ABSTRACT
Over the past several decades, pharmaceutical scientists and formulators have been confronted with the development of a growing number of poorly water-soluble drug candidates (<10▒mg/L). Approximately 90% of new drug candidates advancing in pharmaceutical development are classified as poorly water-soluble by the Food and Drug Administration bioclassification system (BCS). Often, poorly soluble drugs produce relatively low bioavailability (subtherapeutic levels) in the drug’s native state, thus requiring drug modifications to improve both solubility and subsequent therapeutic effectiveness. The type of modification applied very much depends on the nature of the inherent water insolubility, highly lipophilic (grease balls), or highly crystalline (brick dust). Chapter 18 gives a review of recent technologies and techniques used to overcome low drug solubility and provide improved drug bioavailability with a particular interest to size reduction (nanoparticles), complexation (cyclodextrins), and solid dispersion systems. Because drug modification from its native state is discussed, the stability of these modified forms is paramount and noted within. General methods to provide these stable modified drug forms are discussed. The benefit of this chapter is to provide pharmaceutical formulators of poorly water-soluble drugs with a road map of potential approaches to provide greater product bioavailability and stability as well as a robust process to achieve product commercialization.
