Factors Influencing Drug Absorption: Physicochemical Parameters

The physicochemical properties of drugs are essential parameters for designing stable and bioavailable drug products.

A drug's solubility depends on the varying pH along the GI tract and its dissociation constant, or pKa. The pKa determines its ionization state and absorption rate. As weak acids and bases remain unionized, they are absorbed more rapidly.

Reduced particle sizes and larger surface areas enhance the drug's interaction with bodily fluids. This accelerates dissolution and subsequently augments absorption.

Some drugs are not chemically stable in the stomach's acidic environment. So, coating the tablet with an acid-resistant film or enteric coating mostly resists degradation until it reaches the small intestine, where absorption occurs.

Lipophilic drugs with high partition coefficients can pass through cell membranes for absorption despite poor aqueous solubility.

Drugs can exhibit many structural forms, such as amorphous, polymorphs, and solvates. Due to their higher energy state, amorphous forms,  dissolve more rapidly than crystals, promoting drug absorption.