1. Preformulation Parameters pKa and Solubility
PREPARED BY VAISHNANI BHAVIN M.PHARMA-I (Q.A.)

2. Ionization Constant (pKa)
The Ka value is a value used to describe the tendency of compounds or ions to dissociate and is also called the dissociation constant, the ionisation constant and the acid constant.
The pKa value is a value related to the Ka value in a log manner

3. Definition of pKa and Ka
Ka is : [H +] [B-]/[HB], where B is the conjugate base of the acid HB
pKa = -Log10 (Ka)

4. GI absorbtion of weakly acidic or basic is dependent on many factors like
Unionized form
pH at the site of absorption,
pKa,
lipid solubility of the unionized species.

5. Henderson-Hesselbalch equations:
For acidic comp.
pH = pKa + log [ionized drug]
[un-ionized drug]
For basic comp.
pH = pKa - log [ionized drug]

6. DETERMINATION OF pKa Henderson-Hesselbalch equations UV-VIS. Spectra
Potentiometric titration
Solubility measurements
HPLC techniques
Capillary zone electrophoresis
Foaming activity

7. Typical titration curves ;

8. Solubility
Defination:
mass of solute that dissolves in a specific mass or volume of solvent at a given temperature.
eg. 1 gm. Of NaCl dissolves in 2.786ml of water at 25°C

9. Solubility-pH profile
plot of the solubility of the drug at various physiologic pH values.
Solubility may be improved with the addition of an acidic or basic excipient.
eg. Solubilization of aspirin may be increased by addition of an alkaline buffer.

10. Descriptive Term
Parts of Solvent Required for 1 Part of Solute
Very soluble
Less than 1
Freely soluble
From 1 to 10
Soluble
From 10 to 30
Sparingly soluble
From 30 to 100
Slightly soluble
From 100 to 1,000
Very slightly soluble
From 1,000 to 10,000
Practically insoluble or insoluble
10,000 and over

11. General methods of increasing the solubility are:
addition of co-solvent.
eg. Water, alcohol, glycerin
addition of complexing agent
eg. Caffeine, EDTA
Chemical modification of the drug
pH adjustment
addition of surfactant.
eg. Span, tween, SLS

12. Referance (1) Pharmaceutical Preformulation And Formulation
A Practical Guide from Candidate Drug Selection to Commercial Dosage Form
Editor Mark Gibson
Page no. 28,29
(2) Bentley’s Textbook of Pharmaceutics
By E. A. Rawlins
Page No. 19,20
(3) The science of Dosage Form Design, 2nd edition,
Edited by M. E. Aulton,
Page No. 115,116,117,118

13. THANK YOU