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Preformulation 120318030500 Phpapp02
Preformulation 120318030500 Phpapp02
ON
PHARMACEUTICAL FACTORS
AFFECTING DOSAGE FORM
(PREFORMULATION)
1
INTRODUCTION
DEFINITION:
Characterization of physical, chemical and mechanical properties of new drug
molecule in order to develop safe, effective, and stable dosage form.
GOAL OF PREFORMULATION:
To formulate an elegant, safe, efficacious dosage form with good
bioavailability.
To formulate new dosage form of already existing drug.
Determination of all the properties of drug and the best suitable dosage form
for the drug molecule.
2
PHARMACEUTICAL FACTORS
AFFECTING DOSAGE FORMS
Pharmaceutical factor mainly include those parameters of drug which affect the
final dosage form manufacturing process like…..
Flow property
Density
Compressibility
Hygroscopicity
Electrostatic charge
Osmolarity
Rheology
Wettability
Syringabilty
3
1) FLOW PROPERTY
(A) Introduction
Flow property is an important factor that determines the fate of drug
molecule.
Sufficient flow is required for uniformity of dosage form. So it is necessary
to judge the flow of material in preformulation stage of the dosage form.
However extreme increase in flow may improve weight uniformity but may
reduce content uniformity through increased segregation.
REPOSOGRAPH:
5
NEW MEASUREMENT SYSTEM TO EVALUATE
POWDER FLOWABILITY BASED ON VIBRATIONAL
CAPILLARY METHOD:
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Angle of Repose
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DETERMINATION OF
ANGLE OF REPOSE
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RELATION BETWEEN ANGLE OF REPOSE & TYPE
OF FLOW & TYPE OF POWDER
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HAUSNER’S RATIO
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(C) FACTOR AFFECTING FLOW PROPERTY
Hygroscopicity
Electrostatic charge
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(D) IMPROVEMENT OF FLOWABILITY
By addition of glidant
By addition of fine or by size reduction
By wet granulation
By removing static charge
By densification with the help of slugging
Using auger feed equipment
By addition of flow activator. Eg. MgO
By use silicon treated powder for Hygroscopic & moist powder. e.g.
silicon coated talc or Na-bicarbonate
By altering process condition like vibration assisted hopper or forced feeder
By use of spray drying : Advantose 100 maltose powder has improved flow
property than MCC by using this process.
12
2. DENSITY
(A) INTRODUCTION :
The ratio of mass to volume is known as density.
Density = Mass (gms.)/ Volume (ml.)
TYPES OF DENSITY :
(a) Bulk density
(b)Tapped density
(c)True density
(d)Granule density :- may affect compressibility, tablet porosity,
disintegration, dissolution
13
(B) Method of Determination
Parameter Method
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Bulk density measurement :
15
Measurement of True Density:
16
An improved method for fast online measuring of density of
solid substances:
17
(C) CORRELATION WITH FLOWABILITY
(D) IMPORTANCE
In case of combination therapy or physical mixture ,if both drug or drug &
excipients have different density then creates problem of segregation (demixing).
Important in decide size & type of processing equipment. E.g. decide size of
capsule formulation, Suppositories.
Devereux et.al. compared GI transit time of multiple unit formulation of
densities 2.8g/cm3 & 1.5g/cm3 & found significantly delayed gastric emptying
of heavier pdt.
(Review article, IJPS, sept-oct,2008)
18
3. COMPRESSIBILITY
(A) INTRODUCTION
1. PLASTICITY
Plastic material are capable of permanent deformation, also exhibit a
degree of brittleness (fragmentability)
But plastic material will get bonding after Viscoelastic deformation.
2. FRAGMENTABILITY
If material is fragmentable, neither lubricant mixing time nor dwell time
affecting the tablet strength.
(A) INTRODUCTION
Hygroscopicity: - It is the tendency of material to absorb moisture from
atmosphere & be dynamic equilibrium with water in the atmosphere.
