There is a question: How pKa value helps in selection of Dissolution Media during Formulation & Analytical Development?
For Dissolution, Ionized form of a drug is required to be solubilized & released passively into dissolution medium.
While, For Absorption, only unionized form of drug is important to be absorbed passively through the intestinal membrane.
Therefore there must be a balance between the fraction of drug in ionized and unionized form.
pKa of a drug is the pH at which 50% of the drug exists in its ionized hydrophilic form in equilibrium with its un-ionized lipophilic form.
Thus, from dissolution point of view for the selection of dissolution medium, the pH of dissolution medium should at least one (most preferably two) pH units above (for acidic drugs) or below (for basic drugs) the pKa of the drug on the side of the ionized form of the molecule.
From absorption point of view the weak base is absorbed at a faster rate from the intestine (pH 7.50 – 8), this is because the basic substances can’t be ionized in basic medium. So the uncharged substances can be passed easily due to its lipid solubility.
Similarly, weak acid is absorbed at a faster rate from stomach (pH 1.4 – 2) as it can’t be ionized in acidic medium.
Read also:
- How to Increase Solubility of Drug?
- Pharmaceutical Finished Product Specification and Template
- Design of Experiments (DOE) in Drug Formulation Development
Resource person: Dr. Shivang Chaudhary