• The solubility profile helps determine how a drug dissolves in bodily fluids, influencing its absorption and bioavailability.
  • pKa, pH, and Log P are key parameters that affect a compound’s solubility profile and its formulation.

pKa (Ionization Constant):

  1. Definition:

    • The pH at which 50
  2. 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.
  3. 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:

  1. Definition:

    • The solubility of a drug is influenced by the pH of the medium.
  2. Importance:

    • Determines whether the drug dissolves efficiently in physiological fluids.
    • Helps in selecting buffer systems or pH adjustments to improve solubility.
  3. Example:

    • Weakly acidic drugs dissolve better in basic pH, while weakly basic drugs dissolve better in acidic pH.

Partition Coefficient (Log P):

  1. Definition:

    • The ratio of a drug’s solubility in oil (lipophilic phase) to water (hydrophilic phase).
    • Expressed as Log P:
    • $\log P = \log \left( \frac{\text{Concentration in octanol}}{\text{Concentration in water}} \right)$
  2. 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.
  3. Example:

    • Drugs with moderate Log P (1–3) show balanced solubility and permeability for oral absorption.

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