Presentation On GEA Courtoy

Presented by
Presenter : Sangram kendre
Email Id : sangamkendre@gmail.com
• Tablets are solid dosage for
ms consisting of active ingr
edient(s) and suitable phar
maceutical excipients. They
may vary in size, shape, wei
ght, hardness, thickness, di
sintegration and dissolution
characteristics, and in other
aspects. They may be class
yfied, according to the meth
od of manufacture, as comp
ressed tablets or molded ta
blets.
 Advantages
• Production aspect
– Large scale production at l
owest cost
– Easiest and cheapest to pa
ckage and ship
– High stability
• User aspect (doctor, pharmaci
st, patient)
– Easy to handling
– Lightest and most compact
– Greatest dose precision & l
east content variability
Disadvantages
• Some drugs resist compressio
n into dense compacts
• Drugs with poor wetting, slow
dissolution, intermediate to lar
ge dosages may be difficult or i
mpossible to formulate and ma
nufacture as a tablet that provi
de adequate or full drug bioava
ilability
• Bitter taste drugs, drugs with a
n objectionable odor, or sensiti
ve to oxygen or moisture may r
equire encapsulation or entrap
ment prior to compression or t
he tablets may require coating
 Types of tablets
• 1)compressed tablets
• 2)sugar coated tablets
• 3)film coated tablets
• 4)enteric coated tablets
• 5)effervescent tablets
• 6)chewable tablets
• 7)dispersible tablets
• 8)sustained release tablets
• 9)multilayer tablets
• 10)sublingual tablets
• 11)toroches
• 12)buccal tablets
• 13)implant tablets
• 14)hypodermic tablets
• 15)solution tabletc
• 16)vaginal tablets
EXCIPIENTS FOR COMPRESSED TABL
ETS
Compressed tablets usually contain a number of pharmac
eutical adjuncts, known as excipients, in addition to the m
edicinal substance. The use of appropriate excipients is i
mportant in the development of the optimum tablets. Exci
pients determine the bulk of the final product in dosage fo
rms such as tablet, capsule, etc., the speed of disintegrati
on, rate of dissolution,release of drug, protection against
moisture, stability during storage, and compatibility . Exci
pients should have no bioactivity, no reaction with the dru
g substance, no effect on the functions of other excipient
s, and no support of microbiological growth in the product
.
 A. DILUENTS

Diluents increase the volume to a formulation to pr

epare tablets of the desired size. Widely used fill
ers are lactose, dextrin, microcrystalline cellu-los
e starch, pregelatinized starch, powdered sucros
e, and calcium phosphate.
• The diluent is selected based on various factors, such as
the experience of the manufacturer in the preparation of
other tablets, its cost, and compatibility with other formul
ation ingredients. For example, in the preparation of tabl
ets or capsules of tetracycline antibiotics, a calcium salt
should not be used as a diluent since calcium interferes
with absorption of the antibiotics from the GI tract.
 B.BINDERS

• Binders promote the adhesion of particles of the formul

ation. Such adhesion enables preparation of granules a
nd maintains the integrity of the final tablet. As listed in
the Table, Commonly used binding agents include: star
ch, gelatin and sugars (sucrose, glucose, dextrose, and
lactose).
 Examples of Binders
Carboxymethylcellulose, sodium Karaya gum

Cellulose,microcrystalline(Avicel®) Starch, pregelatinized

Ethylcellulose Tragacanth gum

Hydroxypropyl methylcellulose Poly(acrylic acid)

Methylcellulose Polypvinylpyrrolidone
Acacia gum Gelatin
Agar Dextrin
Algin acid Glucose
Guar gum Molasses
 C. LUBRICANTS
• Lubricant is a substance capable of reducing or preventi
ng friction, heat, and wear when introduced as a film bet
ween solid surfaces. It works by coating on the surface o
f particles, and thus preventing adhesion of the tablet ma
terial to the dies and punches. Glycerylmonostearate(US
P/NFCH2(OH)CH(OH)CH2O2CC17H35) is one example
of a lubricant. Lubricants play more than one role in the p
reparation of tablets as described below.
• 1. Lubricants improve the flow of granules in the hopper t
o the die cavity.
• 2. Lubricants prevent sticking of tablet formulation to the
punches and dies during formulation.
• 3. Lubricants reduce the friction between the tablet and t
he die wall during the tablet’s ejection from the tablet ma
chine.
• 4. Lubricants give a sheen to the finished tablets.
• Commonly used lubricants include: talc, magnes
ium stearat, calcium stearate ,stearic acid, hydro
genated vegetable oils and (PEG).
 D. DISINTEGRATORS

