent effect)
(cosolvent) (blending agent)
3

) bimodal
curve
06/09/11
Part I
Page 27 of 68
1.3
Buffer & Isotonicity
1.
2.
Electolyte
=
electrolyte non-electolyte
1. colligative :
-
-
-
-
* molarity
colligative
! electrolyte
Vant Hoff : - electrolyte nonelectrolyte . Electrolyte
- collection factor I colligative . Electrolyte . nonelectrolyte
-. ----- > nonelectrolyte: i=1
-----> electrolyte
: i
NaCl =2 , CaCl2 =3

1) Conc.
2) Salvation of hydration (.)
2.
-spacific resistance
cm
-spacific conductance
= cell 1 cm2 1
= = .cell 1 cm3
: mhos Siemens (S)

conc..
06/09/11
Part I
Page 28 of 68
-equivalent conductance () = . 1 g cell
1 cm
electrolyte
electrolyte
- electrolyte
06/09/11
electrolyte 100%
Part I
-
Page 29 of 68
electrolyte conc.~ 0
* Vant Hoff Arrhenius electrolyte
a c (
)
-.
-conc.
1
.
*
*. electrolyte ,
06/09/11
Part I
-
Page 30 of 68
electrolyte .
. ~0.02
Ex.
-
- 1) proton proton
2)
(Acid-base equilibrium)
- reverse reaction
06/09/11
Part I
Page 31 of 68
buffer
Buffer solution: pH
Henderson-Hasselbalch equation (buffer equation)
salt
- Weak acid + its salt: pH pKa log acid
- Weak base + its salt:
pOH pKb log
base
salt
pH pKw pKb log
base
salt
buffer pH 4 10
activity (a)
a = C ionic strength ()
pH pKa log
salt log
A
acid
univalent ion = 0.1 0.2

log A 0.5
polybasic acid
log A A(2n 1)
Buffer capacity (): buffer pH

B
gm-EqL / pH unit
pH
salt
- acid
pH
salt
- max: acid
= 1 pH = pKa buffer ([salt]+[acid])
2.3C

Ka H O
Ka H 3O
3
max = 0.576 C
- buffer pH pKa 1
buffer
1. (pKa = pH 1) pKa pH buffer
buffer capacity
salt
2. acid
salt
3. C ( acid
) C (0.05-0.5 M) (0.01-0.1)
4. pH buffer pH ()
06/09/11
Part I
Page 32 of 68
buffer pH 5.00 = 0.02

1. (pKa = pH 1)
Acetic acid
pKa = 4.76
salt
2. acid
pH pKa log
salt
acid
5.0 4.76 log
salt
acid
salt = 1.74
salt = 1.74 acid
acid
3. (C) buffer
2.3C

Ka H O
Ka H 3O
3
0.02 2.3C
(1.75 10 5 )(1 10 5 )
(1.75 10
C = 3.75 x 10-2 M
) 1 10 5
4. 2. 3.
C = salt + acid
3.75 x 10-2 = 1.74 acid + acid
-2
acid = 1.37 x 10 M
salt = 1.74 acid
= 2.38 x 10-2 M
Isotonic
Isosmotic solution NaCl 0.9%
isotonic
Hypertonic solution
NaCl 2.0%
hypertonic crenation
06/09/11
Part I
Page 33 of 68
Hypotonic solution
NaCl 0.2%
hypotonic hemolysis
Tonicity tonicity 2
1. sodium chloride -0.52o
1.1 Cryoscopic method (Tf 1%) 1%
Liso
: NaCl
0.52o
NaCl 1% atropine Hydrochloride
100 ml isotonic ( Tf 1% atropine HCl = 0.08 Tf 1%
NaCl = 0.58)
Tf 1% 1% atropine HCl solution
= 0.08
Tf 1%
= 0.52
= 0.52 0.08 = 0.44

Tf 1% NaCl 1%
= 0.58
10.44
NaCl
= 0.76%
0.58
atropine HCl 1.0 NaCl 0.76
100 ml isotonic
1.2 Sodium chloride Equivalent method (E) sodium chloride
1 (= 1 NaCl E )
: NaCl NaCl 0.9%
100 ml
ephedrine sulfate 1 (E = 0.23) 100
ml sodium chloride isotonic dextrose (E
= 0.16)
1 g
=
NaCl 0.23 g
NaCl =
0.9 0.23
= 0.67 g
NaCl 0.16 g =
dextrose 1 g
NaCl 0.67 g =
dextrose 100.16.67 = 4.19 g
ephedrine sulfate 1 g NaCl 0.67 g 100 ml
06/09/11
Part I
Page 34 of 68
2. isotonic
isotonic
2.1 White- Vincent Method: pH tonicity ( E
)
: NaCl 0.9% isotonic solution
V = W x E x 111.1 d
V = (ml) isotonic
W =
E = sodium chloride equivalence, 111.1 100/0.9
cocain HCl 1% (E = 0.16) 30 ml isotonic
Cocaine 1 g =
NaCl 0.16 g
Cocaine 0.3 g =
NaCl 0.048 g
NaCl 0.9 g
=
100 ml
NaCl 0.048 g = 5.3 ml
Cocaine HCl 0.3 g 5.3 ml
isotonic solution 30 ml
2.2 Sprowls Method: (V) Vincent
isotonic solution
V (ml) isotonic A
( 0.3 g)
: A g V ml; A g isotonic solution

Epinephrine HCl
0.5 % (V = 9.7)
Zinc sulfate
0.3 % (V = 5.0)
Sterile Preserved Water qs. 30 ml
Epinephrine 0.3 g 9.7 ml
Epinephrine 0.15 g 4.85 ml
Zinc Sulfate 0.3 g 5.0 ml
Zinc Sulfate 0.09 g 1.5 ml
06/09/11
Part I
Page 35 of 68
Epinephrine HCl 0.15 g Zinc Sulfate 0.09 g

6.35 ml 30 ml isotonic solution (
2% pH 5 Epinephrine pH 5)
** isotonic (IV),
(IT), (IM), (ID), (SC)
tonicity
tonicity
1 : NaCl
0.52 C ( isotonic
)
2 :
. Isotonic
. Isotonic

Cryoscopic medthod
Sodium chloride equivalent method
*.
*E=.g NaCl osmotic
-0.52 C
1 g
*isotonic soln: 0.9% NaCl
Vincent method
Sprowls medthod
V = WE111.1
*V = (ml)
**V = (ml) isotonic soln
1 g
isotonic sol
W = . g
E = NaCl equivalence
111.1 100/0.9
06/09/11
Part I
Page 36 of 68
Micrometrics
Comprehensive
1. x SD
2
1. (Normal distribution)
- Mean = Mode = Median
- SD x
2. log-normal
Number
Size (micrometer)
Plot Number of particle

log size (micrometer) Normal
curve
- Mean Normal... Arithmetic mean

- Mean log -normal Geometric mean
Phar tech
Number
Size (micrometer)
Cumerative fraction
Cumerative
fraction
(%)
Z-score
Z-score
Size (micrometer)
Size (micrometer)
06/09/11
Part I
Normal curve
Z-score
1
Log-normal
curve
Size (micrometer)
Z-score
Log Size (micrometer)
Page 37 of 68
x = size z = 0 ( x)
SD = ( x Z=1) ( x Z=0)
(Z 1 )
x = size z = 0
SD
-
Geometric SD (g) =
EXAMPLE
Z-score
Z-score
2
100 200 300 400 500 600
-1
micron
-1
-2
-2
-3
-3
100 200 300 400 500 600
Z-score
Z-score
micron
1
0
10
-1
100
1000
micron
0
-1
200
450
micron
-2
-2
-3
-3
!!
Cumerative
50%
16%
16%
50%
84%
Size (micrometer)
06/09/11
(%)
84%
Number
16%
fraction
50%
Size (micrometer)
84%
Part I
Cumerative
fraction
Page 38 of 68
(%)
84%
50%
16%
1.29
1.84
2.61
Log size (micrometer)
2.
1.direct method
- optical microscope 1 m
- electron microscope 0.01 m
2. / sieving
:: :
=
: fibrous
3. (Sedimentation) ::
(settling velocity, v)
(spherical particles)
DP =
DL =
L =
V =
equivalent diameter, a =
Andreasen apparatus
06/09/11
18 L v
DP DL g
Part I
Page 39 of 68
4. (Electrical Sensing Techniques)

5. (Optical Techniques)
3.
-

:: Cutting () , Compression () ,Impact () , Attrition ()
Jum***
- F (bioavailability)
-
-
-
-
JUM!!!!
1.Tritulation
2.Pulverization by
intervention
- polymorph

-
-
- Wettability

Interventing agent
Acetone, Alcohol

camphor , iodine
3.Levigation
levigating agent

(Slab & Spatula)
glycerin , mineral oil
Jum****
smooth paste

slab spatula

1.Hammer mill****
2.Ball mill****
3.Fluid energy mill****
4.Cutting mill.. Fibrous material Cutting (Shearing action)
5.Disc mill. Disc 2 At Cut
6.Roller mill.. Roller 2-5 v Ointment, Paste Com (crushing)
7.Oscilating Granulator
06/09/11
06/09/11
(hammer)

,
- Attrition ()**Impact ()
- rotor
-
- hammer
-

-
-
-
-

-
- !!!
- abrasive material!!!
- Eff
Hammer mill
Fluid energy mill
- abrasive material!!!
-
- soft material ( )
-
-
-
-
- (SD )
- heat labile substance
Fluidization

attrition impact
- At,Im JUM!!
- At,Im JUM!!
Ball mill
Part I
Page 40 of 68
Part I
Page 41 of 68
4.
1. : Angle of repose ()
-
- ..
2.Density
Bulk density =
True density =
3. &

Kaolin Deform
Na2CO3 Dilatant

QUIZ

Rx
1)
2)
3)
4)
5)
06/09/11
Zinc oxide
Simple ointment
Color
Trituration
Pulverization
Levigation
Beaker method
Nascent soap method
.g
...g
.
Part I
Page 42 of 68
Rheology
Comprehensive
1.
1.

2.
3. Dispersion system

JUM !!
2.
= 2
1. Newtonian system
-
dv

dr
Shearing stress F rate of shear G
- Shearing stress (F) = G

- , () =
- Shearing stress JUM!!!
rate of shear
G
Rheogram
Slope=
=Fluidity()
Shearingstress(F)
06/09/11
= centipoises cp
Part I
- ( JUM!!! )

Kinematic viscosity
= Kinematic viscosity

r
(r) = Relative
viscosity
SP
Specific viscosity
=k
(SP)
- Viscosity number
Reduce viscosity
Page 43 of 68
stroke(s)
centistroke (cs)

Newtonian

!!
- SP
f(x)
[]=intrinsic
viscosity
C
[] = KMa ()
-
-K a
JUM!! New Benzene Glycerin Acetone Alcohol Water

Diluted deflocculated suspension ( < 10%)
2. Non - newtonian system
-
- 2

06/09/11
06/09/11
2.Pseudoplastic flow
JUM!!!!
1.
MC,sodium
carboxymetyl cellulose
2. Gum
tragacanth, acacia
3.
JUM!!!!
1.

Floc
2.Emulsion
3.Suspension C
4.Paste
5.Jelly ,
6.
1.Plastic flow
= Yield value (f) dyne/cm2

Shearing stress (F)
Shearing stress (F)
-
(Apparent viscosity) 2
1. Slope
2. FN = G
log G = N logF - log
N = 1 . Newtonian
N > 1 . Pseudoplastic
N < 1. Dilatant
( )
- Slope
= Mobility ( Fluidity )
- 1/Slope
= Plastic viscosity (U)
- F force of flocculation
( )
N
1.N
2. =
-Plot log G , log F
ZONE
- Yield value G F
- Shearing st > Yield
Floc Floc

-
-

-G
F
- G F
- (Shear thinning system)****
- Yield value
-
- G
ZONE
-
-
(rate of
shear )
- Shearing
stress Yield value
Part I
Page 44 of 68
06/09/11
1.Suspension
( 50%)
-
3.Dilatant flow
JUM!!!
- Pseudoplastic flow
-
(Shear thickening system)****
- Yield value
-
- F
Shearing stress (F)
ZONE
-
( )

- Rate of shear

ZONE
-
( )
Part I
Page 45 of 68
Part I
Page 46 of 68
(Thixotropic flow)
Negative Thixotropic Antithixotropic
-

- Plastic
Pseudoplastic
- Plastic flow + thixotropy !!!!!!
bentonite magma, veegum, kaolin
suspension , petrolatum
- Pseudoplastic flow + thixotropy !!! SCMC
-
- Thixotropic
-
(1-10%)
floccules Magnesium magma
rate of shear > 30 s -1 (
Thixotropic)
-
( )
-
( )
-
F
-
gel
-

gel
(gel to sol)

-

06/09/11
-
-

gel (sol to gel)

-
Part I
Thixotropy
Suspension Thixotropy

Page 47 of 68

(gel to sol)

emulsion ,suspension ,ointment ,cream ,lotion
suspension depot IM
(Bulges) (Spurs) (Jum!! )
Bentonite gel (JUM!!!)

1.Bulges

(
)
2.Spurs
Procaine penicillin gel (JUM!!!)
(
)
Rheopexy
(T)
Electrolyte
pH
Other
06/09/11
(fluidity )
Type , C electrolyte
-C
(fluidity )
pH (pH 6-8)
pH
, polyhydroxy glycerin ,propylene glycol
Part I
Page 48 of 68
3.
3
1.Capillary viscoometer
2
Oswald aisccometer capillaary
(Newwtonian)
2.Fallling sphere
viscoometer
(Newwtonian)
V 1/
3.Rotational cylinnder viscom

meter (Non--newtonian))
3.1 CCup & Bob viscometer
v
3.2 Cone & Plate viscoometer
a.Stoormer viscom
meter

Cup & Bob JUM!!!
1) Rate of sheear
plug
flow
2)
3)
4) T
::
JJUM!!!
::
b.Broookfield visccometer
, > 30
::
,
sheear rate
JUM!!!
c.Rottovisco viscometer ::

d.MaacMichael visscometer
ccup &
bob plug flow
sheear stress JUM!!!
06/09/11
Part I

1. rate of shear shear stress
. Newtonian
. Plastic . Pseudoplestic . Dilatant . Thixotropy
2. non-newtonian yield value
. Pseudoplestic . Dilantant . Thixotropy
. Plastic .
3. plastic
. deflocculated suspension
Page 49 of 68
. flocculeted suspension
. deflocculeted suspension
. flocculeted suspension
.

4. shear-thinning system
. glycerin . polyethlene glycol . minerol oil . 2% sodium carboxymethylcellulose . 5% bentonite
5.
. newtonian . bingham badies . pseudoplastic . dilatant . thixotropy
6. falling ball viscometer
.
. non-newtonian
.
. newtonian
.
7. 2
. Falling sphere viscometer . Cup & bob viscometer
. Cone & plate viscometer . Stormer viscometer
. Ostwald viscometer
8. Newtonian
. ChloroformWaterBP
.CarbomerJellyyieldvalue .
BenzoylPeroxideCreamBP
. LiquidparaffinoralEmulsionBP. Milkofmagnesia

9. Specificviscosity
. Newtonianflow.Plasticflow.Pseudoplasticflow .Dilatantflow.Creepflow
10.Topicalsteroid
.Pseudoplasticflowwiththixotropy.Dilantantflowwiththixotropy
.Pseudoplasticflow.Newtonianflow.Antithixotropy
1. 2. 3. 4. 5. 6. 7. 8. 9. 10.
06/09/11
Part I
Page 50 of 68
1.7 Pharmaceutical Necessities
1.
2.
1. (Coloring agents, Colorants)
1) USFDA 3
1.1 FD&C
1.2 D&C
1.3 External D&C
(mucous membrane)
2) 3
2.1 Dyes
2.2 Pigment
2.3 Lakes organic pigment dye absorptive diluents CaCl2, ZnO
3)
3.1 Azo group (N=N)
- Sudan III
- Sunset yellow, Tartrazine, Ponceu 4R sulfonic acid Na sulfonic acid
alkaline earth
3.2 Triphenylmethane (Rosaniline) phenyl group 3 2
- Basic dyestuffs side chain amine gentian violet, crystal violet, malachite green
- Acid dyestuffs side chain sulfonic acid Na
3.3 Xanthenes 2 tautomeric forms pH
- quinoid form (xanthenes type)
- phenolic form (fluoran type)
3.4 Thiazine Methylene blue
3.5 Acridine Acriflavine
3.6 Quinolines D&C yellow
06/09/11
Part I
Page 51 of 68
1) Stability Azo Triphenylmethane reduction

2) Incompatibility acid dyes basic dyes
cationic surfactant
pH
- lemon syrup
- basic dye
3) Solubility
- form salt alkali (Na, K, NH4)
- form salt alkali earth (Ba, Ca, Sr)
4) Safety
- FDA (certified colors)
amaranth (FD&C No.2)
- tartrazine
5) Quantity, Dosage form

-
Solutions 0.0005-0.001%
Emulsions 0.001-0.005%
Suspensions 0.001-0.005% lake
- Powder 0.1%
6) Patient, Acceptant
2. (Flavoring agents, Flavorants)
1) hydrogen ion H+
2) polyhydroxyl compounds sucrose, sorbital OH- group
3) NH4Cl, NaCl
NH4Br, NaBr (MW 102.9)
4)
- high MW salts MgSO4(MW 246.5), Phenobarbital sodium (MW 254.24)
- Free base amine
- Nitrogen containing compounds
- polyhydroxyl compounds MW >300
- halogenated substances chloral hydrate
- plant alkaloids quinine
06/09/11
Part I
Page 52 of 68
1) Blending

citric acid
2) Overshadowing Cod liver oil
methyl salicylate glycyrrhiza
3) Physical
-
chloramphenicol ( 1:400)
chloramphenicol palmitate (palmitate ester 1: >1000 )

acacia syrup
coated tablet, capsule, effervescent powder
4) Chemical ion exchange resin
5) Physiological menthol, peppermint

mannitol
1)
2)
3)
-
-
-
4)
- peppermint
- glycyrrhiza -
5) vanillin aqueous penicillin sulfonamides
6)
7)
8) sorbital,
saccharin
06/09/11
Part I
Page 53 of 68
3. (Preservatives)
1)
2)
3) p H
4)
5)
6)
7)
1)
benzoic acid, boric acid, phenol, alkyl esters of p-hydroxybenzoic acid
(methylparaben, butylparaben)
2) benzyl alcohol, chlorobutanol
3) thimeroal, phenylmercuric nitrate(PMN), phenylmercuric acetate(PMA)
4) quaternary ammonium benzalkonium chloride
1) pH

(dissociation constant) pH
-
pH
pH
2) (Distribution coefficient, Ko/w)

3)
-
surfactant, gum polymer
Methylparaben, propylparaben, benzalkonium chloride, dehydroacetic acid
4) methylparaben + propylparaben

5)
-
06/09/11
aqueous preparations syrup, emulsion, suspension
Part I
Page 54 of 68
, large volume parietal

500 ml , hydro-alcoholic preparation alcohol

- pH alcohol > 15%
- pH alcohol > 18%
4. (Antioxidant)
oxidation

3
1) True antioxidant oxidation free radical
(chain reaction)
Butylated hydroxyl anisole (BHA), Butylated hydroxyl toluene (BHT), Tocopherols (vitamin E)
2) Reducing agent standard oxidation potential (E)
( E E )
ascorbic acid, sodium sulfite, sodium metabisulfite, thioglycollic acid
3) (Synergist) chelating agents (ligand) metal ion (
oxidation ) metal-ligand complex
Ethylene diamine tetraacetic acid (EDTA), citric acid, tartaric acid
06/09/11
Part I
Page 55 of 68
Polymorhism
Polymorphism
Polymorphism and Eutectics
Polymorhism
Polymorphism

1.
(solubility and dissolution rate)
polymorph

bioavailability polymorph
Enantiotropic: 1

Monotropic:
Polymorhism
2.
(stability and manifacture ability)
Polymorph
Polymorph

