pKa (Ionization Constant):
Definition:
The pH at which 50% of the drug exists in its ionized form and 50% in its unionized form.
Importance:
Ionized drugs are more soluble in water, while unionized drugs have higher membrane permeability.
Helps predict solubility and absorption in various pH conditions of the gastrointestinal tract.
Example:
A drug with a pKa of 4 will be more ionized at pH below 4 (acidic medium) and unionized at pH above 4 (basic medium).
pH and Solubility Profile:
Definition:
The solubility of a drug is influenced by the pH of the medium.
Importance:
Determines whether the drug dissolves efficiently in physiological fluids.
Helps in selecting buffer systems or pH adjustments to improve solubility.
Example:
Weakly acidic drugs dissolve better in basic pH, while weakly basic drugs dissolve better in acidic pH.
Partition Coefficient (Log P):
Definition:
The ratio of a drug's solubility in oil (lipophilic phase) to water (hydrophilic phase).Expressed as Log P:
Importance:
Determines lipophilicity, which affects membrane permeability and bioavailability.
Low Log P (<1): Highly water-soluble but poorly absorbed.
High Log P (>3): Poorly water-soluble but membrane permeable.
Example:
Drugs with moderate Log P (1–3) show balanced solubility and permeability for oral absorption.