• The breakup of the tablets to smaller particles is important for dis

solution of the drug and subsequent bioavailability. Disintegrators
promote such breakup. To rupture or breakup of tablets, disintegra
ting agents must swell or expand on exposure to aqueous solutio
n. Thus, the most effective disintegrating agents in most tablet sys
tems are those with the highest wa-ter uptake property. In general,
the more hydrophilic, the better disinte-grating agents are therefor
e highly hydrophilic. A list of typical disinte-grants is tabulated in T
able
 E. WETTING AGENTS
• Water molecules attract each other equally in all directions. Water m
olecules on the surface, however, can only be pulled into the bulk w
ater by water molecules underneath, since there are no water molec
ules to pull in the opposite direction. The surface tension of water is
strong enough to support the weight of tiny insects such as water str
iders. The surface ten-sion in action can be visualized by placing a s
mall drop of alcohol on a thin layer of water. Alcohol with lower surfa
ce tension mixes with water causing reduction in the surface tension
in the local region. Owing to the higher surface tension of water in th
e neighbor, water is pulled from the alcohol dropped region into the
neighbor, and this leads to the formation of a dry spot in the middle
of the water layer.
 Compressed tablet manufacture
• The classification of manufacturing methods

wet granulation: suitable for drugs that are stable to

granulation moisture and heat
dry granulation: suitable for drugs that are sensitive to
moisture and heat
powder compression : suitable for drugs that are sensitive
direct to moisture and heat, fill material possessing, good
compression flowability and compressibility
crystal compression ： suitable for drugs with
proper crystal form and good flowability
 wet granulation

drug adhesive

smash sieving mix prilling

excipients

lubricant
processing press
dry mix
granule
 dry granulation

adhesive
drug
press processing
smash sieving mix smash
cake granule
excipient

mix press
 powder compression

adhesive
drugs
mix press
smash sieving mix
excipients
 • crystal compression

drugs adhesive
smash sieving

mix mix press

excipients
• wet granulation technology
• ( 一 )wet granulation methods and equipment:

• 1.Extrusion grain methods and equipment: first prescripti

on drug powder and the auxiliary materials mixed evenly
to join adhesive soft material system, then with soft mate
rial compulsory extrusion way through has a certain size
screen hole and granulating method.
wet granulation
 Compressed tablet manufacture
—— wet granulation
• The steps of wet granulation
weighing and blending the ingredients(disintegrant)
(liquid
binder)
preparing a damp mass Internal( 内加
法)
screening the damp mass into pellets or granules

drying the granulation

sizing the granulation by dry screening External( 外加

法)

adding lubricant and disintegrant, and blending

tableting by compression
 The classification of tablet presses
• Tablet presses:

a. single-punch presses
b. multi-station rotary presses
The main components of single-punch t
ablet presses
t a b l e t
h o p p e r

h a r d n e s s

a d j u s t o r

Core components:
f e e d

s h o e

die d i e

u p p e r

c a v i t y

lower punch p u n c h

upper punch d i e

l o w e r

p u n c h

t a b l e t e j e c t o r

a d j u s t o r

t a b l e t w e i g h t

a d j u s t o r
The basic mechanical process of tableting w
ith single-punch presses
a) filling material
u p p e r

a ) b ) c )

p u n c h

b) scraping away the excessive gra t a b l e t

nulation
c) forming a tablet by compression
f i l l

m a t e r i a l

d) pushing up the tablet to stage su l

p
o

u
w

n
e

c
r

h
d i e

rface d ) e ) a

e) shoving the tablet aside

A picture of multi-station rotary press

hopper
feed-frame
head: upper turret, lower turret, die table

upper turret
die table
lower turret
 The core components and compression cycl
e of rotary presses

A: upper punch
B: die cavity
C: die
D: lower punch

The compression
is applied by both
the upper punch
and the lower
punch.
The compression cycle of a rotary tablet press
 Compressed tablet manufacture
—— Direct compression tableting