Amorphous form
wet granulation
Polymorhism
polymorph
Recrystallization:

Polymorph
: amorphous
Polymorph

Polymorph
06/09/11
:
mobility

(%RH):
mobility degree of freedom

Part I
Eutectics
Page 56 of 68
Eutectic
Eutectic
Eutectic point
1

Eutectic point:

Eutectic mixture

Eutectic
Eutectic mixture
Eutectic mixture
- Aspirin
- Camphor
- Lidocaine
- Phenocaine
- Prilocaine
- Salicylic acid
Eutectic
- Antipyrine
- Benzocaine
- Chloral hydrate
- Mentol
- Resorcinol
Salol and related compounds
Eutectic mixture

absorbent talc, starch, lactose, calcium
phosphate
Eutectic absorbent
Eutectic
Eutectic mixture

Menthol Testosterone

Lidocaine Prilocaine
69C 38C

06/09/11
Interfacial phenomena
( )
(interface): 2

surface
Part I
(surface tension, )
= fb/2L (dyne/cm)
fb: dS
L:
dS
Page 57 of 68

cohesive force
adhesive force
: / dyne/cm, mN/m

= cohesive force - adhesive force

w = A
= w/A (ergs/cm2 = dyne/cm)
w: (ergs)
A: (cm2)
= 2L s, s:
P = 2 /r
= r P/2 (dyne/cm)
P:
r:
06/09/11
polarity:
:
Part I
Page 58 of 68
1. Capillary rise method
2. The DuNouy Ring method

surface tension interface tension
= (dyne) correction factor
2
Spreading
work of adhesion work of cohesion
06/09/11
surface tension
: = rhg
3. Drop weight methods

4. Maximum pressure method
5. Pendent drop method
5. Sessile drop method
6. Wilhemy Plate method
Work of adhesion (Wa)

Wa = A + B AB
Part I
Work of cohesion (Wc)

Wc = 2 A
Page 59 of 68

Work of adhesion > Work of cohesion
Spreading coefficient (S) = Wa Wc
= B (A - AB)
S
Adsorption
surfactants ()
Adsorption():

Absorption ():
1. ionic surfactant:
- anionic surfactant: soap (R-COO-), alkyl sulfate
(R-OSO3 -)
- cationic surfactant:
toxic alkyl ammonium (R-NH3+)
- zwitterionic surfactant: lecithin
2. nonionic surfactant:
span, tween
HLB
(Hydrophillic-Lipophilic Balance)
Adsorption at solid interface
HLB
HLB
06/09/11
1. solid-gas interface
2. solid-liquid interface
Part I
1. solid-gas interface
Page 60 of 68
Type 2: non porous solid, multi layer
Adsorption isotherm
Type1: non porous solid, monolayer
Type 3: non porous solid, multi layer
Type 4: porous solid, multi layer
gas
2. solid-liquid interface
Electrical properties at interface
adsorbent charcoal, clay

Langmuir equation:
slope =
b
c
Potential determinating ions
counterion
06/09/11
Part I
Page 61 of 68
aa: solid potential determining ion

bb: shear plane

cc:

06/09/11
Part I
Page 62 of 68
Polymorphism and Eutectics

Polymorphism: (crystalline form)
2

polymorph polymorph
enantiotropic
polymorph
monotropic
polymorphic

(Polymorphism)
1. (solubility and dissolution rate)
polymorph
bioavailability
2. (stability and manifacture ability)

Polymorph Polymorph
Polymorph

amorphous
wet granulation

polymorph
- Recrystallization: Polymorph

Polymorph
06/09/11
Part I
Page 63 of 68
- : amorphous
Polymorph Polymorph
Polymorph
Polymorph
- : mobility

- (%RH): mobility
degree of freedom
polymorph
Eutectics
Eutectics 1

Eutectic point
Eutectic mixture
06/09/11
Part I
Page 64 of 68
Eutectic mixture
-Acetaminophen
-Thymol
-Aspirin
- Antipyrine
-Camphor
- Benzocaine
-Lidocaine
- Chloral hydrate
-Phenocaine
- Mentol
-Prilocaine
- Resorcinol
-Salicylic acid
- Salol and related compounds
Eutectic mixture
Eutectic mixture
-
- absorbent talc, starch, lactose, calcium phosphate
- Eutectic absorbent
Eutectic mixture
Menthol Testosterone

Lidocaine Prilocaine
69C 38C

06/09/11
Part I
Page 65 of 68
Interfacial phenomena ()
(interface): 2
(surface tension, ):
cohesive force adhesive force / dyne/cm, mN/m
= cohesive force - adhesive force

= fb/2L (dyne/cm)
fb:
L:
d
S

w = A
= w/A (ergs/cm2 = dyne/cm)

A:

P = 2 /r
= r P/2 (dyne/cm)
w: (ergs)
(cm2)
= 2L s, s:
P:
r:
- polarity:
- :
1. Capillary rise method: surface tension
= rhg
2. The DuNouy Ring method: surface tension interface tension
06/09/11
Part I
Page 66 of 68
= (dyne) correction factor

2
3. Drop weight methods
4. Maximum pressure method
5. Pendent drop method
5. Sessile drop method
6. Wilhemy Plate method
Spreading:
Work
of adhesion work of cohesion
Work of adhesion (Wa): Work of cohesion (Wc):
Wa = A + B AB
Wc = 2 A
Work of adhesion > Work of cohesion

Spreading coefficient (S) = Wa Wc
= B (A AB)
S
Adsorption (): Absorption ()
Adsorption at liquid interface

positive adsorption:
negative adsorption:
surfactants ()
06/09/11
Part I
Page 67 of 68
1. ionic surfactant:
- anionic surfactant: soap (R-COO-), alkyl sulfate(R-OSO3 -)
- cationic surfactant: toxic alkyl
ammonium (R-NH3+)
- zwitterionic surfactant: lecithin
2. nonionic surfactant: polyoxyetylene
(span), polyoxyetylene derivative (tween)
HLB (Hydrophillic-Lipophilic Balance): HLB
HLB
Adsorption at solid interface
1. solid-gas interface: gas
Adsorption isotherm
type1: non porous solid, monolayer
type2: non porous solid, multi-layer
type3: non porous solid, multi layer

gas
06/09/11
type4: porous solid, multi layer
Part I
Page 68 of 68
2. solid-liquid interface: adsorbent charcoal, clay

Langmuir equation: c
Y
1
c
bYm Ym
c: adsorbate
Ym: adsorption carpacity
slope =
1
Ym
Electrical properties at interface

1.
2.
3. dielectric constant
Electric double layer
a
Potential determinating ions

counter ion
aa: solid potential determining ion

bb: shear plane

cc:
06/09/11
PART II: Pharmaceutical

Dosage Forms
Solutions
Colloids
Suspensions
Emulsions
Semisolid dosage forms
Suppositories
Tablets
Modified Release Dosage Forms
Powders & Granules
Capsules
Sterile Dosage Forms
Aerosols
Part II
For Comprehensive Examination
Page 1 of 126
(solution)
Aromaticwater
Spirit
Syrup
Elixir
Tincture
/

/

(solution)

1

Solution

paraben
nonmedicated syrup
sulfites,ascorbicacid
aceticacidanditssalt
surfactants
(solutionpreparedbysimple
solution)
(solutionpreparedby
chemicalreaction)
(solutionpreparedby
simplesolutionwithsterilization)
(solutionpreparedby
extraction)
(masterformula)

workingformula,approximatevolume
,vehiclevolume

09/06/11
Part II
aliquot
Paediatric ferroussulphate oralsolutionBP

12g
Working
formula
0.6g
App.Vol
Ferrous
sulphate
Ascorbicacid
2g
0.1g
0.05g
Orangesyrup
100ml
5ml
5ml
Double
strength
chloroform
water
Water
sufficientto
produce
500ml
25ml
25ml
1000ml
50ml
50ml
x19.65ml15ml
09/06/11
Page 2 of 126
0.3g
aliquot ascorbicacid doublestrength

chloroformwater ascorbicacid1:20
ascorbicacid0.1g toploading(
=0.5g)
1.Multiplefactor =5
2. ascorbicacid=0.5g
3. ascorbicacid0.5g DSchloroformwater
50ml( ascorbicacid1:20)
4. aliquotpart=10ml( totaldilution/multiple
factor)
5. 4 10ml ascorbicacid0.1g
Part II
Page 3 of 126
2.1

Solution
Aromatic water
Spirit
Syrup
Elixir
Tincture
(solution)
1

ethanol, glycerin, propylene
glycol
Inorganic salt organic

compound
Alcohol (ethyl
Organic compound
preservative action
Tannin,phenol boric acid
alcohol)
Glycerin(glycerol)
preservative (45%v/v)
Propylene glycol
organic compound
preservative
09/06/11
Part II
Page 4 of 126

paraben
nonmedicated syrup
sulfites , ascorbic acid
acetic acid and its salt
surfactants

Alcohol
15 %

Benzoic acid and its salt
0.1-0.3%

Chloroform
0.25%
mixture,extracts
Methyl paraben
0.2%
Paraben concentrate
1%
paraben concentrate methyl paraben

10%
Propyl paraben
2%
Propylene glycol to
100%
1. (solution prepared by simple solution)

2. (solution prepared by chemical reaction)

2

3. (solution prepared by simple solution with
sterilization) ophthalmic solution
09/06/11
Part II
Page 5 of 126
4. (solution prepared by extraction)

1. (master formula)
2. working formula , approximate volume , vehicle volume

3.
4.
5.
Paediatric ferrous sulphate oral solution BP

Rx
Ferrous sulphate
12 g
active ingredient
Ascorbic acid
2g
antioxidant
Orange syrup
100 ml
sweetening agent
Double strength chloroform water 500 ml
Water sufficient to produce
vehicle
1000 ml
Working formula
App. Vol
Ferrous sulphate
12 g
0.6 g
0.3 g
Ascorbic acid
2g
0.1 g
0.05 g
Orange syrup
100 ml
5 ml
5 ml
Double strength chloroform water
500 ml
25 ml
25 ml
Water sufficient to produce
1000 ml
50 ml
50 ml
x 19.65 ml 15 ml
: ascorbic acid double-strength chloroform water
ferrous sulphate orange syrup
09/06/11
Part II
Page 6 of 126
aliquot ascorbic acid double-strength chloroform water

ascorbic acid 1:20 ascorbic acid 0.1 g top loading( =
0.5 g)
1. Multiple factor = 5
2. ascorbic acid = 0.5 g
3. ascorbic acid 0.5 g DS chloroform water 50 ml(
ascorbic acid 1:20)
4. aliquot part=10 ml( total dilution/multiple factor)
5. 4 10 ml ascorbic acid 0.1 g
09/06/11
Part II
Page 7 of 126
(Aromatic water)
(volatile oil)

- volatile oil aromatic or volatile substance

- purified water
official 4
1. (distillation method)

(distillation) (excess oil)

distillation distillate

2. (solution method) (
) 15 12
(coalesce)
(settle)

3. (distributing agent) (alternative solution method)
purified talc, purified silicious earth
10

4. (dilution method) (official BP) concentrated aromatic water (

alcohol alcohol 50-55%) purified
water 39 ( alcohol 1.5%) alcohol
alcohol
09/06/11
Part II
Page 8 of 126
official nontoxic-nonionic surfactant Tween ( Polysorbate )

( solubilization agent )

tight light resistant container

Rose Water perfume
Hamamelis Water perfume astringent aftershave lotion
Cinnamon Water carminative vehicle Chalk Mixture
Peppermint Water NF
Rx Peppermint Oil
2 ml
Purified Water to
100 ml
Talc.
15 g
Peppermint Oil Talc. 15 Talc.

1000 . 10

09/06/11
Part II
Page 9 of 126
(Elixirs)

2
1.non-medicaed elixirs (alc+ ), ,

2.medicated elixirs
1. alc hydroalcoholic solution

elixir
2.
+alc (Hydroalcoholic solution)alc
alc medicate elixir alc 5-15%

Paediatric preparation alc 5%
Non-medicated elixir alc
cosolvent PEG 400, propylene glycol, glycerin

3. Sucrose
4.
5.
6.
2
1. ( Simple solution )

2. / 2 ( The Admixture of two or

more liquid ingredient ) /
alcohol
hydroalcoholic solution
alcohol elixir
Iso-alcoholic Elixir
low alcoholic elixir ( Alcohol 9 % v/v ) high alcoholic elixir ( alcohol
75% v/v ) alcohol
09/06/11
Part II
Page 10 of 126
Iso-alcoholic elixir
Iso-alcoholic elixir alcohol 40 %
9
35
40
75
31
66
Iso-alcoholic elixir 66 ml high alcoholic elixir
31
ml
Iso-alcoholic elixir 100ml high alcoholic elixir
(31x100)/66 = 47
ml
Iso-alcoholic elixir 66 ml low alcoholic elixir
35
ml
Iso-alcoholic elixir 100ml low alcoholic elixir
(35x100)/66 = 53
ml
Iso-alcoholic elixir alcohol 40 %v/v high alcoholic elixir 47

ml low alcoholic elixir 53 ml
09/06/11
Part II
Page 11 of 126

Syrups( )

FlavoringSyrup vehicle
MedicatedSyrup

1. ( Medicationagent)

Cosolvent
2. ( Sweeteningagent)
2.1. ( Sucrose,dextrose)
SyrupUSP( simplesyrup) 85%w/v,64.74w/v
SyrupBP66.7w/v
2.2. ( Sorbitol ,Glycerine )
2.3. ( Saccharin,Aspartam ,Xylitol

3.
Benzoic acid
0.1-0.2 %
Paraben Concentrate 0.1 %
Alcohol 15-20 %
09/06/11

3.

Rx

5

3
Glycerin
15
Sucrose
25
Ethanol 95 %
q.s.
Purified water q.s. 100 ml
ml
ml
ml
g

Part II

3.
1. freewater
simplesyrup sucrose85%w/v

Syrup100ml sucrose85g
( simplesyrup =1.313
simplesyrup100ml 131.3g )

3. ( )
2. Preservative
Sucrose 85 g Preserve
46.3 ml
Sucrose 1 g Preserve 46.3 / 85 = 0.54 ml
Page 12 of 126

3. ( )
1. freewater
Simplesyrup 131.3g 131.385=46.3ml
46.3g
simplesyrup 100ml sucrose 10046.3=
53.7ml

3. ( )
2. Preservative
Sucrose 85 g
53.7 ml
Sucrose 1 g
Preserves
0.63 ml
Sucrose 25 g
Preserve 0.63 x 25 = 15.75 ml
sucrose 25 g preservative 25 x 0.54 =

13.5 ml

3. ( )
2. Preservative
= 5+3 = 8 ml
Glycerin 1 ml preserve
1
ml
Glycerin 15 ml preserve
15
ml
Glycerin
Preserve 15 ml
09/06/11

3. ( )
2. Preservative
preservative = 13.5 +
15.75 + 8 + 30 = 67.25
free water 100 -67.25 = 32.75 ml
Preservative
alcohol
18 %
Alcohol ( 100 % ) 0.18 x 32.75 = 5.9 ml
Part II

3. ( )
2. Preservative
alcohol 95 % 5.9/0.95 = 6.21 ml

Alcohol 95 % 6.21 ml

Page 13 of 126

4.

5.

6. ( pH57)
7. Thickeness ,solubilizing agent
1.
sucrose sucrose

## syrup
T
## syrup syrup
caramelization
sucrose
2.

sucrose

syrup
3. sucrose
tincture,
sucrose
4. Percolation
syrup Percolator
09/06/11
Part II
Page 14 of 126
( Syrup )

2
1. ( Flavoring syrup ,Flavored syrup , non-medicated syrup )
2. ( Medicated syrup )
alcohol
1.
( CPM , Dextromethorphan ) (
Paracetamol ,Ibuprofen ) ( Co-solvent )

form complex
2.
a. Sucrose , Dextrose ( )
Syrup BP Sucrose 66.7 % w/w
Syrup USP = simple syrup sucrose 85 % w/v 64.74 % w/w
Syrup BP Syrup USP Self preservative
b. sorbital , glycerin
c. ( Artificial sweeteners ) saccharin , aspartame
3.
, self Preservative ,
Preservative benzoic acid 0.1-0.2 % sodium
benzoate 0.1-0.2 % Paraben concentrate 1.0 % Alcohol 15-20%
4.
5. ( )
6. ( reverse osmotic pH 5-7 )
7. cosolvent ,solubilizers , Thickness ( Na alginate 2.5 % , Na CMC 1.5 % ) ,
Stabilizers ( antioxidant )
09/06/11
Part II
Page 15 of 126
Free water ( )
- free water Syrup USP ( Simple syrup ) specific gravity =
1.313 ( Syrup USP 1 ml 1.313 g )
Syrup USP Sucrose 85 % w/v
Specific gravity Syrup 100 ml 100 x 1.313 = 131.3 g
= .. .. Sucrose
= 131.3 85
= 46.3 g 46.3 ml
Sucrose ( 1g : 0.5 ml ) Sucrose 1 g 0.5
ml sucrose 85 g sucrose 85 g 85x0.5 = 42.5 g
42.5 ml
free water = 46.3-42.5 = 3.8 g

Rx
ml
ml
Glycerin
15
ml
Sucrose
25
Ethanol 95 %
q.s.
Purified water q.s.
100
ml
1. free water
simple syrup sucrose 85% w/v Syrup 100 ml sucrose 85 g
( simple syrup = 1.313 simple syrup 100 ml 131.3 g )
Simple syrup 131.3 g
131.3-85 = 46.3 ml 46.3 g
simple syrup 100
sucrose 100-46.3 = 53.7 ml
ml
2. Preservative
2.1.
Sucrose
85 g Preservative
46.3 ml
Sucrose1 g Preservative 46.3 / 85 = 0.54 ml

sucrose 25 g preservative 25 x 0.54 = 13.5 ml
09/06/11
Part II
2.2.
Page 16 of 126
Sucrose 85 g 53.7 ml
Sucrose 1 g
Preserves
0.63 ml
Sucrose 25 g Preserve 0.63 x 25 = 15.75 ml

2.3. = 5+3 = 8 ml
2.4. Glycerin
Glycerin
ml
preservative
ml
15
ml
preservative
15
ml
Glycerin Preserve
15 ml
2.5. preservative = 13.5 + 15.75 + 8 + 30 = 67.25
free water 100 -67.25 = 32.75 ml
2.6. Preservative alcohol 18 %
Alcohol ( 100 % ) 0.18 x 32.75 = 5.9 ml
2.7. alcohol 95 % 5.9/0.95 = 6.21 ml
Alcohol 95 % 6.21 ml
free water sucrose substance 65 % w/v alcohol

Preservative 18 % Alcohol ml
Syrup USP ( 85%w/v ) Self preservative
Sucrose 85 g syrup 100 ml 85 % w/v syrup 100 ml sucrose 85 g
Sucrose 65 g 85 % w/v = ( 65x100 ) / 85 = 76.5 ml
Free water = 100 76.5 = 23.5 ml
alcohol = ( 18 x 23.5 ) /100 = 4.23 ml
**** simple syrup alcohol 10 % *****
4
1.
sucrose
sucrose syrup
syrup T
syrup syrup
caramelization sucrose
09/06/11
Part II
2.
Page 17 of 126
sucrose

syrup
3.
sucrose sucrose
tincture Fluidextracts
4.
Percolation sucrose Percolator
percolate
09/06/11
Part II
Page 18 of 126
(Tincture)
alc alc
crude drug 1
compound
2
1. potent tincture potent drug tincture 100 ml potent drug
crude drug 10 g 10% tincture
2. non-potent tincture non-potent drug tincture 100 ml
non-potent drug crude drug 20 g 20% tincture
50% tincture tincture 100 ml 50 g
3
1. Maceration (process M)
USP tincture 1000 ml
- crude drug solvent 750 ml 3
- 1000 ml
BP crude drug menstruum 7 (
14 )
Compound Benzoin Tincture USP

