Biorelevant Dissolution Media

Abstract

Oral administration is the most convenient way to deliver drugs, and therefore the most preferred. However, the oral route is very complex based on the phys- iological conditions encountered by the drug as it passes from the mouth to the absorptive sites in the intestine. When moving from the stomach through the pylorus into the small intestine, the drug will meet a rapidly changing envi- ronment including bile and pancreatic secretions which will introduce different enzymes and surface active bile components, and increase in pH from acidic to neutral. Physiological factors such as the rate of gastric emptying, intestinal motility, blood flow, as well as volume, composition and pH of alimentary secre- tions are known to impact the rate and/or extent of drug absorption. The basic parameters determining the absorption of a drug compound after oral admin- istration are its solubility and permeability in the conditions associated with the gastrointestinal (GI) tract. An increasing problem for the pharmaceutical industry, partly arising from the introduction of high throughput screening, is the discovery of highly hy- drophobic active pharmaceutical candidates with low water solubility (Lipinski, 2000). Many ofthese compounds have a high permeability and are consequently classified as Class 2 compounds according to the Biopharmaceutical Classifica- tion System (BCS). The solubilization and/or dissolution in the gastrointesti- nal tract are the rate-limiting steps for the absorption of Class 2 compounds; as a result, classic solid formulations of Class 2 compounds often exhibit low and/or variable oral bioavailability which is highly influenced by the dietary state (fasted/post-prandial).