1. Physicochemical
properties of drug
substances.
- Vishnu Datta.M

2. Physicochemical properties of drug
substances
•
•
•
•
•
•
•
•
•
Drug solubility and dissolution rate
Particle size and effective surface area
Polymorphism and Amorphism
Pseudo polymorphism (hydrates/solvates)
Drug stability
Salt form of the drug
Lipophilicity of the drug
pka of the drug and gastrointestinal pH
Stereochemical nature of the drug

3. Particle size &
Effective surface area

4. Particle size &
Effective surface area
• Particle size and surface area of a solid
drug are inversely related.
• Two types of surface area of interest are:
 Absolute surface area
 Effective surface area

5. Particle size &
Effective surface area
• Absolute surface area which is the total area
of solid surface of any particle.
• Effective surface area which is the area of
solid surface exposed to the dissolution
medium.

6. Particle size &
Effective surface area

7. Particle size &
Effective surface area
• Micronisation>>>reduction of particle size
• Surface of such small particles has higher
energy than the bulk of the solid
>>>increased interaction with the solvent

8. Particle size &
Effective surface area
• In case of non hydrophobic
drugs(griseofulvin, chloramphenicol, salts of
tetracycline) >>>micronisation>>>superior
dissolution rate in comparison to the simple
milled form of these drugs.
>>>decreased dose >>>increased absorption
efficiency
• Ex: Griseofulvin reduced to half and
Spironolactone decreased 20 times

9. Particle size &
Effective surface area
• In case of hydrophobic drugs (aspirin,
phenacetin, phenobarbital)>>>decrease in
effective surface area of such
powders>>>fall in the dissolution rate.

10. Reasons suggested for the
outcome
• The hydrophobic surface of the drug
adsorbs air onto their surface which inhibits
wettability.
• The particles re-aggregate to form larger
particles due to their high surface free
energy which either float on the surface or
settle at the bottom of dissolution medium

11. Overcome the effects to increase
the effective surface area
• Use of surfactant as a wetting agent
Decreases the interfacial tension
Displaces the adsorbed air with the solvent
Ex: polysorbate 80 increases the bioavailability
of phenacetin by promoting wettability
• Adding hydrophilic diluents such as PEG,
PVP, Dextrose etc which coat the surface of
hydrophobic drug particles and render them
hydrophilic. …

12. Physicochemical properties of drug
substances
•
•
•
•
•
•
•
•
•
Drug solubility and dissolution rate
Particle size and effective surface area
Polymorphism and Amorphism
Pseudo polymorphism (hydrates/solvates)
Drug stability
Salt form of the drug
Lipophilicity of the drug
pka of the drug and gastrointestinal pH
Stereochemical nature of the drug

13. Polymorphism
• Depending on the internal structure a solid
can exist either in a crystalline or
amorphous.
• When a substance exists in more than one
crystalline form, the different forms are
designated as polymorphs and the
phenomenon as polymorphism .

15. Polymorphism
• Polymorphs are two types
Enantiotropic polymorph is the one which
can be reversibly changed into another
form by altering the temperature or
pressure.ex:sulphur
Monotropic polymorph is the one which is
unstable at all temperatures and
pressures eg:glyceryl stearates.

16. Polymorphism
• Polymorphs differs in physical properties
>>> solubility, Melting point, density,
hardness and compression characteristics
• The existence of the polymorphs can be
determined by using techniques
like>>>optical crystallography, x-ray
diffraction, differential scanning
calorimetry etc.

17. Polymorphism
• Among the polymorphic forms>>>stable
form>>>lowest energy>>>highest melting
point>>>least aqueous solubility
• Remaining polymorphs are called
metastable forms which represent>>>higher
energy state>>>lower melting
point>>>higher aqueous solubility

18. Polymorphism
• As the metastable forms have greater
solubility they show better availability and
are preferred in formulation
• Ex chloramphenicol palmitate A,B,C,D
B shows best bioavailability
A is virtually inactive biologically

19. Amorphous form
• Drugs also exist as amorphous form
>>>have greater aqueous solubility than
the crystalline forms>>>energy required to
transfer a molecule from lattice is greater
than that required for amorphous
• Ex: cortisone acetate is 3 times more
soluble than crystalline form
• Order of dissolution is
Amorphous>metastable>stable

20. Physicochemical properties of drug
substances
•
•
•
•
•
•
•
•
•
Drug solubility and dissolution rate
Particle size and effective surface area
Polymorphism and Amorphism
Pseudo polymorphism (hydrates/solvates)
Drug stability
Salt form of the drug
Lipophilicity of the drug
pka of the drug and gastrointestinal pH
Stereochemical nature of the drug

21. Pseudopolymorphism
 When the solvent molecules are
incorporated in the crystal lattice of the
solid are called as the solvates
 The solvates can exist in different
crystalline form called as
pseudopolymorphs. The phenomenon is
called pseudopolymorphism.

22. Hydrates and Solvates
• If case Entrapped Solvent is water then it is
referred as Hydrate.
• Anhydrous form of the drug has greater aqueous
solubility then the hydrates. (because already in
interaction with water have less energy for
crystal break up in comparison to the
anhydrates).
• Solvates differ in their physical parameters.

23. Physicochemical properties of drug
substances
•
•
•
•
•
•
•
•
•
Drug solubility and dissolution rate
Particle size and effective surface area
Polymorphism and Amorphism
Pseudo polymorphism (hydrates/solvates)
Drug stability
Salt form of the drug
Lipophilicity of the drug
pka of the drug and gastrointestinal pH
Stereochemical nature of the drug

24. Drug stability
• A drug for oral use may destabilize either
during its shelf-life or in the GIT
• Major stability problems resulting in poor
bioavailability of an orally administered drug
Degradation of drug into inactive form
Interaction with one or more different
component(s) to form a complex that is
poorly soluble or is unabsorbable

25. ~~REFERENCES~~
• Physical pharmacy, fourth edition,
Alfred martin.
• Pharmaceutics The science of dosage form
design 2nd edition- M.E Aulton
• Dissolution, Bioavailability & Bioequivalence
Hamed M.Abdou
• Brahmankar D.M., Biopharmaceutics &
pharmacokinetics A Treatise
• Biopharmaceutics and clinical
pharmacokinetics an introducion fourth
edition Robert E.Notari

26. ~~THANK YOU~~
• Knowledge of what is does not open the door directly to what
should be……….
» Albert Einstein