Dissolution testing for poorly soluble drugs: A continuing perspective

Abstract

The development of a meaningful dissolution procedure for drug products with limited water solubility has been a challenge to both the pharmaceutical industry and the agencies that regulate them. These challenges include developing and validating the test methods, ensuring that methods are appropriately discriminatory, and addressing the potential for an in vivo-in vitro correlation (IVIVC). Dissolution test media selection should be justified for pH (recommended pH range is 1.2-7.5) as well as surfactant type (ionic versus non-ionic) and amount. If the drug is not soluble in the in vivo pH range, with or without surfactants, then the use of nonaqueous media can be preferred with proper justifications. Physical modifications of the drug, such as particle size reduction, use of metastable polymorphs, eutectic mixtures, solid dispersions, or complexation, are being widely used in the industry to enhance the drug dissolution characteristics. In recent years, newer physical modifications (e.g., microemulsions and nanocrystals) are giving promising results in enhancement of drug dissolution and bioavailability of poorly soluble drugs. Whatever method is used by the dissolution scientists, it must aim towards the cheaper but most effective approach to enhance the dissolution behavior of poorly soluble drugs.