(421c) Area 15B/PD2M Plenary Award: Biorelevant Phase Transformations in Supersaturated Solutions of Poorly Water Soluble Drugs

For oral delivery, a drug must first dissolve in the intestinal fluids, and then be absorbed across the gastrointestinal membrane. Unfortunately, many new drugs are poorly soluble in water and are consequently difficult to deliver to the patient.To improve this situation, drugs can be formulated as supersaturating delivery systems such as an amorphous drug-polymer blends or other metastable solid forms. Such systems generate a supersaturated solution in vivo, improving membrane transport rate and ultimately absorption relative to stable crystal forms. However, supersaturated solutions are meta- or unstable and phase transformation to a lower energy state(s) is thermodynamically favored. Such phase transformations include liquid liquid phase separation and crystallization. The nature of the phase transformation and the characteristics of any precipitate formed is important since these can impact the supersaturation profile and the redissolution kinetics of the phase separated material. Herein, different phase transformations and their potential implications for the oral delivery of poorly water soluble drugs are considered.