Benzoin (in moderately corse powder)
Aloe (in moderately corse powder)
100 g
20
Storax
80
Toru Balsam
40
To make
1000 ml
2. Percolation (process P)
1. crude drug percolator
09/06/11
menstruum
Part II
Page 19 of 126
2. crude drug crude drug menstruum

crude drug
crude drug percolator
menstruum
3. crude drug percolator crude drug
percolator
menstruum percolator
2/3 3/4 percolator
menstruum crude drug
(lower orifice) menstruum percolator

4. crude drug 1-24
menstruum crude drug
5. percolate menstruum
menstruum
percolate
slow rate
1 ml/min
moderately rate
1-3 ml/min
rapidly rate
3-5 ml/min
tincture percolation USP ( 1000 ml)

1. crude drug menstruum 15
2. crude drug percolator menstruum crude drug
3. crude drug 24
4. percolate slowly rate
tincture percolation BP
1. crude drug 4
2. percolator
09/06/11
Part II
Page 20 of 126
3. percolate 3/4
4. percolate
5. menstruum
Belladonna tincture USP

Belladonna leaf (in moderately corse powder)
To make about
100 g
1000 ml
3. simple solution tincture
(Fluidextracts)
Fluidextractsg alcohol
ml Fluidextract crude
drug 1 (Fluidextracts potent drug 10 tincture)
Fluidextracts
()
percolation menstruum
Belladonna fluidextract
Belladonna leaf (in moderately corse powder)
To make about
09/06/11
1000 g
1000 ml
Part II
Page 21 of 126
( Spirits of Essence )
( Volatile substance ) alcohol
alcohol
tight container (
, , , gas ) light resistance container
- volatile aromatic substance

- Vehicle Alcohol Alcohol alcohol
(
Aromatic water )
-
4
1.
( Simple solution )
Alcohol alcohol
alcohol purified talcum
Camphor Spirit USP
2.
( Solution with maceration )

alcohol Pepermint Spirit USP
3.
( chemical reation )
aromatic ammonia spirit ammonium carbonate

NH4HCO3.NH2COONH4 + NH4OH 2(NH4)2CO3
4. ( distillation )
-
-
alcohol !!!!
09/06/11
09/06/11

-gum = (/)
. Acacia, tragacanth, guar gum
thickening agent, protective
colloid
-mucilage 2
gelatin, starch, agar
Cellulose derivative
(MC, CMC, HEC)
Mucilage
Mixture
1
-
2
1 freshly prepared
24 hr
2 recently prepared
2-3
-

-
hydroalcoholic
vehecle
-

bentonite,Veegum,
hectorite
-

MgSO4+NaOH= Mg(OH)2
-
- 2
Magma,Milk
2
- (Internal/Dispersed phase)
- (External/Continuous phase)
Colloidal dispersions = 1 nm-0.5 m 0.5 m
Colloidal Dispersion Dosage Forms

two phase gel
Magma
( organic gel/single
phase

gellies)
Inorganic Gel()
Part II
Page 22 of 126
09/06/11
-
(demulcent)
- suspending agent, emulsifier

Gel
, mucilage
1 freshly prepared
dose 2
2 recently prepared
1
14
brown mixture Al(OH)3 gel

Mixture
Dispersing agent
alcohol, glycerin
Acacia mucilage
(tragacanth
-/
MOM
- suspending agent
bentonite magma,
calamine lotion
mucilage
Magma,Milk
1.
disperse phase
2.
3.
Mucilage
Mucilage
Part II
Page 23 of 126
Part II
Gum
Acacia: alcohol
/
Tragacanth: 2
-tragacanthin30-40%
-bassorin 60-70%
Mucilaginous substances
Gelatin: (hydrolysis collagen)

2 A B
Starch: 2
-amylose 10-20%
-amylopectin 80-90%
Agar:
MC:

-MC 1/3
2/3
homogeneous
SCMC /
CMC,HEC
/
Magma
2
1. Simple hydration
bentonite,Veegum, hectorite
1.1.:

09/06/11
Page 24 of 126
1.2 :
2. Chemical reaction
MOM
Mixture 2
1.
(simple mixture)

2.(Suspension):

mixture
2
1.
: /
3/4

2. (solubilizing
agent) polysorbate(Tween )
alcohol
aqueous solution

Gel 2
1.
2.
Part II
Page 25 of 126
2.3 (Suspension)

(coarse dispersion)
0.5-5 m (aggregates of particle) 50 m

1.
2. vehicle
3.
4.
5.
6.
1. (Wetting)
(contact angle)
cos = (SV- SL) / LV

SV = SL + LV cos
SV =
SL =
LV =
=
alcohol, glycerine, propylene glycol, surfactants ( LV SL

) bentonite, tragacanth, acacia
2. (Particle particle interaction)
2 (attraction) van der waal force
(repulsion)
DLVO Theory ()
VT = VA + VR
2 Total energy of interaction (VT)
(VA) (VR)
(aggregation)
Flocculation floccules
Coagulation coagula
09/06/11
Part II
Flocculated system
-
-
-
- supernatant
- open packing
- redispersible
Page 26 of 126
Deflocculated system
-
-
-
- supernatant
- close packing
-non redispersible
3. (Rheology)
Newtonian flow
- shearing stress
- Deflocculated suspension < 10%
Plastic flow
-
- Flocculated suspension floccules

Pseudoplastic flow
- shearing stress
-
- suspension polymer Mw suspending agent
tragacanth, sodium alginate, methyl cellulose, sodium carboxy methyl cellulose
Dilatant flow
- shearing stress
-
- Deflocculated suspension >50%
Thixotropy
-
methylcellulose, acacia, bentonite, carbopol
4. (Crystal growth)
-
- (polymorph)
-
- polymer, gum, surfactant
-
- diffusion rate
09/06/11
Part II
Page 27 of 126
5. (sedimentation rate)
Stokes law
v = (cm/sec)
d = (cm)
p = (g/ml)
po= (g/ml)
g =
= (poise)
v
1.(d):
-
2. (p-po):
- vehicle
-
3. vehicle
- suspending agent
stokes law
-(0.5-2g/100ml)
-
1.
1.1 Sedimentation volume (F)
Hu Vu
Ho Vo
F = 0.5
F = 1.0
F = 1.5
1.2 Degree of flocculation ()

flocculation
F = Sedimentation volume flocculated suspention
F = Sedimentation volume Deflocculated suspention
09/06/11
Part II
Page 28 of 126
2. (redispersibility)
-
-
-
3. zeta potential
- zeta potential Sedimentation volume
- Electrophoresis (

)
4.
- , light
scattering
- aggregation Crystal growth
5.
- suspension
6. Temperature stress test
- Freeze and Thaw test
7.
8.
9. (shelf life)
- stability shelf life 90 %
1.
2. geometric dilution
3. Suspending agent : wetting agent vehicle
smooth paste
Suspending agent mucilage:
Suspending agent: wetting agent vehicle smooth
paste
4. vehicle vehicle vehicle
vehicle
5. 4 vehicle
6.
09/06/11
Part II
Page 29 of 126
2.4 Emulsion
2
(emulsifying agent emulsifier)
- Preservative Benzoic acid, Paraben concentrate

- Antioxidant Sodium sulfite, Ascorbic acid
- Sweetening agents Saccharin, Aspartame
-Flavoring agents Vanillin
- Coloring agents
Emulsifying agents
(Emulsifying agents)
()
emulsify emulsification
1.
2. (strong film)
3.
4. electrical double layer interface
1 (true emulsifying agent)
2-4 (auxiliary emulsifying agent)
09/06/11
Part II
Page 30 of 126
1. Natural emulsifying agents:

acacia, gelatin (type A, type B), lecithin, cholesterol,
egg yolk, tragacanth
2. Synthetic Emulsifying agents:

1.1 Anionic surfactants: Soap 3
- soap fatty acid akali monovalent soap
pH 10

- soap fatty acid di trivalent cation di/trivalent soap

- soap fatty acid organic amine amine soap
triethanolamine (TEA)

- Alkyl sulfate: ester fatty alcohol sulfuric acid sodium lauryl sulfate
1.2 Cationic surfactants: emulsifier disinfectant preservative

Cetrimide (weak emulsifier)
1.3 Non-ionic emulsifying agent: pH
Sorbitan (Span, Aracel), Polysorbate (Tween)
1.4 Ampoteric surfactants: lecithin
3. Finely divided solids: colloidal clay bentonite, veegum
4. Auxiliary emulsifying agents:
Agar, Methylcellulose, Pectin, Silica gel
emulsifier (Mixed Emulsifying Agents) HLB

09/06/11
Part II
Page 31 of 126
Hydrophile-Lipophile Balance: HLB system

non-ionic emulsion agents HLB
HLB (required HLB : RHLB) RHLB
o/w emulsion agent HLB =8-18 ()

w/o emulsion agent HLB = 3-6 ()
required HLB O/W Emulsion
Mineral oil
30%
Wool fat
2%
Stearyl alcohol
1.5%
Emulsifier
10%
Water
56.5%
1. required HLB oil phase

HLB
HLB
Mineral oil
30%
12
30/33.5
= 0.896
0.896 x 12 = 10.75
Wool fat
2%
10
2/33.5
= 0.060
0.060 x 10 = 0.597
Steryl alcohol
1.5%
14
1.5/33.5
= 0.045
0.045 x 14 = 0.627
33.5%
required HLB =
11.974
2. surfactants chemical type series

degree of saturation lipophilic component
span 80
Tween 80
HLB = 4.3
HLB = 15.0
Required HLB = 12
09/06/11
Part II
Page 32 of 126
span 80 tween 80
Aligation Method
Tween 80
15.0
7.7
12.0
Span 80
4.3
3.0
10.7
emulsifier 10%
= 10
emulsifier 10.7
emulsifier 7.7
Tween 80
= 10
=
7.7 x10
10.7
= 7.2
Span 80
= 10-7.2 = 2.8
1.
4 Dry gum method (Continential method), Wet gum method (English
method), Bottle method (Forbes bottle method) Auxiliary method 4
primary emulsion O:W:G
Type of oil
Fixed oil (cod liver oil, castor oil
,almond oil, arachis oil)
Mineral oil (liquid paraffin liquid
petrolatum
Linseed oil & volatile oil (turpentine
oil, methyl salicylate, cinnamon oil,
peppermint oil)
Oleoresin
09/06/11
Acacia
O:W:G
Tragacanth
O:W:G
4:2:1
40:20:1
4:2:1, 3:2:1, 2:2:1
40:20:1
3:2:1
2:2:1
30:20:1
20:20:1
1:2:1
10:20:1
Part II
Page 33 of 126
1.1 Dry gum method external phase internal phase gum

( o/w emulsion)
1. O:W:G oil gum
2.
5 primary emulsion film
cream cracking
sound
3. primary emulsion 2-3
4.
1.2 Wet gum method internal phase external phase gum
( o/w emulsion)
1. O:W:G
2. gum mucilage
3. oil mucilage
ropy
4. primary emulsion 2-3
5.
1.3 Bottle method oil volatile oil oil
1. Calibrate
2. O:W:G
3. gum
4. oil
5. primary emulsion
6.
1.4 Auxiliary method dry gum/wet gum method hand
homogenizer emulsifier
gum acacia emulsify gelatin, methyl cellulose
09/06/11
Part II
Page 34 of 126
2. emulsifier natural gum surfactant

emulsifier
2.1 Beaker method
- internal phase external phase
1. aqueous phase oil oil phase

2. o/w emulsion oil phase aqueous phase w/o emulsion
aqueous phase oil phase
fat, wax, surfactant solid semisolid water bath
oil phase heat aqueous phase (65-75 )
- external phase internal phase phase emulsion

- Beaker method beaker
beaker method
1. 2 phase
2. phase phase

3. Water phase
4. volatile oil, alcohol (temp. < 45 C)
oil
2.2 Nascent soap method In situ soap method
soap emulsifier
emulsifier monovalent soap o/w emulsion monovalent soap
sodium oleate (sodium +1) emulsifier divalent soap w/o emulsion
divalent soap 2 calcium oleate (calcium +2)
1. Flocculation (floccules)
2. Creaming (upward creaming)
09/06/11
Part II
Page 35 of 126
(downward creaming)
creaming reversible
creaming Stokes law
v = creaming (cm/sec)
d = (cm)
g = (980 cm/sec2)
1 = (g/ml)
2 = (g/ml)
= (poise g cm-1 sec-1)
3. Coalescence
2 (breaking)
breaking
1) surface free energy
- Globule surface free energy
2)
-
3)
- critical point internal phase
4) diffuse double layer

- Zeta potential
- electrolyte
09/06/11
Part II
Page 36 of 126
4. Oswald ripening
2 1 1

5. Phase inversion
- chemical reaction o/w sodium stearate calcium
chloride calcium stearate w/o
- electrolyte, alcohol hydrophilic emulsifier

Coalescence phase separation
stress test
1)
-
- freeze-thaw
cycle -5 C 40 C cracking

2)
- creaming ,
-
2 phase creaming centrifuge

09/06/11
Part II
Page 37 of 126
^^
1. emulsion
1. Flocculation and creaming
2. Coalescence and breaking
3. Flocculation and caking
4. Deterioration and microorganism
5. phase inversion
2. emulsion mineral oil acacia dry gum method
1. mineral oil acacia mucilage
2. acacia mineral oil
3. mineral oil acacia
5. mineral oil
3. benzoic acid o/w emulsion
A. Partition coefficient
B. Dissociation constant
C. Critical micelle concentration
1. A
2. B
3. C
4.A,B
5.A,B,C
4. Mineral oil emulsion emulsifier (Span 80 Tween 80)

40/60 HLB Span 80 = 4.3, Tween 80 = 15 HLB
10.7
5. zinc oxide, calamine 8 mg olive oil, Ca(OH)2 100

ml
1. Wet gum method
2. Dry gum method
3. In situ soap method
4. Bottle method
5. Suspension method
6. Pharmagel A
1. Auxilliary method
2.
09/06/11
Part II
Page 38 of 126
3. methylcellulose
4. Pharmagel A heat 100 20
5. Homoginizer
7. phase reversion
1. emulsifying agent
2.
3. phase volume ratio
4. internal phase external phase
5. external phase internal phase
8. mineral oil 0.2%, rose oil, water rose oil, borax,
glycerine, cetyl alcohol
1. emulsifying agent phase oil
2. emulsifying agent phase
3. rose oil water rose oil
4. borax phase
5. borax phase oil
9. dry gum method primary emulsion
1. 2.
3. crakling sound
10. creaming o/w emulsion

1. downward creaming
2. Film emulsifying agent oil
3. oil
4. irreversible process
5. oil cream
11. o/w very water soluble
incoperation
12. Dry gum method

gum oil
09/06/11
Part II
Page 39 of 126
2.5 Semisolid dosage form

(Ointments, Creams, Pastes, Jellies)
Ointments ()
(semi-solid preparations)
(0intment base)
Ophthalmic ointment eye ointment
2
1. (active ingredients)
2. (ointment bases) (emollient)
(protective) 2
1) (skin penetrating ability)
3
1.1 epidermatic ointment
(keratosis)
1.2 endodermatic ointment

1.3 diadermatic ointment

2) 4
2.1 (oleageneous or hydrocarbon ointment base)

Hydrocarbons mineral oil, petrolatum, paraffin, petrolatum substitute
olive oil, cotton seed oil
beeswax, spermaceti dimethicone

2.2 (absorption ointment base)

wool fat(
09/06/11
Part II
Page 40 of 126
25-30% lanolin), wool alcohol, cetyl alcohol, stearyl

alcohol
2.3 Emulsion ointment base 2
2.3.1 W/O Emulsion ointment

2.3.2 W/O Emulsion ointment base base

emulsifier 3
a) Anionic emulsifier alkyl sulfonate, alkali soaps,metallic soaps
alkali soaps
alkali soaps
b) Cationic emulsifier cetrimide

c) Non-ionic emulsifier
hydrophilic lipophilic
2.4 (Water soluble ointment base)

polyethylene glycol:PEG bentonite or veegum
2
1. (fusion)
hard paraffin

2. (incorporation or mechanical incorporation)

1.
( levigating agent)
smooth paste geometric dilution
09/06/11
Part II
Page 41 of 126
levigating agent
- Light mineral oil vegetable oil
w/o
- Glycerin w/o
(melted base) levigeting
agent
1.
(
cetyl alcohol 4-5%)
2.
(bleeding)

Creams
(thick liquid
emulsion) oily cream aqueous cream

2
1. (W/O cream hydrophobic creams)

cold cream
2. (O/W cream hydrophilic creams)

vanishing cream
1.
09/06/11
Part II
Page 42 of 126
2.
2.1 Petrolatum, glycerol, urea
2.2 (Thickeners) beeswax, paraffin, candililla wax
2.3

HLB 4-6
HLB 8-18
HLB
sorbitan monostearate tween 80
Rx
Liquid paraffin
35
Wool fat
Cetyl alcohol
10
Emulsifier
Purified water to
100
M.ft. cream (o/w)

1. required HLB
35+1+10 = 46%
required HLB Liquid paraffin = 35x12/46
= 9.13
required HLB Wool fat
= 0.22
= 1x10/46
required HLB cetyl alcohol = 10x13/46

required HLB
= 2.83
= 9.13+0.22+2.83
= 12.18
2 sorbitan monostearate tween 80

HLB 4.3 15
Tween 80
15
7.88
12.18
sorbitan monostearate
4.3
2.82
10.7
10.7 Tween 80 = 7.88

7 Tween 80 = 7x7.88/10.7 = 5.16
09/06/11
Part II
10.7 sodium monostearate

7
sodium monostearate
Page 43 of 126
= 2.82
= 7x2.8/10.7
= 1.84
sorbitan monostearate 1.84 Tween 80 5.16

2.4
2.5
2.6
2.7
1.
70-75
2.

3.

4.
40

5. homogenizer, colloid mill roller mill

30-40

09/06/11
Part II
Page 44 of 126
Pastes
Pastes

50%

2
1. (Fatty pastes)

petrolatum, mineral oil, bees wax, wool fat etc.
2. (Nongreasy pastes)
glycerin
gelatin pectin tragacanth

1.

