Preformulation Parameters pKa and Solubility

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Preformulation ParameterspKa and Solubility

• PREPARED BY
• VAISHNANI BHAVIN
• M.PHARMA-I
• (Q.A.)

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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

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Definition of pKa and Ka

• Ka is H B-/HB,
  where B is the conjugate base of the
  acid HB
• pKa -Log10 (Ka)

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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.

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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

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DETERMINATION OF pKa

• Henderson-Hesselbalch equations
• UV-VIS. Spectra
• Potentiometric titration
• Solubility measurements
• HPLC techniques
• Capillary zone electrophoresis
• Foaming activity

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Typical titration curves
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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 25C

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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.

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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
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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

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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) Bentleys 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

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