ABSTRACT
The physiological environment at the site of drug administration and the drug physicochemical properties are important factors in determining the rate and extent of drug absorption after extravascular drug administration. The drugs have to be in solution before diffusing across the biological membrane and reaching the systemic circulation. Different drugs have different dissolution rates and different abilities to cross biological membranes, which lead to different absorption characteristics. Hydrophilic drugs, in general, have faster rate of dissolution in the aqueous physiological environment and lower diffusivity through the lipophilic biological
membranes, whereas lipophilic drugs have lower aqueous solubility and higher membrane diffusivity. Since most drugs are either weak acids or weak bases, the drug solubility is usually affected by the pH of the surrounding environment. Basic drugs can dissolve faster and are mostly ionized in the acidic pH of the stomach, while their dissolution is slower and are mostly unionized in the alkaline pH of the small intestine. The reverse can be observed for acidic drugs: slower dissolution and mostly unionized in the stomach, whilst faster dissolution and mostly ionized in the small intestine. All properties that can affect drug solubility, dissolution rate, stability, and diffusivity across the biological membrane under the physiological conditions can affect the rate and extent of drug absorption. These include the molecular structure features that can affect the drug physicochemical properties as well as the drug properties in the bulk powder form.