Geometric dilution
2.
pectin tragacanth
hydrate glycerin

09/06/11
Part II
Page 45 of 126
(bleeding)

Jellies and gels
Gels
(dispersed phase) inorganic
particles (dispersion medium)

organic molecules
Jellies
1. (dispersed phase)
Aluminium hydroxide
2. (dispersion medium)
3. (Pharmaceutical Necessities)
4.
4.1
- agar 0.5%w/v
alcohol
- acacia 2 alcohol
particle agglomeration tragacanth preservative
- gelatin 2-15% 5-10 2 type Type A
pH 3-4.5 Type B pH 5-7

- pectin pH Ca+
09/06/11
Part II
Page 46 of 126
preservative
- tragacanth alcohol
( glycerin, alcohol )
4.2
- Methylcellulose (MC)
pH (3-11)
- Hydroxypropylcellulose (HPC)

- Hydroxymethycellulose (HMPC) alcohol
- Sodium carboxymethylcellulose (SCMC) MC HPMC

4.3
- Carbomer

KOH, NaOH
Poloxamer thermoreversible gel

Poloxamer Poloxamer
1. Temperature effect
2. floccules
3. Aluminiumhydroxide gel silica gel

sodium siligate

(set-up) (syneresis)

09/06/11
Part II
Page 47 of 126
semisolid dosage form

Ointment
(0intment base)
09/06/11
Creams

emulsion
ointment
Pastes
(0intment base)
(
50%)
Jellies & Gels
(colloid)
Part II
Page 48 of 126
1.
Suppositories
2

, ,

- /
- //
- First pass effect

-
(theophylline, sulbutamol),
(diazepam), (chlorpheniramine),
(paracetamol), (chlorpromazine)
2. (
)
2.1 (Oleaginous suppository base, fatty
suppository base, lipophilic suppository base)
Theobroma oil (Cocoa butter)
30-36C 30C
-
-
-
-
09/06/11
Suppositories () (solid
dosage form)
rectal suppositories
vaginal suppositories, Pessaries

urethral suppositories, Bougies
1
(suppository base)

-
-
- (3 )
-
-
-

polymorphism -Crystal m.p. 18C, -Crystal m.p.
22C, -Crystal m.p. 28C, -Crystal m.p. 28C -Crystal
m.p. 28C
-
-
-
-
-
-
-
Part II
Stearic-Oleic Acid Suppository Bases

- Fatty substitute suppository base
- stearic acid + Oleic acid

- acetyl 17% + almond oil 83%
stearic
acid ( ), oleic acid (
) oleaginous materials
Othersyntheticoleaginoussuppositorybases
Fractionalpalmkerneloil
Suppocire
IVNovata
Wecobee
MassaEstarinum
Fattibase
Page 49 of 126
Dehydag bases
theobroma oil
Dehydag base,Dehydag ,Dehydag baseG

polymorphs

Witepsols
theobroma oil
4series:H,W,S,E
Witepsol H

Witepsol W
+
+
Witepsol S
Witepsol Em.p. m.p.
2.2 (Water soluble suppository base,

water miscible suppository base)
Glycerinated gelatin (Glycero-gelatin)

-
- glycerin, gelatin,
USP
BP
Glycerin
70%
70%
Gelatin
20%
14%
10%
16%
, laxative effect,
, , incompatibility
Polyethylene glycol (PEG)

- Polyethylene glycol 2

- PEG.. ( )
PEG 1000
MW 950 1050
PEG 200-600
liquid like wax like
- Macrogol, Carbowax, Polyglyol
09/06/11
-
-
-
-
-
- tannin, salicylic acid PEG
- PEG PEG
- (plasticizer)
Part II
2.3 (Miscellaneous suppository base,

hydrophilic suppository bases, water dispersible suppository
bases)

Glycerin Suppositories USP (Soap Suppositories)
= Glycerin+Sodium Stearate+Purified Water
Glycerin Suppositories USP
glycerin
sodium
Stearate
glycerin
3.

,
, Antioxidants, Preservatives
1. (Hand rolling and shaping or cold hand shaping)

2. (Compression or Cold Compression)
3. (Fusion or Molding from melt)
: 10%
2
4. Displacement value
Displacement value =
1
displacement value aspirin theobroma oil = 1.3
aspirin 1.3 g
theobroma oil 1 g
09/06/11
Page 50 of 126

Tween 6191%+Glyceryl monostearate 10%
Tween 6191%+Glyceryl monostearate 10%+
Spermaceti10%
Witepsol W3580%+Tween 2010%+Tween
6110%
Witepsol E7570%+SCMS1%+Tween 204%
+water25%
(FusionorMoldingfrommelt)
1.
2.
3. meltedbase
mold
( lubricate )
(Theobroma oil,Glycerogelatin,
PEG / )
4. mold
5.
displacementvalue
1. base 1
1.75 g/
2.
A 0.3 g 1
1.864 g/
3. base 1
= 1.864 0.3 = 1.564 g
4. base
= 1.75 1.564 = 0.186 g
5. displacement value A base = 0.3/0.186 = 1.6
Part II
displacement value
20
Bismuth Subgallate
0.3 g
Theobroma oil
q.s.
displacement value bismuth subgallate = 3,
1 (blank weight) = 2 g

Bismuth Subgallate 3 g
1g
Bismuth Subgallate 0.3 20 g (10.320)/3 = 2 g
Theobroma oil 1
2g
Theobroma oil 20
220 = 40 g
Theobroma oil 40 2 = 38 g
2 1
1 . 1
= 2.3 g
1
= 0.4 g
. 1 = 2.3 0.4 = 1.9 g
. 5 = 1.9 5
= 9.5 g
white wax 0.19 g + oleic acid 4.655 +
stearic acid 4.655 g
water bath 2 g
mold 5
+ 3
Page 51 of 126
displacement value

Paracetamol Suppositories
Each suppository contains:
Paracetamol
0.4 g
Fatty Substitute Suppository Base
q.s
M.ft Suppos. Mitte#3
Fatty Substitute Suppository Base white wax 2%, oleic acid 49%, stearic acid aa
49%
1 1
1. 30 g
white wax 0.6 g + oleic acid 14.7 + stearic acid 14.7 g
water bath
2.
1.6 g melted base

3. 4 melted base 1 4
4.
2.3 g
5.
5.1

5.2 (Uniformity of weight) 20

5 % 2 20
5 % 10 %
5.3 (Uniformity of content) 10
1 85-115 %
75-125 %
2-3 85-115 %
75-125 % 20
3 30 85-115%
75-125 %
5.4
5.5
5.6
5.7
5.8
5.9(Dissolutionstudy)
5.10(Invivostudy)
5.11(Stabilitystudy)
09/06/11
Part II
Page 52 of 126
2.6 Suppositories
1.
Suppositories () (solid dosage form)

rectal suppositories
vaginal suppositories, Pessaries
urethral suppositories, Bougies

1 (suppository
base)
2
1.
, ,
2.
- /
- //
- First pass effect
-
(theophylline, sulbutamol), (diazepam),
(chlorpheniramine), (paracetamol),
(chlorpromazine)

(3 )

09/06/11
Part II
Page 53 of 126
3
1.
2.
3.
2. ()
2.1 (Oleaginous suppository base, fatty suppository base, lipophilic
suppository base)
Theobroma oil (Cocoa butter)
30-36C 30C
-
-
-
-
- polymorphism -Crystal m.p. 18C, -Crystal m.p. 22C, Crystal m.p. 28C, -Crystal m.p. 28C -Crystal m.p. 28C
- Theobroma oil
-
(stiffening agent) beeswax, spermaceti
- chloral hydrate, volatile oils
beeswax, spermaceti
-
- polysorbates, cholesterol,
wool fat, emulsifying wax theobroma oil
09/06/11
Part II
Page 54 of 126
Stearic-Oleic Acid Suppository Bases

- Fatty substitute suppository base
- stearic acid + Oleic acid
- acetyl 17% + almond oil 83%
stearic acid (
), oleic acid () oleaginous materials
Dehydag bases
- theobroma oil
- Dehydag base , Dehydag , Dehydag base G
- polymorphs
-
Witepsols
- theobroma oil
- 4 series : H, W, S, E
- Witepsol H

Witepsol W
+
Witepsol S
+
Witepsol E
m.p. m.p.
Other synthetic oleaginous suppository bases
- Fractional palm kernel oil - Suppocire
- IV Novata
- Wecobee
- Massa Estarinum
- Fattibase
2.2 (Water soluble suppository base, water miscible
suppository base)
09/06/11
Part II
Page 55 of 126
Glycerinated gelatin (Glycero-gelatin)

-
- glycerin, gelatin,
Glycerin
Gelatin
USP
70%
20%
10%
BP
70%
14%
16%
, laxative effect, ,
, incompatibility
Polyethylene glycol (PEG)
- Polyethylene glycol 2

- PEG.. ( )
PEG 1000
MW 950 1050
PEG 200-600
liquid like wax like
- Macrogol, Carbowax, Polyglyol
-
-
-
-
-
-
-
- tannin, salicylic acid PEG
PEG PEG
- (plasticizer)
09/06/11
Part II
Page 56 of 126
2.3 (Miscellaneous suppository base, hydrophilic suppository bases, water

dispersible suppository bases)
Glycerin Suppositories USP (Soap Suppositories)

= Glycerin+Sodium Stearate+Purified Water
Glycerin Suppositories USP
glycerin
sodium Stearate
glycerin

- Tween 61 91% + Glyceryl monostearate 10%
- Tween 61 91% + Glyceryl monostearate 10% + Spermaceti 10%
- Witepsol W 35 80% + Tween 20 10% + Tween 61 10%
- Witepsol E 75 70% + SCMS 1% + Tween 20 4% + water 25%
3.

, , Antioxidants, Preservatives

1. (Hand rolling and shaping or cold hand shaping)
2. (Compression or Cold Compression)
3. (Fusion or Molding from melt)
: 10%
2
(Fusion or Molding from melt)
1.
2.
3. melted base mold ( lubricate )
(Theobroma oil, Glycero-gelatin
, PEG
/)
09/06/11
Part II
Page 57 of 126
4. mold
5.
4. Displacement value
Displacement value =
1
displacement value aspirin theobroma oil = 1.3
aspirin 1.3 g theobroma oil 1 g
displacement value
1. base 1
1.75 g/
2.
A 0.3 g 1
1.864 g/
3. base 1 = 1.864 0.3 = 1.564 g
4. base = 1.75 1.564 = 0.186 g
5. displacement value A base = 0.3/0.186 = 1.6
displacement value
20
Bismuth Subgallate 0.3 g
Theobroma oil
q.s.
displacement value bismuth subgallate = 3, 1 (blank weight) = 2
g
Bismuth Subgallate 3 g
1g
Bismuth Subgallate 0.3 20 g (10.320)/3 = 2 g
Theobroma oil 1
2g
Theobroma oil 20
220 = 40 g
Theobroma oil 40 2 = 38 g
displacement value

09/06/11
Part II
Page 58 of 126
Paracetamol Suppositories
Each suppository contains:
Paracetamol
0.4 g
Fatty Substitute Suppository Base q.s
M.ft Suppos. Mitte#3
Fatty Substitute Suppository Base white wax 2%, oleic acid 49%, stearic acid aa
49%
1 1
1. 30 g
water bath
2. 1.6 g melted base
3. 4 melted base 1 4
4.
2.3 g
2 1
1 . 1
= 2.3 g
1
= 0.4 g
. 1
= 2.3 0.4 = 1.9 g
. 5
= 1.9 5
= 9.5 g
water
bath
2 g
mold 5
+ 3
5.
5.1

5.2 (Uniformity of weight) 20
5 % 2 20 5 %
10 %
5.3 (Uniformity of content) 10
1 85-115 %
75-125 % 2-3
09/06/11
Part II
Page 59 of 126
85-115 % 75-125 % 20
3 30 85-115%
75-125 %
5.4
5.5
5.6
5.7
5.8
5.9(Dissolution study)
5.10(In vivo study)
5.11(Stability study)
09/06/11
Part II
Page 60 of 126
2.7 (Tablet excipients)
1. (active ingredients)
2. (diluents or fillers)
3. (binders)
4. (disintegrant)
5. (lubricants)
6. (colours) (Flavours) (sweeteners) (adsorbents)
(surfactants)
1. (Diluents or Fillers)

)
)
)
)
2 lactose,
sucrose, manitol, sorbitol dextrose starch, calcium sulfate, calcium
carbonate, dibasic calcium phosphate, tribasic calcium phosphate cellulose
2
- (Wet granulation diluent)
- (direct compression diluent)
1.1
Lactose
15% sucrose
whey of cows milk
crystalline amorphous lactose
-lactose -lactose 60100 mesh
microcrystalline cellulose, starch lubricant lactose
09/06/11
Part II
Page 61 of 126
3% adsorbed water 0.1% 75% 103-105

o
C 120 oC 80 oC adsorbed water
- Mailard type condensation

primary amino group
base catalyzed alkaline lubricant (browning
reaction) amorphous form cystalalline
form
Sucrose

1 % granular, fine, superfine confectioner sugar
3% corn starch

1)
2) (hygroscopic)
3) overwet
4) ( incompatability)
ascorbic acid
5) sulfite
6) glucose fructose ( invert sugar )
7) reducing sugar alkaline
Starch

12-14
(moisture content)

Dibasic calcium phosphate
09/06/11
Part II
Page 62 of 126
2 dibasic calcium phosphate

anhydrous dibasic calcium phosphate dehydrate ( 100 o C)
calcium chloride sodium phosphate
(0.3 1 )
tapped density
Calcium sulfate

calcium carbonate sulfuric acid
2 anhydrous dehydrate
80 o C dehydrate
1) calcium ion amines, amino acid,

peptides
2)
3) Polymer
Calcium carbonate
ethanol , alum
ammonium salts cohesive

1.2 (Direct Compression Diluent)

( Compressibility ) ( Flowability ) (
Carrying capacity Dilution potential )
( Compressibility )

Avicel
Compressibility profile starch
09/06/11
Part II
Page 63 of 126
( Flowability )

scanning electron
microscopy (SEM)
( Carrying capacity Dilution potential )
Dilution potential

1)
2)
3)
4)
5)
6) (reworkability)
Lactose
anhydrous
compressibility lactose spray-dried
lactose
compressibility
Sucrose
Di-Pac
sucrose 97 %, dextrin 3 %
Dextrose
sucrose
Mannital & Sorbital
sorbital
D-sorbital lactose amine
Starch
09/06/11
Part II
Page 64 of 126

- Starch 1500 : pregelatinised starch partial hydrolyzation
3 120 oC

magnesium stearate stearic acid
- Spray dried rice starch : spray drying
flowability compressibility
Cellulose

cellulose
- Microcrystalline cellulose :
compressibility
alkaline stearate 0.75 %
80 %
20 % 10-25 % Avicel
PH 101, 102 (102 )
- Inorganic Calcium Salt :
1. calcium hydrogen phosphate-dihydrate : compressibility
Emcompress, DiTab
2. Tricalcium phosphate : compressibility 1
vitamin E, A Tritab
2. (Binder)
cohesive
1.
2.
3.
4.
macromolecule
Gelatin
( 1-4 %
)
09/06/11
Part II
Page 65 of 126
Starch

Tragacanth
mucilage
Acacia

polymer
Polyvinylpyrrolidone (PVP)

Polyvinylacetate (PVAC)

macromolecule
Hydroxyethylcellulose (HEC)

Hydroxypropyl methylcellulose (HPMC)
Organic solvent
Carboxymethylcellulose (CMC)

3. (Disintegrant)

Starch
Corn starch
Sodium starch glycolate (Explotab, Primogel)

(superdisintegrant)

Cellulose (Microcrystalline cellulose:Avicel, Cross-link sodium carboxymethylcellulose:Ac-Di-Sol)
superdisintegrant
Alginate
09/06/11
Part II
Page 66 of 126

Pregelatinized starch (starch 1500)

Gums (agar, tragacanth)
Cross-link PVP (polyplasdone XL)

4. (lubricants)

punch die
1. (glidant) Colloidal silicon dioxide (Aerosil), Talcum, Corn starch
hopper
-
- van der waals
-
2. (lubricant)

die
capping

- Metal soap (Magnesium stearate) :
stearic acid
- Stearic acid :
- Hydrogenated vegetable oil (Sterotex, Lubritab) :
alkaline stearate
3. (antiadherent)
punch die
(lubricant) (glidant)
09/06/11
Part II
Page 67 of 126
1. Compressed tablets (CT)

2. Multiple compressed tablets (MCT)
3. Sugar-coated tablets (SCT)
4. Film-coated tablets (FCT)
5. Gelatin-coated tablets
6.
7.
8.
9.
Enteric-coated tablets (ECT)

Buccal or oral sublingual tablets
Chewable tablets
Effervescent tablets
10. Molded tablets (MT)

11. Tablet triturates (TT)
12. Hypodermic tablets (HT)
13. Dispensing tablets (DT)
14. Immediate release tablets (IR)
15. Instant disintegrating/dissolving tablets
16. Extended release tablets (ER)
( compressed tablet manufacture )
1.granulation
1.1 wet granulation :
1.2 dry granulation :
2.direct compression
2.1 powder : flowability compressibility
2.2 crystal : (crystal form) flowability
1. Flowability
2. Compressibility
wet granulation
-
09/06/11
Part II
Page 68 of 126
1.
2. compressibility density
3.
:
1. active ingredient, diluent/filler (disintegrant)

2. damp mass binder
3. pellets granules (wet screening 6-20 mesh) granules
4. granules
5. (dry screening) lubricant (disintegrant)
punches dies
6.
active ingredient, diluent/filler, disintegrant filler lactose (),

microcrystalline cellulose (), starch (), powdered
sucrose, calcium phosphate ( )

Calcium salt tetracycline
Lactose primary, secondary amine
microcrystalline cellulose compactability, compatibility
disintegrant
Starches 5-10%, 20%
Carboxymethyl starch sodium (CMS-Na) ; primojel, explotab
Sodium starch glycolat 5-300%
Microcrystalline cellulose 10%
Croscarmellose sodium (CCNa); Ac Di Sol 2%
Low-substituted hydroxypropyl cellulose (L-HPC)
Crospovidone(CPVP); Polyplasdone 2%
disintegrant 3
Internal : disintegrant granule ()
External : disintegrant granule
internal-external :
09/06/11
Part II
Page 69 of 126
damp mass
1. binder powder mixture
2. binding agent povidone, corn starch 10-20%,
glucose 25-50%, methylcellulose 3%, Carboxymethyl cellulose Microcrystalline
cellulose
3. binding agent
lubricant
1. lubricants
2. Lubricants flow granule, friction ,
3. Lubricants magnesium stearate, calcium stearate, fumed silicon dioxide, stearic
acid, talc, sodium stearyl fumarate ( 0.1-5%)
Compress tablet All-in-one glanulator methods
fluid-bed granulator microwave vacuum processing method
dry granulation
:
:
2
- Slugging
1.
2. Slugging compressing
3.
4.
5. disintegrant /lubricant
- Roller compaction
1. ( binding agents MC HMC 6-12% )
2.
Direct Compression
: cohesive KCl
09/06/11
Part II
Page 70 of 126
excipient filler, disintegrants, lubricants, glidants Direct
Compression
1. Single-punch presses
Filling compression ejection
2. Multi-station rotary presses

over fill
09/06/11
Part II
Page 71 of 126
Tablet formulation and design

2
1. Research and development :

preformulation
2. Trial and error (cooking) :

Preformulation studies, Systemic approach

to
Tablet design
A. Preformulation studies

phyhsicochemical
Profile
Preformulation data
1. Stability (solid state) :
2. Stability (solution state) : excipient-drug stability
3. Physicochemical properties : pH profiles (,solvent )
09/06/11
Part II

4.
5.
Page 72 of 126
Physicomechanical properties: particle size, bulk and tab density, crystal form,
compressibility, photomicrograph, ,,,,
In vitro dissolution : pure drug, effect of excipient and surfactant
Preformulation data X
-
- Compressibility
- polymorphism wet granulation, Direct compression
- pH=7.5 wet method, surfactant, complex
- pKa = 3.1
B. Systemic approach to Tablet design

1.
-
-
2.
- Granulation : , low compressibility, low bulk density
- Drug stability : non-aqueous wet granulation, dry method
- Solubility : wet granulation hydrophobic drug

- Density :

- :
3. : compressible properties, bioavailibility

4. :
-
-
-
-
(Experimental design) factorial design,
optimization
5. :
09/06/11
Part II
Page 73 of 126
6. : bioequivalent
7. (scale up)
A. Binding

(straitation)
- lubricant lubricant
- lubricant 30
-
-
- tapered die
B. Sticking, Picking and filming
Sticking
Picking Sticking
Filming Picking
1. ,
2. antiadherent
3. adsorbent silicon dioxide, aluminium hydroxyl, microcrystalline cellulose
4. ,
09/06/11
Part II
Page 74 of 126
5.
C. Capping and laminating
Capping
1.
2.
3.
4. Elastic recovery stress relaxation
Laminating
1.
2. elastic
recovery
3.
4. precompression
5.
6.
7. adsorbant hygroscopic sorbital
8. tapered die
D. Chipping and Cracking
Chipping
lower punch die

Cracking
capping binding sticking

E. Drug and dye migration

content uniformity potent drug , motting
1. tray dryer fluid-bed dryer

2. tray dryer
3. granulation fluid
09/06/11
Part II
Page 75 of 126
4. 40-80
5. lake dye
6.
1
2
3
1. Compressibility property

Content
Uniformity Weight Variation
2. Bioavailability property
Disintegration time
Dissolution time
3. Stability property
2
1. Research and Development (R&D)
(Preformulation) pilot
scale Validation
2. Trail & Error (Cooking)

1. Preformulation Studies

Physicochemical profile
1. Stability (Solid state)
09/06/11
Part II
Page 76 of 126
2. stability (Solution) excipient-drug stability

3. Physicochemical property solubility pH profile of solution/dispersion
4. Physicomechanical property particle size, bulk and tap density, crystal form,
compressibility, melting point, color
5. In vitro dissolution pure drug,
Preformulation data
X pyridine
polymorph
pH 7.5 pKa = 3.1
X

2. Systemic approach to tablet product design

1.

