3. INTRODUCTION
‘Preformulation can be defined as investigation of physical and
chemical properties of drug substances alone and when
combined with excipients.’
Preformulation investigation are designed to deliver all
necessary data especially physicochemical, biopharmaceutical
properties of drug substances, excipients and packaging
material.
Solubility, partition coefficient, dissolution rate, polymorphism,
stability are plays important role in preformulation study.
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4. GOALS OF PREFORMULATION
To establish the physico-chemical parameters of new
drug substances.
To establish kinetic rate profile.
To establish compatibility with common excipients.
To choose the correct form of drug substances.
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5. PHYSICAL CHARACTERISTICS
Bulk characteristics
Solid state characteristics
Powder flow properties
Angle of repose- tanθ=h /r
Angle of repose
(degree)
Flow property
25-30 Excellent
31-35 Good
36-40 Fair
41-45 Passable
>45 Poor 5
6. Densities
Compressibility and hauser's ratio
CARR’S INDEX(%) =(TAPPED DENSITY – POURED DENSITY) X 100
TAPPED DENSITY
Compressibility
(%)
Flow character Hausner's ratio
<10 Excellent 1.00-1.11
11-15 Good 1.12-1.18
16-20 Fair 1.19-1.25
21-25 Passable 1.26-1.34
>26 Poor 1.35-1.45
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7. Crystalline
Crystal habit & internal structure of drug can affect bulk & physicochemical property
of molecule.
Polymorphism
It is the ability of the compound to crystallize as more than one distinct crystalline
species with different internal lattice.
Polymorphisms are two types –
1. Enantiotropy
2. Monotropic
Hygroscopicity
Many pharmaceutical materials have tendency to absorb atmospheric moisture they
are called as hygroscopic material and this phenomenon is known as hygroscopicity.
Changes in moisture level can influence-chemical stability,flowability,compatibility.
1. Deliquescent
2. Efflorescent 7
8. 8
Solubility analysis
The solubility of drug is an physicochemical property because it affect
rate of drug release into dissolution medium and therapeutic efficacy of
the pharmaceutical product.
Description Part of solvent required for
1 part of solute
Very soluble <1
Freely soluble From 1-10
Soluble From 10-30
Sparingly soluble From 30-100
Slightly soluble From 100-1000
Very slightly soluble From 1000-10000
Poorly soluble >10000
9. Ionization constant-
Can be calculated by Henderson Hasselbach equation-
For acidic drugs….pH= pKa+ log
For basic drugs….pH= pKa+ log
Partition coefficient-
It is the ratio of unionized drug distributed between organic and aqueous
phase at equilibrium.
P o/w = ( C oil / C water )equilibrim
Dissolution -
The dissolution rate of drug substances is described by Noyes whiteny
equation,
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10. Stability analysis
Solid state stability
Solution state stability
Drug excipient compatibility
Importance of drug exicipient compatibility -
1. Any physical or chemical interaction between drug and excipient
can affect bioavailability and stability of drug.
2. It helps to avoid surprise problems.
3. It bridges drug discovery and drug development.
4. Provide evidence as to how the quality of drug product varies with
time.
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12. REFERENCES
1. The theory & practice of industrial pharmacy by Leon Lachman, Herbert A.
Lieberman, 3rd edition, published by CBS, (2009), page no:- 154-217.
2. Ansel’s pharmaceutical Dosage forms & Drug delivery systems, 8th edition
by Loyd V. Allen, Nicholas G.popovich, Howard C. Ansel, published by
wollers kulwer,(2011),page no:- 185.
3. Textbook of physical pharmaceutics by C.V.S. Subrahmanyam,
published by Vallabh prakashan,(2015) ,page no:- 220.
4. Aulton’s Pharmaceutics the Design And Manufacture Of Medicines,
Michael E. Aulton’s, Kevin M.G.Taylor, Fourth edition,(2013),Page No.
188.
5. Textbook Of Pharmaceutics’, Dr.R.S.Gaud, Dr.P.G.Yeole, Dr.A.V.Yadav,
S.B.Gokhale, Nirali Prakashan, (2012), Page No: 5.1-5.4.
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