Drug-Polymer Solubility and Miscibility: Stability Consideration and Practical Challenges in Amorphous Solid Dispersion Development

Drug polymer solid dispersion has been demonstrated as a feasible approach to formulate poorly water-soluble drugs in the amorphous form, for the enhancement of dissolution rate and bioperformance. The solubility (for crystalline drug) and miscibility (for amorphous drug) in the polymer are directly related to the stabilization of amorphous drug against crystallization. Therefore, it is important for pharmaceutical scientists to rationally assess solubility and miscibility in order to select the optimal formulation (e.g., polymer type, drug loading, etc.) and recommend storage conditions, with respect to maximizing the physical stability. This commentary attempts to discuss the concepts and implications of the drug polymer solubility and miscibility on the stabilization of solid dispersions, review recent literatures, and propose some practical strategies for the evaluation and development of such systems utilizing a working diagram. (C) 2010 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:2941-2947, 2010