Deliquescent: - It is the hygroscopic substance which absorb moisture
from air and they can be liquefied by partially or wholly forming
solution.
Efflorescent: - a substance which loses water to form a lower hydrate or
become anhydrous is term as efflorescent.
“ The length of stick slip event increases with moisture content, increasing
load, etc .”
(Chemical Abstract vol.146:9803)
A) INTRODUCTION:
Electrostatic charges are the consequence of classic attraction &
repulsion effect between the charges.
Electrostatic charge is produced:
By separation of positive & negative charge
By mechanical impact
By friction between two surface
By rupturing of particle
By separation of solid & liquid surface
Effect of moisture.
In preformulation of suspension .
Affects flow property of powder.
Affects mixing process.
For thermal stability of emulsions.
It may damage tablet machine.
It may affect compression coating.
A) INTRODUCTION
It is a colligative property
DEFINITIONS:
Osmoles : No. of osmotically active particles in solution.
Osmolarity : osmoles or milliosmoles per liter of solution.
Osmolality :osmoles or milliosmoles per kg of solvent.
Isoosmotic: when two different solutions are separated by semipermiable
membrane have same osmotic pressure so called as isoosmotic.
Isotonic: when two different solutions are separated by biological
membrane have same osmotic pressure so called as isotonic.
(A) DEFINITION
It describes flow of liquid and/or deformation of solid under stress.
It is a flow in which a direct proportionality exists between shear stress and shear
rate. E.g. water, simple organic liquid & dilute suspension , Glycerin.
Where there no direct relation between shear stress and shear rate.
Capillary viscometer
Falling sphere viscometer
Cup and bob viscometer
Cone and plate viscometer
Brook field viscometer
Ultrasonic Shear Rheometer :- For analysing protein solution rheology.
Instron Capillary Rheometer :- Measures viscosity as a function of rate of shear
& temp at a high rate of shear.
[1] FLUID
For mixing
For particle size reduction of disperse system
Passing though orifice, pouring, packaging in bottle,
passing though hypodermic needle.
Flow though pipe
Physical stability of disperse system
[2] QUASISOLIDS
Spreading and adherence to skin
Removal from jar
Capacity of solids to mix with liquid
Release of drug fromANAND
basePHARMACY COLLEGE, ANAND 44
[3] SOLID
Flow of powder from hopper and into a die cavity in tableting or in
encapsulation
Packagability of powder or granules solids.
[4] PROCESSING
Production capacity of the equipment
Processing efficiency
THIXOTROPHY:
In thixotropy apply shear stress convert gel – sol & remove shear stress convert
sol – gel, means gel to sol to gel.
Application :- for stability of suspension
e.g. conc. Parental suspension containing 40-70% w/v of procaine penicillin G
(A) INTRODUCTION
By contact angle:
The contact angle is the angle between a liquid droplet and the surface over
which it spreads.
Contact angle – 00 – complete wetting.
Contact angle – 1800 – No wetting .
By Draves test:
(C) IMPORTANCE:
Crystal structure can influence the contact angle.
Problems associated with Wettability of powder are poor dissolution rate &
low adhesion of film coating.
Use of wetting agent (HLB value 6-9) which acts by lowering contact
angle. It displaces air & replace it with liquid phase.
Alfred Martin, physical Pharmacy, 4thedition, 1999, B.I. Waverly, New Delhi.
Leon Lachman ,H.A. Lieberman , J.L.Kanig , the theory and practice of
industrial pharmacy ,2nd edition
Leon Lachman, H, A. Lieberman, Pharmaceutical dosage form –tablet volume
1
Leon Lachman, H, A. Lieberman, Pharmaceutical dosage form-parental
Dosage form volume 1
Michael E. Aulton, Pharmaceutics: The science of dosage form design ELBS
publication
Remington, the science and practice of pharmacy, 21st Edition
Encyclopedia of pharmaceutical technology vol. 14 Marcel Decker