Suitable for
1) granular chemicals possessing free flowing and cohesiv
e properties
e.g. potassium chloride
2) chemicals added with special pharmaceutical excipient
s which impart the necessary qualities for the production
of tablets by direct compression
The direct compression tableting excipients include:

a) fillers, as spray-dried lactose, microcrystals of alphamonohydrate la

ctose, sucroseinvert ,sugar – corn starch mixtures, microcrystalline
cellulose, crystalline malt and dicalcium phosphate;

d) disintegrants, as direct-compression starch, sodium carboxymethyl

starch, cross-linked carboxymethylcellulose fiber, and cross-linked p
olyvinylpyrrolidone;

c) lubricants, as magnesium stearate and talc;

d) glidants, fumed silicon dioxide

• Sophora Alopecuruldes L ． Seed Tablet o
ptimization
 excipient

prilling 、
powder of sophora processing mix
AIopecuroides L ． Seed
mix 制软材
granule

press

1 ％ Magnesium
stearate
 table 1 the influence of different adhesive to Tablet hardness

formula 1 2 3 4

adhesive 10% 10%PVP 10%CMC-Na 10%PVP

Starch （ water ） (Ethanol)
Hardness 0.68 0.83 0.75 particles
（ Kg ） deformed
table 2 the influence of different fillers to Tablet hardness

formula 5 6 7 8

fillers starch Pregelati lactose 10%PVP

( Ethanol)
nized
starch
Hardnes 0.68 0.77 3.14 3.55
s （ Kg
）
 table 3 factor level
Factor level
A [The amount of 80 120 160
Microcrstalline cellulose(g)]

A [Concentration of PVP 10 15 20
solution （ % ， g/ml)]
 table 4 Result of Orthogonal test
A×B Result
Total
Test NO. 　　 A 　　 B Ⅰ Ⅱ
1 2

1 1 1 1 1
2 1 2 2 2 3.1 2.9 6.0
3 1 3 3 3 2.8 3.1 5.9
4 2 1 2 3 3.2 2.7 5.9
5 2 2 3 1 4.1 4.4 8.5
6 2 3 1 2 4.0 4.1 8.1
7 3 1 3 2 4.2 3.4 8.5
8 3 2 1 3 4.0 3.8 7.8
9 3 3 2 1 3.9 4.2 8.1
K1 17.8 23.0 21.4 22.2
K2 24.2 21.8 22.5 22.0
K3 24.4 21.6 22.5 22.2

1.1 0.2
R×6 6.6 1.4 0.6
 table5 Analysis of variance table
variance source SS V MS F P

total variance 5.658

A 4.698 2 2.349 33.562 0.0001

B 0.191 2 0.096 1.366 0.3034

A×B 0.139 4 0.035 0.993 0.4077

error 0.630 9 0.070

table ６　微晶纤维素用量影响苦豆子片硬度的ｑ检验（ｎ＝６）
Comparison 两均数之 value of q Number
group 差 standard error of ｑ界值 P
group α =0.05 α= 0.01

A1andA3 -1.1 0.1074 -10.241 3 4.34 6.33 <0.01

A1andA2 -1.0 0.1074 -9.310 2 3.46 5.24 <0.01

A2andA3 -0.1 0.1074 -9.310 2 3.46 5.24 >0.05

 Tablet coating

The reasons for tablet coating

1) to protect the medicinal agent against destructive exposure to air a
nd/or humidity;
2) to mask the taste of the drug;
3) to provide special characteristics of drug release;
4) to provide aesthetics or distinction to the product;
5) to prevent inadvertent contact by nonpatients with the drug substan
ce
The general methods involved in coating tablets are as follows
1) sugarcoating tablets
2) film-coating tablets
3) enteric coating
4) pan coating
5) fluid-bed or air suspension coating
6) compression coating
The sugarcoating of tablets may be divided into the followin
g steps:
1) waterproofing and sealing (if needed)
2) subcoating
3) smoothing and final rounding
4) finishing and coloring (if desired)
5) polishing
片芯 ——包层隔离——包粉衣层——包糖衣层——包有色糖衣层——打光
film-coating machine
1) waterproofing and sealing (if needed)

aim: to prevent the components from being adversely affe

cted by moisture; one or more coats; shellac , zein , or a
polymer as cellulose acetate phthalate
2) Subcoating aim: to bond the sugar coating to the tablet
and provide rounding
a) 3 to 5 subcoats of a sugar-based syrup are applied. Th
e sucrose and water syrup also contains gelatin, acacia,
or PVP.
b) When the tablets are partially dry they are sprinkled with
a dusting powder, usually a mixture of powdered sugar a
nd starch but sometimes talc, acacia, or precipitated chal
k as well.

