Preformulation Parameters pKa and Solubility

Preformulation ParameterspKa and Solubility

PREPARED BYVAISHNANI

BHAVINM.PHARMA-I(Q.A.)

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

Definition of pKa and Ka

Ka is : [H +] [B-]/[HB], where B is the conjugate base of the acid HB

pKa = -Log10 (Ka)

GI absorbtion of weakly acidic or basic is dependent on many factors like

1. Unionized form

2. pH at the site of absorption,

3. pKa,

4. lipid solubility of the unionized species.

Henderson-Hesselbalch equations:

For acidic comp.pH = pKa + log [ionized drug]

[un-ionized drug]

For basic comp.pH = pKa - log [ionized drug]

[un-ionized drug]

DETERMINATION OF pKaHenderson-Hesselbalch equationsUV-VIS. Spectra Potentiometric titrationSolubility measurementsHPLC techniquesCapillary zone electrophoresisFoaming activity

Typical titration curves ;

SolubilityDefination:

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

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.

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

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

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