Factors Affecting Dissolution: Drug Permeability, Stability and Stereochemistry

Most orally administered drugs travel through the GI tract and diffuse passively through intestinal membranes to enter the systemic circulation.

The amount of drug absorbed depends on effective membrane permeability, available surface area for absorption, apparent luminal drug concentration, and residence time in the lumen.

Among these factors, enhancing drug permeability by adjusting lipophilicity, polarity, or molecular size boosts its passive transport across intestinal membranes.

Stability can significantly impact a drug's bioavailability. Degradation during shelf life or conversion by the GI components renders drugs inactive or poorly soluble, diminishing absorption. 

For instance, erythromycin rapidly degrades in an acidic stomach. An enteric coating stabilizes its tablets, enhancing bioavailability.

Many drugs are available as a mixture of enantiomers with different spatial configurations. While stereoisomers influence carrier-mediated absorption, stereoselectivity does not impact passive absorption.

In addition, stereoselectivity does play a role in protein binding.