c) Then drying the tablets. Repetition (15 to 18 times) the s

ubcoating process until the tablets are of the desired sha
pe and size.
3) smoothing and final rounding
aim: to complete the rounding and smooth the coatings
5 to 10 additional coatings of a thick syrup; This syrup is sucro
se-based with or without additional components as starch a
nd calcium carbonate.
4) finishing and coloring
aim: to attain final smoothness and the appropriate color
several coats of a thin syrup containing the desired colorant
5) imprinting
aim: to impart identification codes and other distinctive symbols to the
product
The imprint may be debossed, embossed, engraved, or printed on the
surface with ink.
6) polishing
aim: to render the tablets the desired sheen/gloss/luster
a) pans lined with canvas cloth impregnated with carnauba waxand/o
r beeswax
b) Pieces of wax may be placed in a polishing pan
c) light-spraying of the tablets with wax dissolved in a nonaqueous so
lvent
 Tablet coating
—— film-coating tablets
1) The disadvantages of sugarcoating process
a) time-consuming
b) requiring the expertise of highly skilled technicians
c) doubling the size and weight of the original uncoated tablets
d) may vary in size from batch to batch and within a batch
e) large tablets are not as easily swallowed as are small tablets.
2) The advantages of film-coating process
a) coated tablets having essentially the same weight, shape, and size
as the originally compressed tablet
b) The coating is thin enough to reveal any identifying monograms.
c) far more resistant to destruction by abrasion than are sugar-coated
tablets
d) the coating may be colored to make the tablets attractive and distin
ctive.
3) The components of nonaqueous film-coating solutions:
a) film former: e.g. CAP
b) alloying substance: to provide water solubility or permeability to th
e film e.g. PEG
c) plasticizer: to render flexibility and elasticity to the coating e.g. ca
stor oil
d) surfactant: to enhance spreadability of the film e.g. polyoxyethyle
ne sorbitan derivatives
e) opaquants and colorants: e.g. titanium dioxide, FD&C or D&C dye
s
f) sweeteners, flavors, and aromas: saccharin, vanillin
g) glossant: beeswax
h) volatile solvent: alcohol-acetone mixture
4) The components of a typical aqueous film-coating solutio
ns:
a) film-forming polymer (7-18%): e.g. cellulose ether poly
mers as HPMC, HPC and MC
b) plasticizer (0.5-2.0%): e.g. glycerin, propylene glycol, P
EG, diethyl phthalate, and dibutyl subacetate
c) colorant and opacifier (2.5-8%): FD&C or D&C lakes an
d iron oxide pigments
d) water
5) Some problems with aqueous film-coating
a) picking and peeling the appearance of small amounts or large am
ounts of film fragments flaking from the tablet surface
b) orange peel effect roughness of the tablet surface due to failure of
spray droplets to coalesce
c) mottling an uneven distribution of color on the tablet surface
d) bridging
filling-in of the score-line or indented logo on the tablet by the film
e) tablet erosion
disfiguration of the core tablet
5) Some problems with aqueous film-coating
a) picking and peeling the appearance of small amounts or large am
ounts of film fragments flaking from the tablet surface
b) orange peel effect roughness of the tablet surface due to failure of
spray droplets to coalesce
c) mottling an uneven distribution of color on the tablet surface
d) bridging
filling-in of the score-line or indented logo on the tablet by the film
e) tablet erosion
disfiguration of the core tablet
The reasons for capping, splittin
g or laminating of tablets
1) air entrapment

2) not immaculately cleaned or not perfectly

smoothed punches
3) too great a proportion of fine powder
4) Tablets have aged or have been stored im
properly
quality standards and compendial r
equirements
The apparent physical features of compressed tablets:
1) shape: round, oblong, unique 2) thickness: thick or thin
3) diameter: large or small 4) flat or convex
5) unscored or scored in halves, thirds and quadrants
6) engraved or imprinted with an identifying symbol and/or code numb
er
7) coated or uncoated 8)colored or uncolored 9) number of layer.

