Quantitative Approach to Factors Influencing Solubility of Drugs

A Quantitative Approach to Factors Influencing Solubility of Drugs solubility involves analyzing how physicochemical properties and environmental conditions affect dissolution.

Key Factors Influencing Solubility:

1. Physicochemical Properties:

   1. Molecular Size and Structure: Larger molecules typically have lower solubility.
   2. Polarity and pKa: Polar drugs and ionized forms are more soluble in water; the Henderson-Hasselbalch equation determines ionization.
   3. Partition Coefficient (Log P): Indicates lipophilicity; higher log P means higher solubility in lipophilic solvents.

2. Environmental Factors Influencing Solubility of Drugs:

   1. Temperature: Solubility generally increases with temperature (van’t Hoff equation).
   2. Solvent Properties: High dielectric constant solvents (e.g., water) dissolve polar substances better.
   3. pH: Affects drug ionization and solubility; buffering maintains pH stability.

3. Formulation Factors:

   1. Particle Size: Smaller particles dissolve faster (Noyes-Whitney equation).
   2. Solid State Forms: Amorphous forms are more soluble than crystalline ones.
   3. Additives and Excipients: Surfactants, cyclodextrins, and co-solvents enhance solubility.

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