2.
(dose)

Wet granulation

3.

4.

09/06/11
Part II
Page 77 of 126
5.

6.
7.
3. Tablet excipient

1.

2.

3.
4.

Consolidation NaCl

1.
Tetracycline
2.
dicalsium phosphate, lactose
sorbitol, sucrose
3.

09/06/11
Part II
Page 78 of 126
1. starch,
methylcellulose sodium carboxymethylcellulose magnesium, calcium,
aluminium
2. acacia

3.
Glucose > acacia > gelatin > simple syrup > starch

4.
5. 2

1. (Superdisintegrant)
explotab, ac-di-sol
2. Superdisintegrant
3.
4. extragranular disintrgrant

1.

2.
1
Active ingredient
(Cimetidine)
09/06/11
Master formular
200 mg
1
200 mg
500 tablets
100 g
Part II
Diluent (Lactose)
Disintegrnt (Corn starch)
Binder 10%w/w (Starch
paste)
Lubricant (Mg stearate)

100 mg
10 %
qs
5% of dried granule
Total
100 mg
30 mg
4 mg
Page 79 of 126
50 g
15 g
2g
16 mg
350 mg
8g
175 g
Cimetidine 500 200 mg/

10 % w/w starch paste 30 20 g
Starch paste 2 g
1
500
100 g
50 g
(100 + 50)10/100 = 15 g
2

7.5 g
20 g
2g
100 + 50 + 7.5 + 2 = 159.5 g

5% 159.5(5/100) = 8 g
500 + +
159.5 + 8 + 7.5 = 175 g

1
175/500 = 350 mg
1
100 g
50 g
(100 + 50)10/100 = 15 g
2

7.5 g
20 g
2g
100 + 50 + 7.5 + 2 = 159.5 g

09/06/11
Part II
Page 80 of 126
140 g
5%
140 * (5/100) = 7 g
500 + +
159.5 g
7.5 g
140 g
140 (7.5/159.5) = 6.6 g
140 + 7 + 6.6 = 153.6 g

1
159.5 g
500
140 g
500(140/159.5) = 438.9 = 438
153.6 g /438
= 350.7 mg/

1.
2. Punch, die
3.
4.

2 Teclock micrometer
caliper
2
Teclock dial thickness tester

09/06/11
Part II
Page 81 of 126
(Rule of thumb)

(axial)
(radial)

Stoke-Monsanto hardness tester
1.
2. 0 0
3.

4. kg
4 kg 4 8 kg
Stoke Monsanto hardness tester

1.
2.
3.
4.
09/06/11
Part II
Page 82 of 126
Roche friabilator 12
1 100 /4
USP 30
1. 650 mg 6.5 g
2. 650 mg 10
3.
4. Roche friabilator 100 4
5.
6. % Friability
% Friability = W0 W 100
W0

2
3 1 %
% Friability
% Friability Theophylline 6.5 g
6.35 g 2 2
% Friability
Before (W0)
After (W)
1
6.500
6.435
1
2
6.500
6.447
3
6.500
6.438
W0 W 100
W0
2 % Friability 3
1.0%
Before (W0)
After (W)
09/06/11
% Friability
Part II
1
2
3
% Friability
Page 83 of 126
6.500
6.435
6.500
6.447
6.500
6.438
= (6.435 + 6.447 + 6.438) / 3 = 6.44
= (6.5 6.44)*100/6.5 = 0.923 % 1%
Dissolution test
, Bioavailability

Dissolution test Disintegrating time
1. Dissolution Apparatus Dissolution test Apparatus
Apparatus 1 Basket
1. Vessel : hemispherical bottom 1,2,3 monograph
2. Water bath vessel vessel 37 0.5 C
3. Stirring element Basket shaft
4. Motor Shaft Monograph
Apparatus 2 Paddle Apparatus 1 Basket

vessel
09/06/11
Part II
Page 84 of 126
Reference standard tablet

Certificate prednisolone tablet RS, USP salicylic acid tablet RS

1. monograph
2. buffer pH 0.5 unit
3.
1. Dissolution medium 37 0.5 C

2. apparatus 1 basket apparatus 2 vessel
3. shaft
4.
5. medium
6.
7.
8.
1.
2.
2%
procedure procedure for a pooled sample
1.
2. 6 12
3.
Dissolution test (USP 30)
Pooled sample
1. Monograph
acceptable table
2. S1 S2 S3
09/06/11
Part II
Stage
S1
S2
Number
tested
6
6
S3
12
Page 85 of 126
Unit Sample
Acceptance Criteria
6 Q + 5%
12 ( S1 + S2) 12 Q
Q 15%
24 ( S1 + S2 + S3) 24
Q 2 Q -15%
Q 25%
Pooled sample
1. monograph acceptable
value for pooled sample
2. S1 S2 S3
Acceptable table for pooled sample
Stage
Number
Acceptance criteria
tested
S1
6
Q + 10%
S2
6
( S1 + S2)
Q + 5%
S3
12
( S1 + S2+ S 3 )
Q
Dissolution test
Theophylline USP 30 NF25 200
mg/tablet
Theophylline tablet contain not less than 94.5 % and not more than 106.0 % of the label
amount of anhydrous theophylline C7H8N4O2
Dissolution
Medium : water 900 ml
Apparatus 2 : 50 rpm
Procedure :
Tolerance : Not less than 80% Q of the label amount of anhydrous theophylline C7H8N4O2 is
dissolve in 45 minites
09/06/11
Part II
( mg )
1
2
3
4
5
S1
190
192
159
193
190
S2
192
189
194
192
152
S3
190
189
190
197
196
192
190
198
189
196
% 200 mg
% Dissolution
1
2
3
4
5
S1
95
96
79.5
96.5
95
S2
96
94.5
97
96
76
S3
95
94.5
95
98.5
98
96
95
99
94.5
98
Page 86 of 126
6
191
190
192
192
6
95.5
95
96
96
USP 30 Unit sample

Stage
Number
Acceptance Criteria
tested
S1
6
6 Q + 5%
S2
6
12 ( S1 + S2) 12 Q
Q 15%
S3
12
24 ( S1 + S2 + S3) 24
Q 2 Q -15%
Q 25%
Q = 80 %
S1 Q + 5% = 80 + 5 = 85% 3 79.5%
S1 S2
S2 12 (S1 + S2) = 92.7 % Q (80%) Q
-15% = 80 15 = 65% 12 Q- 15 %
09/06/11
Part II
Page 87 of 126
1. ,
2.
3.
4. imcopatability dosage form
5.
1.
- ,
-
- Convexity , subcoating
-
2.

- Pan-ladling: ladle
film-coating
- Pan-spray method : spray equipment
3.
Coating process =
4.
4.1 Conventional Coating System
Coating Pan
- Circular or doughnut shaped
- , 25-40o
Warmed-air and exhaust System
- Inlet air
T= 50o C, R.H.= 35 %
- Exhaust air
Solvent
Spray system
a. Airless atomization (hydraulic spray system)
09/06/11
Part II
Page 88 of 126
- coating solution droplet orifice

- droplet size
orifice air pressure
- 1) small scale 2) clogging
b. Air atomization ( Pneumatic spray system)
- coating solution orifice (peristaltic pump)
- small scale
- 1) 2) droplet
(Polishing pan)
4.2 Perforated Pan
(perforated)
exhaust plenumm()
3 - Accela-cota
- Hi-coater
- Dria-coater
4.3 Fluidized bed system
Fluidization pellet
Spraying of coating solution
Drying by fluidized air
- Top Spray Coater

- Bottom Spray Coater
- Rotor-tangential Spray Coater
1. (Sugar Coating) 5
1) Protective coating (Sealing) 5 % core tablet
shellac, zein (), cellulose acetate phthalate, polyvinyl
acetate phthalate
2) Subcoating 45 % ,
sealing sugar coat talcum , acacia
3) Smooth Coating 35 % ,
Glossing Syrup
09/06/11
Part II
Page 89 of 126
4) Colour coating and finishing (Syrup Coating) 15 % syrup

2
5) Polishing Coat wax carnuba wax,
white bee wax
2. (Film Coating)
, ,
, vehicle 2
1) Oraganic solvent-based film coating: Oraganic solvent vehicle
2) Aqueous film coating: vehicle
Material in Film Coating
- 2
1. Non-enteric HPMC, EC, HPC, PVP, PEG, Eudragit (grade: E, RL, RS)
2. enteric CAP, HPMCP, HPMCAS, PVAP, Eudagit ( grade: L,S)
-Solvent polymer polymer
, ethanol,
methanol, isopropanol, acetone
-Plasticizer : Tg (glass transition
temperature ) polymer polymer water soluble (PG, PEG
, glycerin), Oil soluble (castor oil, sorbitan ester)
-colourant
-Opaquant Tionium dioxide, Talcum, Magnesium
carbonate, aluminium hydroxide
, surfactant, antioxidant
09/06/11
Part II
Page 90 of 126
2.8 Modified release dosage form

controlled release
-
-
-
-
-
Type of controlled-release system:
- Polymer systems (diffusion control, chemical control, solvent control, physical
control;temperature)
Diffusion controlled system
-Reservoir system core polymer film
-Matrix system
Chemically controlled system
- the rate of polymer degradation, the rate of physical
erosion of polymer, the rate at which a drug is cleaved from the polymer backbone
1.Matrix system based on degradable polymers polymer
2.Pendant chain system polymer
Solvent controlled system
-Polymer swelling
pH sensitive polymer
Hydrogels :
Physically controlled system
-Magnetic fields
-Temperature gradient :
-pH
-Ionic strength
-Ultrasound : Ultrasound
-Pump systems (osmotic control)
-Osmotic pressure : semipermeable
osmotic
09/06/11
Part II
Page 91 of 126
sustained release
A (dose dumping)
B osmotic pump
C
1. A
2. B
3.C
4.A,C
5. B,C
5
09/06/11
Part II
Page 92 of 126
Powdersandgranules
Powders and granules

&
Capsules
powder granule
Powder
( + )
Granule powder particles
form particle
( + + )
Active ingredient antacid, laxative

Diluents lactose, kaolin, talcum
Other flavoring agent, coloring agent
Effervescent salts 2
1. Fusion method ():
1. Bulk powder or granules for internal use()

non-toxic
insufflation (snuff = ) dentrifices
( ) douche powders ( )
All ingredient sieve No.60 heat 93-104C

sieve No.4-10 dry 54C
2. Wet method ():
All ingredient + alcohol + sieve pack
2. Divided powder or granules (oral) for internal use

()
Effervescent salts sodium bicarbonate,
citric acid, tartaric acid
carbondioxide
3. Dusting powders for external use

- medicated dusting powder
Tolnaftate dusting powder PC
- sterile dusting powder
Chlorhexidine dusting powder BP
1. Comminution ( )
Trituration :
Pulverization by intervention :
Levigation : semisolid slab

spatula
2. Separation of particle size
3. Mixing
Spatulation : spatula
Tritulation :
Sieving :
09/06/11
!!!!
calculation of sodium bicarbonate used in the effervescent

formulation
Rx
Dibasic sodium phosphate, dry powder
200 g
Tartaric acid, dry powder
252 g
Citric acid, monohydrate
162 g
Sodium bicarbonate
qs.
Citric acid
H3C6H5O7.H2O + 3NaHCO3 Na3C6H5O7 + 4H2O + 3CO2
Tartaric acid
H2C4H4O6 + 2NaHCO3 Na2C4H4O6 + 2H2O + 2CO2
MW. Citric acid = 210.13 tartaric acid = 150.09 NaHCO3 = 84.01
Part II
Capsules
(Capsule)
unit dose
diluent
(Gelatin)
Gelatin partial hydrolysis collagen

gelatin 2
1.Gelatin type A acid hydrolysis
2.Gelatin type B basic hydrolysis
1. Hard gelatin capsule body ( ) cap ( )

2. Soft gelatin capsule gelatin shell 1
2.
000 5 0 5
65-1000 mg
3.
13-16% 10
***** 30-45% ******

Mg stearate 1%
hydrophobic bioavailability sodium lauryl
sulfate 1% bioavailability
09/06/11

-
-
-
-

-
-
-
Hard gelatin capsules
Capsule
Capsule
Page 93 of 126
1.
Diluent : plug-forming 2
-soluble diluent (lactose) : hydrophobic drug
-Insoluble diluent(starch,MCC): hydrophillic
drug
Lubricant :
magnesium sterate
Glidants :
Wetting agent :
Disintegrants :
Stabilizers :
4. (incompatibilities)
- hard capsule
aldehydes cross-link
- starch Mg oxide
- eutectic mixture
Mg carbonate kaolin
eutectic mixture
Part II
Soft gelatin capsules

,

-
-plasticizer glycerol
-(5-8% dry softgel, 30-40%w/w wetgel)
09/06/11
Page 94 of 126
soft gelatin capsules

compliance

cytotoxic
Visual inspection () 20

Uniformity of dosage unit
Content uniformity
Disintegration test
Dissolution test
Part II
Page 95 of 126
2.9 Powders and granules
1.
(Powder) :
( + )
(Granule) : powder particles form particle
( + + )
1. Active ingredient antacid, laxative

2. Diluents lactose, kaolin, talcum
3. Other flavoring agent, coloring agent
antibiotic dry syrup

acetylcysteine

(potent drug)
dose
O2
powder granule
1. Bulk powder or granules for internal use ()
non-toxic
segregation
- insufflation (snuff = )
- dentrifices
09/06/11
Part II
Page 96 of 126
- douche powders
2. Divided powder or granules (oral) for internal use ()
Effervescent salts dry mixture sodium bicarbonate, citric acid,
tartaric acid carbondioxide
Effervescent salts 2
1. Fusion method ():
All ingredient sieve No.60 heat 93-104C sieve No.4-10 dry 54C
2. Wet method ():

All ingredient + alcohol + sieve pack
!!!! calculation of sodium bicarbonate used in the effervescent formulation
Rx
200 g
252 g
162 g
Sodium bicarbonate
qs.
Citric acid
Tartaric acid
MW. Citric acid = 210.13
tartaric acid = 150.09
NaHCO3 = 84.01
3. Dusting powders for external use

- medicated dusting powder
Tolnaftate dusting powder PC
- sterile dusting powder
Chlorhexidine dusting powder BP
09/06/11
Part II
Page 97 of 126
1. Comminution ()
-Trituration :
-Pulverization by intervention :
-Levigation : semisolid slab spatula
2. Separation of particle size

3.Mixing
-Spatulation : spatula
-Tritulation :
-Sieving :
09/06/11
Part II
Page 98 of 126
2.10 Capsule
1.
2.
(Capsule)
unit dose
diluent (Gelatin)
Gelatin
Gelatin partial hydrolysis collagen
gelatin 2
1. Gelatin type A acid hydrolysis
2. Gelatin type B basic hydrolysis
-
-
-
-
-
-
-
Capsule
1. Hard gelatin capsule body () cap ()
2. Soft gelatin capsule gelatin shell 1
09/06/11
Part II
Page 99 of 126
Hard gelatin capsules

1.
Diluent : plug-forming 2
-soluble diluent (lactose) : hydrophobic drug
-Insoluble diluent(starch,MCC): hydrophillic drug
Lubricant : magnesium sterate
Glidants :
Wetting agent :
Disintegrants :
Stabilizers :
2.
000 5 0 5
65-1000 mg
3.
13-16% 10

30-45% Mg
stearate 1% hydrophobic bioavailability
sodium lauryl sulfate 1% bioavailability
4. (incompatibilities)
- hard capsule aldehydes
cross-link
- starch Mg oxide
- eutectic mixture Mg
carbonate kaolin eutectic mixture
09/06/11
Part II
Page 100 of 126
Soft gelatin capsules

,
, plasticizer glycerol, (5-8% dry softgel,
30-40%w/w wetgel)
soft gelatin capsules
-
- compliance
-
- cytotoxic
-
- Visual inspection () 20
- Uniformity of dosage unit

- Content uniformity
- Disintegration test
- Dissolution test
09/06/11
Part II
Page 101 of 126
Routeofadministration
Streiledosageform
Routeofadministration

Steriledosageform
Intravascular(i.v.)
vein:

1520

i.v.
1.i.v.infusion: fluid

2.i.v.push: vein

Subcutaneous(sc.)
( 1.5ml)
:
45
2426
09/06/11
Intracutaneous/Intradermal
Subcutaneous
Intramuscular
Intravascular
Intracardiac
Intraspinal
Intraartricular
Opthalmic
Intramuscular(i.m.)
iv

:
5ml
5ml

2ml
90
antibiotic,vitamin,iron,vaccine
- 2225
Intradermal(i.c.)
0.1ml
1015
localanesthesia, ,
Immunization
Part II

typeofpackaging
1.SmallVolumeParenteral(SVP)
- <100ml.
- solution,emulsion,suspension,drysolid
- singledoseampules
multipledosevials
prefilledsyring
(USP24)
1.
2.
3.
4.
5.
[Drug]Injection
[Drug] forInjection
[Drug] Injectableemulsion emulsion
[Drug]Injectablesuspension suspension
[Drug] forInjectablesuspension
suspension
(Aqueousvehicles)
SterilewaterforInjection(SWFI)
- WFI 1
-
-
- iv. isotonic
09/06/11
Page 102 of 126
2.LargeVolumeParenterals(LVP)
- >100ml.
- aqueoussolution,emulsion+/ drug
- Infusionfluid:NSS
TPN
Intravenousantibiotic
Patientcontrolledanalgesia:morphine
Dialysisfluids
Irrigationsolution

1. (Aqueousvehicles)
WaterforInjection(WFI)
-
- /reverseosmosis
- totalsolid 1mg/100ml
- 24
(Aqueousvehicles)
BacteriostaticWaterforInjection
- SWFI antimicrobialagent
- 30ml
- antimicrobialagent
-
Sodiumchlorideinjection(0.9%NaCl)
- isotonicsolution antimicrobialagent
-
Part II
(Aqueousvehicles)
BacteriostaticSodiumChlorideinjection
- sterileisotonicsolution NaCl
-
- 30ml
-
RingersInjection
- NaCl,KCl,CaCl2
- vehicle fluidelectrolyte
Page 103 of 126

2. (NonaqueousVehicles)
-
- fixedvegetableoil(soybean,
seasame,corn,oliveoil),glycerine,PEG,
alcohol
- mineraloil,paraffin
- im. iv.
Steriledosageform
2. (Dryheatsterile)
- (Hotairoven)
- + :160c 2
-
-
09/06/11
1. (Steamsterilization)
- (autoclave)
- ++
121c+15/ + 15
-
-
-

3. (filtration)
- (aqueoussol.)
- suspension,
-
-
- 0.22 0.45
Part II
4. (Gassterilization)
-
- ethyleneoxide(EO) Propyleneoxide
CO2
- 60%RH,5060c
- : (14)
mosmole
Osmol
=(W(g)/Mw)x ion
=molx ion
5. (Radiation)
- syring,catheter,
-
- gammaray,electronbeam
Ex1. mosmolarity 2liter

NaCl (MW58.44) 12g
CaCl2(MW110.99)
0.4g
Dextrose(MW198.17)
100g
1. osmol
NaCl =(12g/58.44)x2 =0.411
Osmolarity
=osmol/liter
=molarx ion
CaCl2=(0.4g/110.99)x3 =0.011
0.927 osmol
Dextrose=(100g/198.17)x1=0.505
Ex2. mosmolarity0.9%
NaCl(MW58.44)
2. mosmolarity
Osmolarity=0.927osmol/2liter
=0.464osmol/L
Mosmolarity=0.464x1000
=464mosmol/L
0.9%NaCl=0.9g/100ml =0.9g/0.1L
1. osmol NaCl
NaCl=(0.9g/58.44)x2
09/06/11
Page 104 of 126
=0.0308osmol
Part II
Page 105 of 126
2. mosmolarity
Osmolarity=0.0308osmol/0.1liter
=0.308osmol/L
Ophthalmic
preparation&technoly

Mosmolarity=0.308x1000
=308mosmol/L
Steriledosageform
Ophthalmicpreparation&technology

1.sterility
2.freefromforeignparticle
3.
4.Pyrogenfree
** Ophthalmicinjection
product
2.Preservative
Singledose,pt. ,
Multipledose

1. Benzalkoniumchloride(0.01%)
,
2.Combination :
Methylparaben(0.1%)+Propylparaben(0.02%)

09/06/11
6
1. (sterility) ***
>>
Autoclave,Dryheat
Filtration,Ethyleneoxide
steriledbyfiltration
3. (Vehicle)
Aqueoussystem Purifiedwater,WFI
Oilysystem Fixedoil
** Isotonic Buffersystem pH

1.Buffersystem discomfort, ,
Buffercapacity pH (7.4)
Part II

2.Isotonicsystem(Eq.to0.9%NaCl)
, 0.62%NaCl
hypertonicsolution
hypotonicsolution > >
USP VehicleofadjustpH
Boricacidvehicle
Boricacidvehicle+Additive
Isotonicphosphatevehicle
5.Packagingmaterial
SingleorMultipleapplicationunit
6.labeling 1
, Suspension Freeze
Page 106 of 126
4. (Additive)
ViscousorThickeningagent: contacttime,
,
Stabilizers: pH, antioxidant,
inertgas, EDTA, 10ml

Surfactants
Cosolvent
7
1. (Ophthalmicsolutions):
largevolume,smallvolume
1.Mixing
2.Filtration(0.8m) particle
3.Filling
4.Sterilization
1 > 2 > 3 > 4

1>2 > 4 >3
>> ,
, pyrogen
1. Drugandvehiclesterilization(sterile)
3.Powderforreconstitution < 2%
1. (+bulkingagent)>steriled>filling
2filtrationsterile>lyophilization>filling

2.Mixing
3.Filling

4. Ophthalmicointment contacttime,controlled
release,blurredvision
+ ( irritate, ,
T)
2Ophthalmicsuspension
***
( Aseptictechnique)
**
09/06/11
Part II
Ophthalmicointments(cont)
1.Drugandvehiclesterilization(sterile)
2.Mixingbycolloidmill
3.Filling
Page 107 of 126
7.Intraoculardosageform
, .