The die and punches determine the physical features of compressed t

ablets.
quality standards and compendial r
equirements
 Other physical specifications and quality standards:

tablet weight weight variation

content uniformity tablet thickness

tablet hardness tablet disintegration

drug dissolution
 in-process controls
 verification after the production
 quality standards and compendial requirements
—— tablet weight and Chp weight variation

 Chp weight variation: sam Average Weight

weight variation
ple amount 20 tablets limit
 Tablets should comply wit
Less than ± 7.5%
h the following requireme 0.3 g
nts stated in the table bel
ow. 0.3 g or ± 5%
more
电子称量仪
 quality standards and compendial requirements
—— tablet weight and Chp weight variation

The procedure of weight variation determination in Chp:

Weigh accurately 20 tablets and calculate the average w
eight, then weigh individually each of the 20 tablets. Com
pare the weight of each tablet with the labelled tablet (if n
o labelled weight is stated, compare the weight of each t
ablet with the average weight calculated). No more than
2 of the individual weights exceed the weight variation li
mit stated in the table above and none doubles the limit.
 quality standards and compendial requirements
—— tablet hardness and friability

Tablet hardness
1)The greater the pressure applied, the harder the tablets.
2) The hardness required by different tablets

a) lozenges and buccal tablets: hard (dissolve slowly)

b) the tablets for immediate drug release: soft
3) measurement

a) special dedicated hardness testers

b) multifunctional equipment
 quality standards and compendial requirements
—— content uniformity

 applys to potent drug of low dose.

 USP method, 10 tablets are individually assayed for their

content.
The amount of active ingredient in each tablet lies within th
e range of 85% to 115% of the label claim and the RSD i
s less than 6.0%.
 quality standards and compendial requirements
—— tablet hardness and friability
(continued)

Friability
1) It is used to determine a tablet’s durability
2) Method: allowing the tablets to roll and fall within the rot
ating apparatus (friabilator); determine the loss in weight;
3) requirement: weight loss ≤1%
硬度检测仪
片剂脆碎度检测仪
溶出仪
自动溶出取样机
 quality standards and compendial requirements
—— tablet dissolution

1) The importance of in vitro dissolution test

a) to guide the formulation and product development proce

ss toward product optimization
b) to monitor the performance of manufacturing process
c) to assure bioequivalence from batch to batch
d) as a requirement for regulatory approval for product mar
keting for products registered with the FDA and regulator
y agencies of other countries.
2) The goal of in vitro dissolution is to provide a re
asonable prediction of the product’s in vivo bioav
ailability.
Basis: The combinations of a drug’s solubility and i
ts intestinal permeability are supposed as a basi
s for predicting the likelihood of achieving a succ
essful in vivo – in vitro correlation (IVIVC).
Considered are drugs determined to have:
a) high solubility and high permeability (IVIVC m
ay be expected.)
b) low solubility and high permeability (IVIVC ma
y be expected.)
c) high solubility and low permeability
d) low solubility and low permeability
3) The formulation and manufacturing factors affec
ting the dissolution of a tablet
a) the particle size of the drug substance
b) the solubility and hygroscopicity of the formulat
ion
c) the type and concentration of the disintegrant,
binder, and lubricant used
d) the manufacturing method, particularly, the co
mpactness of the granulation and the compressi
on force
e) the in-process variables
4) Test method
a) A volume of the dissolution medium is placed in the ves
sel and allowed to come to 37℃±0.5℃.
b) The stirrer is rotate at the specified speed.
c) At stated intervals, samples of the medium are withdraw
n for chemical analysis
5) Requirement for rate of dissolution
The specific required rates of dissolution are different for ta
blets containing different medicinal agents.
e.g. not less than 85% of the labeled amount is dissolved i
n 30 minutes
6) Inconsistencies in dissolution
occur not between dosage units from the same production
batch, but rather between batches or between products f
rom different manufacturers.

Pooled dissolution testing has emerged. This process reco

gnizes the concept of batch characteristics and allows po
oled specimens to be tested.