5. (Contactlens)
6. (Ocularinsert)
, ,controlled
release
ParenteralQualityControl
Steriledosageform
2.Claritytest()
**

fluorescent

USP ,

09/06/11
, ,

1.Leakertest

(0.51%Methyleneblue)>.>
2
**

1.

2. 1 ,

Part II
3.Sterilitytest

**
negativecontrol
Positivecontrol
2
1.Membranefiltration(0.45 )

> 14
2.Directtransfer ..
> 14 ( .. )
Page 108 of 126

Falsenegative

Falsepositive

..
4.Pyrogentest( )
Lysate clotting mechanism
Invivotest:
IV(T..
T )
Invitrotest endotoxin bacteria
LALtest 2
1.Gelclottechnique endotoxin
2Photometrictechnique() 2
2.1Turbidimetricmethod
endogenous
2.2substrateChromogenicmethod
*** monograph Gelclot
techniques
LALtest: endotoxin bact.
,
09/06/11
LAL Pro-clotting Enzyme* (inactive)
*
LAL reagent
Endotoxin
Divalent cation*
[Catalyst]
Heat labile and pH sensitive LAL pro-clotting enzyme (active)
(Ca2+,
Mg2+)
Coagulogen*
Coagulin (Clot protein)
5.Satetytest()
USP : 1723g
: 1

10 20+1g

Part II
Page 109 of 126
Sterile Dosage Forms

5

1. (Steam sterilization)
(autoclave)
/
+ ()+ 121
c + 15/+ 15
(
)
2. (Dry heat sterile)
(Hot air oven) + : 160 c 2

, glycerine,

3. (filtration)
/
suspension,
0.22 , 0.45 ( )
4. (Gas sterilization)

ethylene oxide (EO) Propylene oxide CO2
60% , 50-60 c
: (14 )
5. (Radiation)
syring, catheter, gamma ray, electron
beam
mosmole
Osmol
= (W(g)/Mw) x ion
= mol x ion
09/06/11
Part II
Page 110 of 126
Osmolarity
= osmol/ liter
= molar x ion
Ex1. mosmolarity 2 liter
NaCl (MW 58.44)
12 g
0.927 osmol
CaCl2 (MW 110.99)
0.4 g
Dextrose (MW 198.17)
100 g
1. osmol
NaCl
= (12g/58.44)x2
= 0.411
0.927 osmol
CaCl2
= (0.4g/110.99)x3
= 0.011
Dextrose
= (100g/198.17)x1 =0.505
2. mosmolarity
Osmolarity = 0.927 osmol/2liter
= 0.464 osmol/L
Mosmolarity = 0.464 x 1000
= 464 mosmol/L
Ex2. mosmolarity 0.9% NaCl (MW 58.44)
0.9% NaCl = 0.9 g/100 ml

= 0.9 g/0.1 L
1. osmol NaCl
NaCl
= (0.9g/58.44) x 2
= 0.0308 osmol
2. mosmolarity
Osmolarity = 0.0308 osmol/0.1 liter
= 0.308 osmol/L
Mosmolarity = 0.308 x 1000
= 308 mosmol/L
09/06/11
Part II
Page 111 of 126
Route of ministration

Intracutaneous/Intradermal dermis
Subcutaneous
dermis
Intramuscular
()
Intravascular
>>
Intracardiac
Intraspinal
spinal cord
Intra-artricular
Opthalmic
Intravascular (iv)
vein ()

15-20

i.v.
1. i.v. infusion : fluid
2. i.v. push : vein

Intramuscular (im)

:
5 ml

5 ml
2 ml
90 antibiotic, vitamin, iron,
vaccine
Subcutaneous (sc)
( 1.5ml)
: 45
09/06/11
Part II
Page 112 of 126
Intradermal (ic)
0.1 ml ()
10-15 local anesthesia,
, Immunization
type of packaging
1. Small Volume Parenteral (SVP)
- < 100 ml.
- solution,emulsion,suspension,dry solid
- single dose ampules :
multiple dose vials : vial
prefilled syring
: syring
cap lock
2. Large Volume Parenterals (LVP)
- > 100 ml.
- aqueous solution, emulsion /
- Infusion fluid
NSS
TPN
Intravenous antibiotic
Patient controlled analgesia morphine
Dialysis fluids
Irrigation solution

- (USP 24)
[Drug] Injection
[Drug] for Injection
[Drug] Injectable emulsion emulsion
[Drug] Injectable suspension suspension
[Drug] for Injectable suspension suspension
Vehicles
1. (Aqueous vehicles)
Water for Injection (WFI)
- ()
- /reverse osmosis
- total solid 1 mg/100 ml
09/06/11
Part II
Page 113 of 126
- 24
Sterile water for Injection (SWFI)
- WFI
- 1
-
- iv. isotonic
- Sterile Ampicillin Sodium,USP
Bacteriostatic Water for Injection
- SWFI antimicrobial agent ( )
- 30 ml
- antimicrobial agent
- SVP
- (: benzoyl alcohol)
Sodium chloride injection (0.9% NaCl)
- isotonic solution antimicrobial agent
-
Bacteriostatic Sodium Chloride injection
- sterile isotonic solution NaCl
-
- 30 ml
-
Ringers Injection
- NaCl,KCl,CaCl2
- vehicle fluid electrolyte
2. (Nonaqueous Vehicles)
-
- fixed vegetable oil (soybean, seasame,corn, olive oil), glycerine, PEG,
alcohol
- mineral oil, paraffin
- im. iv.
09/06/11
Part II
Page 114 of 126
2.11 5. IV abmixtures TPN

IV abmixtures :
(additive) 1 LVP IV
LVP
: NaCl inj., Dextrose inj., Lactated Ringer inj. etc.
Additive : Electrolyte, Antibiotic, Vitamin, Trace elements, Heparin, Insulin.
/ LVP
-Carbohydrate solution (Dextrose) : buffer, additive
-Electrolyte solution
-Monovalent (Na, K) : Compat
-Divalent (Ca, Mg) : Incompat Bicarb., Citrate, Phosphate
-Lactated, Acetate, Gluconate salt : buffer Additive
-Amino acid solution : , complex

*** Fat emulsion vehicle
*** IV admixture incompat LVP additive
IV admixture
Eq = wt(g) / Eq.wt ;
Eq.wt = MW/valency
Eq.wt = atomic wt. / valency
***Valency NaCl 1Na+ 1Cl-
Valency = 1
Ex. IV admixture D5W 500 mL K+ 15 mEq
6 g/30 mL KCl injection mL (MW; K=39, Cl=35.5)
mEq K+ = mg of KCl / Eq.wt
15 mEq
=
mg of KCl / (74.5 / 1)
mg of KCl
=
74.5*15
=
1,117.5 mg =
1.118 g
KCl injection 6 g/30 mL = 1 g /5 mL
KCl 1 g
5 mL
KCl 1.118 g
(1.118*5)/1 = 5.6 mL #Ans
TPN (Total Parenteral Nutrition)
09/06/11
Part II
Page 115 of 126
3
1. Multiple bottle system : fat, amino acid, dextrose
2. Two-in-one system (amino acid-glucose admixture) : fat, amino + dextrose
3. All-in-one system (3 in 1) :
TPN
1. 50% D/W
2. amino acid solution 50% D/W
3. phosphate (K2HPO4)
4. KCl, MTV, NaCl, Heparin, Trace element, MgSO4 etc.
5. Ca
6. ( )
7. 24
TPN
Rx
50% dextrose
200 mL
10% Amino acid
500 mL
NaCl
100 mEq
KCl
30 mEq
10% Ca gluconate
10 mL
K2HPO4
30 mEq
MgSO4
10 mEq
MVI
4 mL
50% Dextrose in water 500 ml 1000 mL

MVI (10 mL/ampule)
10% Ca gluconate (10 ml/ampule)
20% NaCl solution (3.4 mEq/mL)
KCl solution (2 mEq/mL)
K2HPO4 (1 mEq/mL)
50% MgSO4 (4 mEq/mL)
Aminosol 10 500 mL 10% amino acid with electrolyte
09/06/11
Part II
Na
K+
Mg2+
Acetate
ClH2PO4-
Page 116 of 126
48 mEq/mL
25 mEq/mL
5 mEq/mL
59 mEq/mL
62 mEq/mL
9 mEq/mL
1. 50% Dextrose in water = 200 mL

2. Aminosol 10 = 500 mL
3. 10% Ca gluconate = 10 mL
4. electrolyte trace element
electrolyte Aminosol 10 500 mL
Na+
48 mEq / 1000*500 = 24 mEq
K+
25 mEq / 1000*500 = 12.5 mEq
Mg2+
5 mEq / 1000*500 = 2.5 mEq
Cl
62 mEq / 1000*500 = 31 mEq
H2PO4
9 mEq / 1000*500 = 4.5 mEq
4.1 Phosphate (HPO4-)
Phosphate 30 mEq 30-4.5 = 25.5 mEq
K2HPO4 1 mEq/mL
K2HPO4 25.5 mL
4.2 K+
K+ 60 mEq ( KCl 30 mEq K2HPO4 30 mEq)
Aminosol 10 12.5 mEq K2HPO4 25.5 mEq
60-(12.5+25.5) = 22 mEq
KCl 2 mEq/mL
KCl = 11 mL
4.3 Cl Cl- 30 mEq ( NaCl 100 mEq KCl 30 mEq)
Aminosol 10 31 mEq KCl 22 mEq
130-(31+22) = 77 mEq
*** Cl- NaCl
Na+
09/06/11
Part II
Page 117 of 126
4.4 Na
Na+ 100 mEq
Aminosol 10 24 mEq
100-24 = 76 mEq
NaCl 3.4 mEq/mL
NaCl = 76/3.4 = 22.35 mL
*** NaCl 22.35 mL Cl- 76 mEq
Cl- = 31+22+76 = 129 mEq
130 mEq
4.5 Mg2+
Mg2+ 10 mEq
Aminosol 10 2.5 mEq
10-2.5 = 7.5 mEq
MgSO4 4 mEq/mL
MgSO4 = 7.5/4 = 1.88 mL
incompatability Ca Phosphate
-pH monophasic calcium phosphate
K2HPO4 + Ca2+ Ca(H2PO4)2

- (4oC)
- Calcium & Phosphate
Ca : Phosphate
1:2
Ca + Phosphate
45 mEq/L
Ca x Phosphate
75 mmol/L
-Calcium salt calcium gluconate
-Phasphate salt organic phosphate glucose phosphate
Ca:Phosphate K2HPO4
- amino acid amino acid soluble complex
Ca & Phosphate free Ca & Phosphate amino acid
pH monophasic calcium phosphate
- Phosphate Ca monobasic
phosphate
- 24
09/06/11
Part II
Ophthalmic preparation and technology
Page 118 of 126
by tong030
(Cornea) **
2 Cornea absorption Non-cornea absorption
1. sterility
2. free from foreign particle
3.
4. Pyrogen free** Ophthalmic injection
product
6
1. (sterility) *** sterility test
>>
Moist heat 121oC 15 Ib/in2 15 , Dry heat
Filtration 0.22 m memb.filter, Ethylene oxide ,
steriled by filtration
2. Preservative
Single dose , pt. ,
Multiple dose

1. Benzalkonium chloride (0.01%) ,
2. Methyl paraben(0.1%)+Propyl paraben(0.02%) Combination
3. (Vehicle) Isotonic Buffer system pH

Aqueous system - Purified water , WFI
Oily system Fixed oil
1. Buffer system discomfort , ,

Buffer capacity pH (7.4)
2. Isotonic system(Eq.to 0.9% NaCl) , 0.6-2 % NaCl
- hypertonic solution -
- hypotonic solution
- > >
USP Vehicle of adjust pH
- Boric acid vehicle Isotonic (1.9-2%) , pH < 5 , buffer Neutralized
- Boric acid vehicle+Additive oxidation (Sodium sulfite)
oxidized physostigmine , Epinephrine
- Isotonic phosphate vehicle
4. (Additive)
09/06/11
Part II

Page 119 of 126
- (Viscous or Thickening agent) contact time , ,
.. MC , PVC ,hypromellose, PEG , Carbomer
- (Stabilizers) pH , antioxidant , inert gas , EDTA ,
10 ml
- (Surfactants) Suspension eg. Polysorbate 20
- (Cosolvent) eg. PEG
5. Packaging material Single or Multiple application unit
6. labeling 1 ( 2 wk)
, Suspension Freeze
7
1. (Ophthalmic solutions) large volume , small volume
1. Mixing ()
1 > 2 > 3 > 4
2. Filtration(0.8 m) particle
1>2 > 4 >3
3. Filling
4. Sterilization
2. (Ophthalmic suspension) ,
,
1. Drug and vehicle sterilization (sterile)
Aseptic technique
**
2. Mixing
3. Filling
(1nm-0.3m) >>irritated
3. (Powder for reconstitution) <2%
1. (+bulking agent) > steriled > filling
2 filtration sterile(vehicle)>lyophilization>filling
( 2 )
4. (Ophthalmic ointment) contact time , controlled release, blurred vision
+ ( irritate,, T)
1. Drug and vehicle sterilization (sterile)
2. Mixing by colloid mill
3. Filling
5. (Contact lens)-
6. (Ocular insert)
, , controlled release
7. (Intraocular dosage form) , .
09/06/11
Part II
Page 120 of 126
by Tong030
3 , ,
Leaker test, Clarity test, Sterility

test, Pyrogen test, bacterial endotoxin test, uniformity of weight, uniformity of content,
1. Leaker test()
- (0.5-1%Methylene blue) > .>
-

2. Clarity test ()
**
- fluorescent -

- USP ,
2
**
1.
> 10 m
> 25 m
SVI
6000
600/container
/container
LVI
25/mL
3/mL
Ophth
50/mL
5/mL
2. 1 ,

> 10 m
> 25 m
> 50 m
SVI
3000
300/container
/container
LVI
12/mL
2/mL
Ophth
50/mL
5/mL
2/mL
3.Sterility test () **
09/06/11
Part II
Page 121 of 126
1. negative control
( 14 >> )
2. Positive control
( 3 bact 5 >>)
2
1. Membrane filtration(0.45 )
> 14
2. (Direct transfer) ..
> 14 (..)
- ..
-

False negative
False positive
4. Pyrogen test ()
1. In vivo test : pyrogen
IV (T.. - T)
**..
2. In vitro test endotoxin bacteria
LAL test 2
2.1 Gel-clot technique () endotoxin
Lysate clotting mechanism
LAL Pro-clotting Enzyme* (inactive)
(Ca2+, Mg2+) Divalent cation* [Catalyst]
Endotoxin
*
LAL reagent
Heat labile and pH sensitive LAL pro-clotting enzyme (active)

Coagulogen*
Coagulin (Clot protein)
2.2 Photometric technique () 2

2.2.1 Turbidimetric method endogenous
09/06/11
Part II
Page 122 of 126
2.2.2 substrateChromogenic method synthetic

peptide chromogen complex*** monograph Gel-clot techniques
LAL test : endotoxin bact. ,
6. Satety test() USP : 17-23 g

1
10 20+1 g
7. Uniformity of weight ()
8. Uniformity of content ()
9.
09/06/11
Part II
Page 123 of 126
2.12 Aerosols

1. Aerosols
2. Aerosol
3. MDI DPI
Sols
Sols hydrosols
aerosols

Inhale
Inhaler
Pharmaceutical Inhalers
Asthma
Cystic fibrosis
Emphysema
Pneumonia
Diabetes
Pharmaceutical Aerosols

drug interaction
first pass metabolism ( bioavailability
)

09/06/11
Part II
Page 124 of 126
Inhalers*
Metered dose inhaler (MDI) dose
Dry powder inhaler (DPI)

Nebuliser
1.
2.
3. Antioxidant
4.
5.
1.
2.
3. Antioxidant
4.
5.
1.
2.
3.
4.
5.
MDI
MDI
propellant
Product concentrate
Valve and Actuator
container
1.
1.
2.
3.
4.
5.
6.
1.
2.
3.
propellant 11, HFA CFC
2.Product concentrate
Pressurized system
09/06/11
Part II
Page 125 of 126
Propellant
Surfactant-stabilize suspension formulation
Co-solvent formulation aid
Dispense micrograms to milligrams API per actuation
Small precise volume delivered (25-100 mcl)
3.
1.
2.
3.
4. Actuators
1.
2.
3.
4.
5.container
1.
2.
3.
MDI
1.
1.
2.
2.
3.
3.
Dry Powder Inhaler

powder
Inspiratory Efford()

(Carrier)
09/06/11
Part II
Page 126 of 126

DPI

30
Particle size > 10 microns upper airway

Particle size < 0.5 microns Exhalation
Particle size 1-5 microns lower airway

Nebuliser
Ultrasonic nebuliser
piezoelelectric crystal
Jet nebuiser
compressed chamber neburizer
liquid inlet tube venture effect
Nebuliser

09/06/11
PART III: Production

Facilities
Production Facilities
Part III
Page 1 of 10
3.1 Product Facility

1.
Production area
1) Clean up room
2) Preparation room
3) Aseptic room
4) Quarantine room
5) Quality control room
6) Finished and packaging room
1.Clean up room
-
-
- vinyl epoxy resin
-
- HEPA filter(high efficiency particulate air filter)
Class 100000
2.Preparation room
- aseptic room
- Clean up room aseptic room
- stainless steel
-
- disinfectant
- air lock Preparation room aseptic room
- UV
Class 10000
3.Aseptic room
- filtration , filling , sealing
-
- vinyl tile, epoxy detergent ,
disinfectant T-bar
06/09/11
Part III
Page 2 of 10
- , close circuit
- Laminar air flow hood
- air lock
- stainless steel
-
Class 100
4.Quarantine area
- product QC
-
- ventilation
Class 100000
5.QC room
-
-Sterility test Class 100
-QC
Class 100000
6. Finished and packaging room
-
-
- Quarantine room Finished room
Class 100000
1.
1.1 Prefilter
-
- , ,
1.2 Electrostatic precipitation
- prefilter
-
06/09/11
Part III
Page 3 of 10
- 1.3 High efficiency particulate air filter (HEPA filter)

- 0.3 99.97%
2.
- 45-55% RH freeze dry 15-30% RH material
- RH silica gel
- RH spray sterile water
- Thermo-hygrometer
3.
- 25
- Heater, air condition
4.
- aseptic room positive pressure
- steroid, hormone, penicillin negative pressure
- critical critical 0.05 in/wg
5.
- HEPA filter recirculation
- particle, control temp., humidity
- Recirculation rate particle
/
= (./) x 60
(.)

- Standard operating procedure
- critical (aseptic room) critical
- Detergent disinfectant solution 0.450.22
06/09/11
Part III
Page 4 of 10
Conc
Detergent
1.Stericol
Xylitol, anionic soap
1%
2.Teepol
Surfactant Na
0.1%
0.1-1%
alkyl benzene sulphate,

alcohol ether sulphate ,
alcohol ethoxylate
Disinfectant
1.Hypochlorite
Na hypochlorite
spore
Disinfectant
2.Vantocil R
Polymeric biguanide salt

0.10.5%
nonionic detergent
3.Savlon
Cetrimide
alcohol
chlorhexidine gluconate
0.5-1%
formaldehyde
HEPA
spore 70% RH
p-formaldehyde hot plate formaldehyde
06/09/11
p-formaldehyde 1kg/ 300 .. 9 .

Part III
Page 5 of 10
laminar HEPA

:
UV
- larminar
- 253.7 nm 20w/cm 15
larminar air flow
: 3
1.Horizontal flow HEPA
2.Vertical flow HEPA
3.Convergent flow
HEPA
1. dioctyl phthalate;dop 0.3
80-100mg/L smoke photometer
0.01%
2. HEPA HEPA
3. HEPA animometer 6
90 / +/- 20%
-
-
- microbiology
-
-
-
-
-
06/09/11
Part III
Page 6 of 10
-
- protocol, GMP
-
-
-
- Lamina Air Flow
-
-
-
-
-
-
-
-
-
-
-
Continuous synthetic filament polyester (Decron)
100% high density polyethylene fiber (Tyvek)
-
-
-
-

- pre-entry wash room
-
06/09/11
Part III
Page 7 of 10
- SOP
- aseptic room non-sterile
- air shower air lock aseptic room
2.

Ideal container for parenterals
-
-
- product
-
-
1. (Glass)
silicone dioxide oxide
Na, K, Ca, Mg, Al, B Fe 4
TypeI: Borosilicate glass
SiO2 80% Boron oxide 12% oxide

TypeII : Sodalime glass with surface treatment
SiO2 72-75% Boron oxide 7-10% oxide treat
sulfur dioxide silicone
syringe
vial 7
sterile solid , oily preparation LVP
06/09/11
Part III
Page 8 of 10
(autoclave)

TypeIII; Sodalime with limit alkalinity
TypeII treat sterile solid ,sterile nonaqueous solution
TypeI
TypeI

TypeNP(Non-parenteral): Sodalime
SiO2 75% 15% 10% oxide 1 %

1. alkaline
2.
3.
4.
2. (Plastic)
LVP NSS
3
1.Permeation gass vapour
2.Leaching
3.Sorption polyamide nylon
2.1Thermoplastic :
2.1.1 Polyethylene (Polyethylene: PE)

PE plasticizer
gas permeation air oxidation
sterilization
2.1.2 High density Polythene syringe infusion fluid
06/09/11
Part III
Page 9 of 10
gas permeation
autoclave
2.1.3 Polyvinyl chloride (PVC)
PE
infusion fluid plasticizer
gas PE autoclave
PVC PVC
HCl plasticizer
2.1.4 Polymethyl methacrylate (PMMA) aseptic screen, contact lens, heart-machine,
bone replacement

2.1.5 Polystyrene syringe

- PE PVC
- Ethylene oxide

- PE PVC
2.1.6 Polypropylene syringe packing film fluid irrigation

autoclave
2.1.7 Polyamide (Nylon) stringe packaging film
autoclave

2.2 Thermosetting
2.2.1 Phenol-formaldehyde (cap)

additive
autoclave
2.2.2 Urea-formaldehyde (cap)
06/09/11
Part III
Page 10 of 10
2.2.3 Melamine-formaldehyde
Plastic containers for parenteral
PVC
sterile
LVP

air contamination
3. (Rubber closure)
- multiple dose container
gas
- preservative preservative
-

4
1.Butyl rubber

2.Nitrile rubber additive
antimicrobial
3.Chloroprene rubber Nitrile rubber
4.Silicone rubber
By Numtan 045 & Aofty 009
06/09/11
PART IV: Quality Assurance

& Quality Control
Stability Testings
Quality
Assurance
Part IV
4.1
Page 1 of 9
Stability Testing

1. (chemical change)
a.
2. (physical change)
a.
b.
3. (pharmacological change)
a. polymorphism (
)
b. biological vaccine, antiserum
4. (toxicological change)
a. tetracycline ( mycin )
( ) ASA Salicylic acid

5. (microbiological change)
a.
Order of kinetics
Order of kinetics
1. Zero order kinetics
- ()
-
X = X0 - kt
(mol/L)
X0 (mol/L)
t
X
X0
06/09/11
shelf-life (t90%)
X0-X
slope = -k
-dX/dt
slope = k
Part IV
Page 2 of 9
Shelf-life (t90%) 100% 90% ( 10%)

t90% = (X0 X)/k = 0.1X0 /k
2. First order kinetics
-
X = X0e-kt
lnX
= lnX0 - kt
(mol/L)
X0 (mol/L)
t
shelf-life (t90%)
lnX
-dX/dt

slope = -k
slope = k
slope = k
Shelf-life (t90%) 100% 90% ( 10%)

t90% = - ln0.9/k
*** order regression ***
90% labeled amount

1. (Accelerated storage test)
- (
2 )
-
1.
zero-order plot X t, first order plot
lnX t
2. k lnk 1/T (T )
3. intercept lnA slope Ea/R Arrhenius
06/09/11
Part IV
Page 3 of 9
lnk = lnA - (Ea/RT)

4. k T ()
5. k shelf-life 95% (CI
95% 5% 95%
)

1.
- Arrhenius rate constant
k
= Ae (-Ea/RT)
ln k = ln A - Ea/RT
k
T
A Arrhenius
Ea
R (8.314 Jmol-1 K-1, 1.987 cal mol-1 K-1)
lnk
Intercept = lnA
slope = -Ea/R
Kelvin-1
- Arrhenius 10 oC 2-4
factor Q10
2. pH
- pH pH
rate profile pH
log K
pH

pH
06/09/11
Part IV
Page 4 of 9
3.
Hydrolysis
Oxidation
Ester, lactone, Amide,

lactam, Oxime, Imide
Phenol, Thiol,
Thioester, Ether, Ald.,
amine, carboxylic acid
Photolysis ( aromatic
06/09/11
-
- Organic solvent
- dry granulation direct
compression
- buffer pH
antioxidant
Part IV
Page 5 of 9
4.2 Quality Assurance

1) (GMP)
(Good Manufacturing Practice-GMP)

GMP
GMP

,,

GMP
HACCP (Hazards Analysis and Critical Control Points) ISO 9000
(GMP Certificate)

1. :
(
)
2. :

3. :

06/09/11
Part IV
Page 6 of 9
1. (Critical defect)

2. (Major defect)
15
3. (Mino defect)

GMP
-
- /
- >>>
1.

2.
3.
4.
5.
06/09/11
Part IV
Page 7 of 9
2) x-bar chart p-chart SQC(Statistical Quality Control;

)
Control Chart

Control Chart
Control Chart
1. (normal distribution)
2. ( autocorrelation in time)
+ 3SD 0.27%
2
Control Chart 99.73% 0.27%
+ 3SD 99.73%
Control Chart 99.73% confidence interval
( Statistical Quality Control ; Chapter 6)

Control Chart
1.
2. (99.73% + 3SD)
(0.27% + 3SD)
06/09/11
Part IV
Page 8 of 9
3. Control Chart mean SD

reject lot
Control Chart
1. SD
SD
+ 3SD
Mean(mg) SD(mg)
Lower
Upper
Z low
Z high Prob(outside)
100
10
90
110
-1
1
0.3173105
100
5
90
110
-2
2
0.0455001
100
2.5
90
110
-4
4
0.0000634
100
2
90
110
-5
5
0.0000006
100 mg 90 mg-100mg
2.

Mean(mg)
90
95
100
105
110
SD(mg)
2.5
2.5
2.5
2.5
2.5
Lower
90
90
90
90
90
Upper
110
110
110
110
110
Z low
0
-2
-4
-6
-8
Z high
8
3
4
2
0
Prob(outside)
0.5000000
0.0227501
0.0000634
0.0227501
0.5000000
Control Chart 2
1. Chart for variable
1.1 Precontrol Chart
1.2 Shewart Control Chart
Average Chart(X-bar Chart), Sigma Chart(SD Chart)
Range Chart
2. Attribute Chart / / /
2.1 Fraction Rejected Chart ; p-Chart
2.2 Fraction Nonconformities Chart ; c-Chart
06/09/11
Part IV
Page 9 of 9
X-bar Chart
-
- Upper Lower Control Limit
S.E. Standard Error N
NOTE!! S.E. S.D.
-
- 2
X-bar Chart
p-Chart
- incidence (p)
- SE p sample size N
- UCL LCL incidence UCL or LCL = incidence + 3 SE
- / N
- . A reject 0.1% 100

UCL
reject = 100 x 0.001 = 0.1 >>> Np
UCL =
06/09/11
COMPREHENSIVE
Comprehensive

CREATED BY PHARMACEUTICAL TECHNOLOGY DEPARTMENT STUDENTS Rx'29
Pg. 1
COMPREHENSIVE
1. Preformulation
1.1 Solubilization
1. 30% ethanol (e =25) 70% water (e =80)

1. 60.5
2. 63.5
3. 66.0
4. 65.5
5. 35.9
2. pH phenobarbital
phenobarbital sodium 1%w/v 25oC phenobarbital (SO) = 0.005
M, pKa = 7.41 MW= 254
1. 3.8
2. 10.6
3. 8.24
4. 5.00
5. 8.93
3. pH cocaine base ` cocain HCl
0.0294 M pKa =8.4 solubility of cocaine = 5x10-3
1. 7.4
2. 7.7
3. 8.0
4. 5.7
5. 5.4
Pg. 2
COMPREHENSIVE
4. sodium sulfacetamide
1. pH
2. pH
3. pH
4. pH
5.
5.
1. Ionization
2. Association
3. Hydration
4. Surfactant
5. 1,3,4
1.2 Partition
1. 20 50% tie
line bimodal 8.4 72.2 %w/w
500
1. 235
2. 15
3. 174
4. 326
5. 346
Pg. 3
COMPREHENSIVE
1.3 Buffer and Isotonicity

1. 12.5% D/W IV 50% D/W
1. 50% D/W 1 sterile water for injection 3
2. 50% D/W 1 water for injection 3
3. 50% D/W 1 sterile water for injection 4
4. 50% D/W 1 water for injection 4
5. 50% D/W 1 NSS 4
2. pilocapine nitrate (PN) 2.5% w/v 10 ml. 4% w/v PN
ophthalmic solution NaCl Tonicity 4% w/v PN
NaCl isotonic solution ( E-value PN = 0.23)
1. 6.25 ml. NaCl 0.0575 g.
2. 6.25 ml. NaCl 0.0325 g.
3. 3.75 ml. NaCl 0.0575 g.
4. 3.75 ml. NaCl 0.5750 g.
5. 6.25 ml. NaCl 0.8425 g.
3. (eutectic mixture)
1. Menthol Camphor
2. Camphor Salbutamol
3. Salbutamol Eucalyptus
4. Camphor Eucarlyptus
5. Menthol Sulfur
Pg. 4
COMPREHENSIVE
1.5 Rheology
1. rate of shear shear stress
1. Newtonian
2. Plastic
3. Pseudoplestic 4. Dilatant 5. Thixotropy
2. non-newtonian yield value
1. Pseudoplestic 2. Dilantant 3. Thixotropy
4. Plastic 5.
3. plastic
1. deflocculated suspension
2. flocculeted suspension
3. deflocculeted suspension
4. flocculeted suspension
5.
4. shear-thinning system
1. glycerin
2. polyethlene glycol
3. minerol oil
4. 2% sodium carboxymethylcellulose
5. 5% bentonite
5.
1. newtonian 2. bingham badies 3. pseudoplastic 4. dilatant 5. thixotropy
6. falling ball viscometer
1.
2. non-newtonian
3.
4. newtonian
5.
7. 2
1. Falling sphere viscometer
2. Cup & bob viscometer
3. Cone & plate viscometer
4. Stormer viscometer
5. Ostwald viscometer
8. Newtonian
1. Chloroform Water BP
Pg. 5
COMPREHENSIVE
2. Carbomer Jelly yield value

3. Benzoyl Peroxide Cream BP
4. Liquid paraffin oral Emulsion BP
5. Milk of magnesia
9. Specific viscosity
1. Newtonian flow
2. Plastic flow
3. Pseudoplastic flow
4. Dilatant flow
5. Creep flow
10. Topical steroid
1.Pseudoplastic flow with thixotropy
2. Dilantant flow with thixotropy
3.Pseudoplastic flow
4. Newtonian flow
5. Antithixotropy
Pg. 6
COMPREHENSIVE
1.6 Incompatibility
1. chemical incompatibility precipitation
A. alcohol Tragacanth
B. Na2SO4 camphor water
C. NaCl tonicity AgNO3 eye drop
1. A
2. B
3. B,C
4. A,B
2. incompatibility
Rx
Phenobarbital 250 mg
Simple syrup
1.
2.
3.
4.
5.
30 mL
Physical
Chemical
Physicochemical
Therapeutic chemical
Pharmacodynamic incompatibility
3. ascorbic acid
1.
2.
3. Polysterine ()
4. PVP
5. neutral
Pg. 7
COMPREHENSIVE

1. sucrose alcohol ( 47)
2. aqueous preparation ( 47)

A. FD&C No.26 lake
B. Erythrosine sodium
C. FD&C No.26
1. A.
2. B.
3. C.
4. A,B
5. A,B,C
3. ( 49)
1. Tartrazine
2. FD&C No.6
3. FD&C No.5 lake
1. A.
2. B.
3. C.
4. A,B
5. A,B,C
4. glycerin ( 49)
Rhubarb
..
Glycerin
100 ml
Alcohol
qs
1000 ml
1. Preservative
2. Sweetener
3. tannin
5. preservative
A. Benzoic acid
B. Sodium benzoate
C. Dehydroacetic acid
1. A.
2. B.
3. A,B
4. A,C
5. A,B,C
Pg. 8
COMPREHENSIVE
6-7
A aldehyde derivative O2 pH 4.2
alcohol, glycerin, (freely soluble 1:2)

6. antioxidant oxidation
1. BHA
2. Sodium benzoate
3. EDTA
4. sodium metasulfide
5. sodium bisulfide
7. preservative syrup A
1. sodium benzoate
2. benzalkonium chloride
3. chlorhexidine gluconate
4. chloroxylenol
5. benzyl alcohol
1.8 Polymorphism and Eutectics

1. Eutectic mixture
1. Menthol & Camphor
2. Camphor & Salbutamol
3. Salbutamol & Eucalyptus
4. Camphor & Eucalyptus
5. Menthol & Sulfur
Pg. 9
COMPREHENSIVE
2. Polymorph
1. Polymorph
2. Polymorph
3. Polymorph
4. Polymorph
5. Polymorph amorphous
3.
1. enantiotropic polymorph polymorph
2. Polymorph
3. Recrystallization
4. Eutectic mixture
5. Eutectics 1
Pg. 10
COMPREHENSIVE
1.9 Adsorption and Interfacial Phenomena

1.
1.
2.
3.
4. Capillary rise method surface tension interface tension
5. The DuNouy Ring method surface tension interface tension
2. Adsorption isotherm type 2
1.
2.
3.
4.
5.
Pg. 11
COMPREHENSIVE
3.
3.1 4
1. 0.04 dyne/cm
2. 0.39 dyne/cm
3. 3.92 dyne/cm
4. 39.2 dyne/cm
5. 392 dyne/cm
3.2
10 cm
1. 3.92 dyne/cm
2. 39.2 dyne/cm
3. 392 dyne/cm
4. 3920 dyne/cm
5. 39200 dyne/cm
Pg. 12
COMPREHENSIVE
2. Pharmaceutical Dosage Forms

2.1 Solutions (Solutions,Aromatic waters,Syrups,Elixirs,Tinctures,Fluid
extracts,Spirits)
1.
Rx
Ammonium bicarbonate
25 ml
Strong Ammonia Solution
67.5 ml
Nutmeg oil
0.3 ml
Lemon oil
0.5 ml
Alc(90%)
37.5 ml
Distilled water to
1000 ml
1. Aromatic water
2. Elixir
3. Solution
4. Spirit
Pg. 13
COMPREHENSIVE
2 , 3
A Aldehyde derivative O2 pH 4.2
alcohol , glycerin ( Free soluble 1 :2 )
2. Preservative A
1. Sodium benzoate
2. Benzalkonium Chloride
3. Chlorhexidine Gluconate
4. Chloroxylenol
5. Benzyl alcohol
3. Antioxidant Oxidation
1. BHA
2. Sodium benzoate
3. EDTA
4. Sodium metabisulfide
5. Sodium bisulfate
4. Emulsifier
1.
2.
3.
4.
5.
Tragacanth
Acacia
Caraya gum
Indian gum
Stereulia gum
Pg. 14
COMPREHENSIVE
2.2 Colloids (Milk, Magma, Gel, Mucilage Mixture)

1. Colloids
1. 0.5 micron 1 nm
2. Tyndal effect
3. Brownian
4. dialysis semi-permeable membrane
5.
2. Lyophilic colloids
A : pH hydrophilic colloids
B : salting out electrolyte salt valency
C : colloids
1. A B
2. A C
3. B C
4. A, B C
5.
3. Colloids molecule
Colloids micelle
1. Lyophilic colloid
2. Lyophobic colloid
3. Associate colloid
4. Lyophobic colloid Associate colloid
5.
Pg. 15
COMPREHENSIVE
4. MC
1.
2.
3.
4.
5.
2.3 Suspensions
1. Sulfadiazine 1.5 g/ml 2.6 m rate of
sedimentation g=980 =0.009 poise
1. 2.05x104
2. 2.05x10-4 cm
4. 7.86x10-3
3. 7.86x103
5. 6.13x10-4 cm
2.
degree of flocculation B
1. 1
2. 2
3. 3
4. 4
5. 5
Pg. 16
COMPREHENSIVE
3. F (sedimentation volume) 1
A. =
B. = 1
C. flocculation equilibrium
1. A
2. B
3. C
4. A&B
5. A&C
2.4 Emulsions
1. emulsion
1. Flocculation and creaming
2. Coalescence and breaking
3. Flocculation and caking
4. Deterioration and microorganism
5. phase inversion
2. emulsion mineral oil acacia dry gum method
1. mineral oil acacia mucilage

2. acacia mineral oil
5. mineral oil
3. benzoic acid o/w emulsion
A. Partition coefficient
B. Dissociation constant
C. Critical micelle concentration
1. A
2. B
3. C
4. A,B
5. A,B,C
Pg. 17
COMPREHENSIVE
4. Mineral oil emulsion emulsifier (Span 80 Tween

80) 40/60 HLB Span 80 = 4.3, Tween 80 = 15 HLB
5. zinc oxide, calamine 8 mg olive oil, Ca(OH)2

100 ml
1. Wet gum method
2. Dry gum method
3. In situ soap method
4. Bottle method
5. Suspension method
6. Pharmagel A
1. Auxilliary method
2.
3. methylcellulose
4. Pharmagel A heat 100 20
5. Homoginizer
7. phase reversion
1. emulsifying agent
2.
3. phase volume ratio
4. internal phase external phase
5. external phase internal phase
Pg. 18
COMPREHENSIVE
8. mineral oil 0.2%, rose oil, water rose oil, borax,

glycerine, cetyl alcohol
1. emulsifying agent phase oil
2. emulsifying agent phase
3. rose oil water rose oil
4. borax phase
5. borax phase oil
9. dry gum method primary emulsion
1.
2.
3. crakling
sound
10. creaming o/w emulsion
1. downward creaming
2. Film emulsifying agent oil
3. oil
4. irreversible process
5. oil cream
11. o/w very water soluble
12. Dry gum method
Pg. 19
COMPREHENSIVE
2.5 Semisolid dosage forms (Ointments, Creams, Pastes, Jellies)

1. topical steroid topical steroid
1. Hydrocarbon base
2. Oleaginous base
3. Absorption base
4. O/W emulsion base
5. W/o emulsion base
2. Ointment each g contains : betamethasone 0.5 mg and salicylic acid 30
mg in paraben freez ointment base of white petroleum and mineral oil
ointment base
1. Water soluble ointment base
2. Oleaginous ointment base
3. Emulsion ointment base
4. Absorption ointment base
5. Acidic ointment base
3. sorbitan monostearate tween 80
Rx
Liquid paraffin
35
Wool fat
1
Cetyl alcohol
10
Emulsifier
7
Purified water to
100
M.ft. cream (o/w)
Pg. 20
COMPREHENSIVE
required HLB 12.18 sorbitan monostearate

tween 80 HLB 4.3 15
1. sorbitan monostearate 1.84 Tween 80 5.16
2.6 Suppositories
1. (, ?)
2. Aescin
3. PEG 400 0.5% PEG 4000:PEG 1500=6.4

1. Reinforcing filter
2. Opacifier
3. Plasticizer 4. Coloring agent
5. Preservative
4. Theobroma oil
Aspirin
0.2 g
Theobroma oil qs
M.ft. rectal suppo 10
Aspirin=3.0 g/ml, Theobroma oil=0.9 g/ml, Blank weight=2.2
1. 20.1
2. 20.9
3. 21.4
4. 21.94
5. 22.0
Pg. 21
COMPREHENSIVE
5. rectal suppositories
1. 0.1 N HCl
2. 2.0 N HCl
3. Citric acid buffer pH 4.5
4. Purified water
5. Phosphate buffer pH 8.0
6. Suppository base rectal fluid
A. Cocoa butter
B. Propylethylene glycol
C. Glycerol-gelatin base
1. A
2. B
3. C
4. A,B
5. B,C
2.7 Tablets
1.
1.
2.
3.
4.
5.
Lactose
Magnesium sulfate
Microcrystalline cellulose
Corn starch
Sodium lauryl sulfate
2. binding
1. Motting
2. Straitation
3. Cracking
Pg. 22
COMPREHENSIVE
4. Motting Cracking
5. Straitation Cracking
3.
A. Lactose
B. Starch
C. Calcium phosphate
D. Microcrystalline cellulose
1. A C
2. C
3. C D
4. D
5. B , C D
4. filming
1. Capping
2. Binding
3. Laminating
4. Chipping
5. Picking
Pg. 23
COMPREHENSIVE
2.8 Modified Release Dosage form (Include Polymers)

1. sustained release
A (dose dumping)
B osmotic pump
C
1. A
2. B
3. C
4. A,C
5. B,C
2. Physically controlled system

1. Ionic strength
2. Ultrasound
3. Pump systems
4. Osmotic pressure
5.Polymer swelling
3. controlled release
1.
2.
3.
4.
5.
Pg. 24
COMPREHENSIVE

1. calculation of sodium bicarbonate used in the effervescent formulation
Rx
200 g
252 g
162 g
Sodium bicarbonate
qs.
Citric acid
Tartaric acid
MW. Citric acid = 210.13
tartaric acid = 150.09
Sodium bicarbonate =
NaHCO3 = 84.01
2.
1. 0 1
2.
3.
4. cap body
5. enteric coated pellet
Pg. 25
COMPREHENSIVE
3. soft gelatin
1.
2.
3.
4. plate process
5. semisolid
4. ( fusion )
1.
2. citric acid
3. tartaric acid
4. Glycerin
5. alcohol
2.11 Sterile Dosage forms

1. multiple dose
1. small volume parenteral
2. 30 ml
3. antibiotic preservstive
4. clarity test
5. ampule vial
2.
Rx
Boric acid
1.24 g
Sodium borate
0.02 g
NaCl
0.29 g
Water qs
100
mL
NaCl = 58 Osmolarity
Pg. 26

1. 50
2. 100
3.
1. Tonicity
2. pH
COMPREHENSIVE
3. 200
4. 400
5. 500
3. Viscosity
4. Buffer
5. no foreign particle
4. NaCl
1. Isotonic
2. preservative
3.
4. pH Solution
5.
5. Acidosis sodium bicarbonate sodium bicarb
2.8 mmol/L SWFI 100 mL
Na.bicarb ampule
Na.bicarb 5 mL/amp 2 mg/mL (MW Na = 23 , H =1 ,
C=12,O=16)
1. 2 amp
2. 3 amp
3. 4 amp
4. 5 amp
5. 6 amp
6.
1. Clean room class 10
2. Clean room class 100
3. Clean room class 1,000
7.
Pg. 27
COMPREHENSIVE
1. Sterility
2. Osmolarity
3. Microbial limit test
4. Particular matter
5. Preservative
8.
1. Solution
2. Jelly
3. Suspension
4. Emulsion
5.Coalescence
9. LAL
10. 0.5% Atropine sulfate ED

7% atropine sulfate solution 0.7% NaCl
Atropine sulfate 0.5 g
NaCl
8.3 g
H2O
100mL
1. Hypotonic solution
2. Hypertonic solution
3. Isotonic solution
4. Atropine sulfate
5. ^^
11.
1. Solution
2. Suspension 3. Ointment 4. Cream
5. Ocular insert
Pg. 28
COMPREHENSIVE
12.
1. 170oC 2
2.
3. sterile membrane
4. LAL test
5. E.coli 10 cfc/mL
13.
14.
1. Isotonic agent
2. Preservative
3. Buffering agent
4. Antiadhesive
5. Viscosity additive
15. Ophthalmic solution
1. ionic strength
2. Sterility
3. Isotonicity 4. Preservative 5.
Viscosity
16. Preservative
1. Benzalkonium chloride
2. Paraben
3. Sodium metabisulfite
4. Benzoic acid
5. BHT
Pg. 29
COMPREHENSIVE
17. Ciprofloxacin extemporaneous eye drop
1. NSS
2.WFI
3. Deionized water
4. Purified water
5. Water for irrigation
18.
1. Sterile technique
2. Aseptic technique
3. Non sterile technique
4. UV technique
5. Pasteurized technique
19.
1.
2. 0.2 NaCl
3. 0.9 NaCl
4. 1.2 NaCl
5. 3 , 4
20. SWFI USP 23

1. autoclave 2. Isotonic
3. Non-pyroge 4. No preservative
5.
21. Oily vehicle

A. Vegetable oil
B. Mineral oil
C. Animal oil
1. A
2. B
3. C
4. A,B
5. B,C
Pg. 30
COMPREHENSIVE
22. Chlortetracycline HCl Ophthalmic ointment

1. Autoclave
2. Dry heat sterilization
3. Sterilization filtration
4. Gas sterilization
5. Ionized radiation
23.Preservative Fluorescine
1. Benzalkonium chloride
2. Chlorobutanol
3. Thiourasal
4. Paraben
24. sterility test penicillin injection USP 23

1. Positive control Sterility media
2. Negative control growth
3. activity sample enzyme penicillinase
4. Medium Fluid thioglycolate Soybean casein digest media
5. Sterility membrane filtration
25. Boric acid eye lotion
.

Pg. 31
COMPREHENSIVE
26. SVP
1. Single dose
2. Multiple dose
3. Ampoule or Vial
4. 1,3
5. 3
27. oil vehicle
A Autoclave
B
C Oil
1. A
2. A,B
3. A,C
4. B,C
5. A,B,C
28. Moist heat sterilization

A : Oxidation
B : Protein coagulation at cell wall
C : Protein denature
D :
1. A,B
2. B,C
3. C,D
4. B,C,D
5. A,B,C,D
29.
1. Moist heat
2. Dry heat
3. Gas sterilization
4. Membrane filtration
5. Radiation
Pg. 32
COMPREHENSIVE
30. Preservative
1. Bacteriostatic WFI
2. Multiple dose for Injection
3. LVP for injection
4. Eye drop 5-10 ml
5. Reconstitute suspension
31. Ampoule
1. pyrogen test
2. Sterility test
3. Preservative efficacy
4. Clarity test
5. leaker test
32. IM
A solution
B Suspension
C Emulsion
1. A
2. B
3. C
4. B,C
5. A,B,C
33. IV solution G 5% w/v Dextrose monohydrate 0.18%w/v

NaCl total Osmolar concentration mOsm/L
MW Dextrose monohydrate = 198.2 , MW NaCl = 58.5
1. 31.4
2. 62
3. 283
4. 314
5. 923.8
Pg. 33
COMPREHENSIVE
2.12 Aerosols
1. aerosol
A.
B. systemic
C. alveoli
1. A
2. A, B
3. A, B, C
4. A, C
5. C
2. aerosol
1. binder
2. surfactant 3. lubricant
4. active ingredient
5. propellant
3. TPN two-in-one system

dextrose-amino acid admixture
A. order of mixing
B. pH
C. temperature
1. A
2. A, B
3. A, B, C
4. A, C
5. C
4. Intravenous solution A 0.18% w/v NaCl 5% w/v Dextrose

monohydrate total osmolar concentration mOsm/L
(MW; NaCl=58.5, Dextrose monohydrate=198.2)
1. 31.4
2. 62
3. 283
4. 314
5. 252
Pg. 34
COMPREHENSIVE
3. Production facilities
3.1 Production facilities
1. large volume parenteral
preparation
A. ,
B.
C.
1. A
2. B
3. C
4. A+B
5. B+C
2. nitroglycerine
3. Ascorbic acid
4. Multivitamin syrup
1.
2.
3.
4.
5. neutral glass
5.
1. caffeine
2. morphine 3. hyoscine
4. pilocarpine 5. Ephedrine
Pg. 35
COMPREHENSIVE
4. Quality Assurance and Quality Control

4.1 Stability Testing
1. Ascorbic acid
A
200 mg
0
6
12
36
200
194
188
164
B
200 mg (
18%)
236
230
224
200
C
10 mg
10
9
8
5
1. 3 zero order
2. 3 zero order B
3. 3 first order
4. 3 first order B
5. 3 second order
2. A maximum pH stability rate constant
1. -9
log K
s-1
2. 10 -9 s-1
-7
3. 10 7 s-1
-8
4. 10 -6 s-1
-9
pH
5. 10 6 s-1
Pg. 36
COMPREHENSIVE
3. aspirin tab
aspirin
Conc.
Product A
Product B
Product C
Aspirin
Time
1. Product A
2. Product B
3. Product C
4.
5.
4. A hydrolysis
A
1. complexing agent
2. pH pKa
3.
4. cosolvent
5. lyophilized powder
5. simvastatin first order K1 =
0.0005 hr-1 shelf life
1. 1347 hr
2. 550 hr
3. 168 hr
4. 210 hr
5. 150 hr
6. ....
Pg. 37
COMPREHENSIVE
1. 90%
2. 50%
3. 1%
4. 90-110 %LA
5. 5 2

1. Validation GMP
A.
B.
C.
1. A,B
2. B,C
3. A,C
4. A,B,C
5. A
2. GMP
A. Quality area
B.
C. First in-First out
1. A
2. B
3. C
4. A,B
5. B,C
Pg. 38
COMPREHENSIVE
3. GMP 2
A.
B. Penicillin
C. Potent drug
1. A
2. B
3. C
4. A,B
5. B,C
4. GMP GMP
1.
2.
3.
4.
5.
5. GMP
A. 2
B. Quaranteen area
C.
1. A
2. B
3. B,C
4. A,C
5. A,B,C
Pg. 39
COMPREHENSIVE
SQC
6. % CV = 2.11 in-process control
10 100 mg
UCL LCL
1. 90.00 100.00%
2. 95.00 105.00%
3. 97.89 102.11%
4. 98.00 102.00%
5. 99.30 100.70%
Pg. 40
COMPREHENSIVE
Comprehensive

Pg. 41
1. Preformulation
9. 1
10. 3
1.1 Solubilization
1. 2
1.6 Incompatibility
1. 1
2. 3
2. 1
3. 2
3. 5
4. 4
5. 5
1.2 Partition
3. 4
1.3 Buffer and Isotonicity
6. 4
2. 2
7. 1
3. 1
1.5 Rheology
3. 2
4. 2
5.
1. 1
2. 4
1. incomplete solution
2. 1
1. 2
1. 2
COMPREHENSIVE
1.8 Polymorphism and Eutectics

1. 1
2. 2
3. 2
4. 4
1.9 Adsorption and Interfacial
5. 4
Phenomena
6. 4
7. 3
8. 1
1. 4
2. 2
3.1 4
= fb/2L
Pg. 42

= mg/2L
=
=
2.2 Colloids (Milk, Magma, Gel,

Mucilage Mixture)
(4 g )(0.98m / s 2 )
2 x5cm
2
(4 g )(0.98 x10 cm / s )
2 x5cm
= 39.2 dyne/cm
3.2 4
1. 4

dialysis semi-permeable membrane

dialysis semi-permeable
W = A
membrane
A; A = 2L s =
2. 4
2 x 5cm x 10cm = 100cm2
3. 3
W = A
4. 1
MC
= 39.2 dyne/cm x 100cm2
= 3920 dyne/cm
MC
ergs/cm2
MC
2. Pharmaceutical Dosage Forms
2.3 Suspensions
2.1 Solutions (Solutions,Aromatic

waters,Syrups,Elixirs,Tinctures,Fluid
1. 2
extracts,Spirits)
3. 5
2. 3
2.4 Emulsions
1. 3
2. 1
3. 4
4. 4
COMPREHENSIVE
1. 3
2. 2
3. 4
4. 10.7
Pg. 43
COMPREHENSIVE
5. 3
2.8 Modified Release Dosage form
6. 5
(Include Polymers)
7. 4
8. 4
1. 5
9. 2
2. 5
10. 5
3. 1
11. Incoperation
12. gum oil
2.5 Semisolid dosage forms

(Ointments, Creams, Pastes, Jellies)
1. Sodium bicarbonate 282.1 + 194.3 =

476.4 g
2. 4
3. 4
1. 4
4. 2
2. 2
3. 1
2.11 Sterile Dosage forms

2.6 Suppositories
1. Fusion ()
2. ( permeability)
3. 1
8.
2.7 Tablets
4. 5
4. 1
7. 3
6. 5
3. 3
3. 3
6. 4
5.
2. 5
2. 2
5. 2
4. 3
1. 4
1. 4
9.
10. 1
11. 4
12. 3
13. 1
Pg. 44

14. 4
COMPREHENSIVE
3.1 Production facilities
15. 1
1. 5
16. 1
2.
17. 2
3.
18. 1
4. 4
19. 2
5. 1
20. 5
21. 5
4. Quality Assurance
22. Ionized radiation
and Quality Control
23. 1
24. 5
4.1 Stability Testing
25. > > > , Autoclave

26. 4
1. 1
27. 3
2. 2
28. 2
3. 1
29. 1
4. 3
30. LVP for injection
5. 4
31. 3
6. 1
32. 5
33. 4
2.12 Aerosols
1. 4
2. 3
3. 3
1. 4
4. 4
2. 5
3. Production facilities
Pg. 45
COMPREHENSIVE
3. 4
4. 2
5. 5
6. 4
Pg. 46

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C mpr

mix = (wt. fraction of A) A + (wt. fraction of B) B

mix = (30/100) 25 + (70/100) 80

Created by Pharmacy Student. Department of Pharmaceutical Technology PSU Rx'29

Created by Pharmacy Student. Department of Pharmaceutical Technology PSU Rx'29

Phosphatidyl choline (Lecithin)

Polar: -OH, -O-,

FICKS FIRST LAW OF DIFFUSION

W/O emulsifying agents

A = surface area of solute

Created by Pharmacy Student. Department of Pharmaceutical Technology PSU Rx'29

H2O, alcohol C = 2 Fmax = 3

% w/w of phenol in water

Created by Pharmacy Student. Department of Pharmaceutical Technology PSU Rx'29

% w/w of phenol in water

critical solution temperature

% w/w of phenol in water

% w/w of Nicotine in water

% w/w of TEA in water

% w/w of Phenol in water

Created by Pharmacy Student. Department of Pharmaceutical Technology PSU Rx'29

Fmax = 4 ( T, P, conc1, conc2)

Created by Pharmacy Student. Department of Pharmaceutical Technology PSU Rx'29

Created by Pharmacy Student. Department of Pharmaceutical Technology PSU Rx'29

polarity dielectric constant :

Created by Pharmacy Student. Department of Pharmaceutical Technology PSU Rx'29

mix = (wt. fraction of A) A + (wt. fraction of B) B

: 30% ethanol ( =25) 70%

Created by Pharmacy Student. Department of Pharmaceutical Technology PSU Rx'29

: Sodium lauryl Sulfate

- Cationic Surfactants : Alkyl ammonium , Alkyl trimethylammonium

Created by Pharmacy Student. Department of Pharmaceutical Technology PSU Rx'29

Created by Pharmacy Student. Department of Pharmaceutical Technology PSU Rx'29

FICKS FIRST LAW OF DIFFUSION

D = Diffusion coefficient of solute

Created by Pharmacy Student. Department of Pharmaceutical Technology PSU Rx'29

1. Complete miscibility : -alcohol, benzene-CCl4

(Phase Equilbria and The Phase Rule)

Created by Pharmacy Student. Department of Pharmaceutical Technology PSU Rx'29

Created by Pharmacy Student. Department of Pharmaceutical Technology PSU Rx'29

Created by Pharmacy Student. Department of Pharmaceutical Technology PSU Rx'29

Created by Pharmacy Student. Department of Pharmaceutical Technology PSU Rx'29

Created by Pharmacy Student. Department of Pharmaceutical Technology PSU Rx'29

Created by Pharmacy Student. Department of Pharmaceutical Technology PSU Rx'29

Created by Pharmacy Student. Department of Pharmaceutical Technology PSU Rx'29

Created by Pharmacy Student. Department of Pharmaceutical Technology PSU Rx'29

Created by Pharmacy Student. Department of Pharmaceutical Technology PSU Rx'29

20oC 50 % tie line

Created by Pharmacy Student. Department of Pharmaceutical Technology PSU Rx'29

Created by Pharmacy Student. Department of Pharmaceutical Technology PSU Rx'29

1 (plotting on the side)

Created by Pharmacy Student. Department of Pharmaceutical Technology PSU Rx'29

Created by Pharmacy Student. Department of Pharmaceutical Technology PSU Rx'29

Created by Pharmacy Student. Department of Pharmaceutical Technology PSU Rx'29

2) Salvation of hydration (.)

: mhos Siemens (S)

Created by Pharmacy Student. Department of Pharmaceutical Technology PSU Rx'29

-equivalent conductance () = . 1 g cell

Created by Pharmacy Student. Department of Pharmaceutical Technology PSU Rx'29

* Vant Hoff Arrhenius electrolyte

Created by Pharmacy Student. Department of Pharmaceutical Technology PSU Rx'29

Created by Pharmacy Student. Department of Pharmaceutical Technology PSU Rx'29

- Weak base + its salt:

pOH pKb log