Miscibility/stability considerations in binary solid dispersion systems composed of functional excipients towards the design of multi-component amorphous systems

The correlations between amorphous miscibility/physical stability of binary solid dispersions (a highly crystalline additive-an amorphous polymer) and the physicochemical properties of the components were investigated. Crystalline functional excipients including surfactants, organic acids, and organic bases were prepared in binary solid dispersions in amorphous polymers by solvent evaporation method. Amorphous miscibility and physical stability of the systems were characterized using polarized light microscope, differential scanning calorimeter, and powder X-ray diffraction. Physicochemical parameters (solubility parameter (δ), hydrogen bond energy, Log P, pKa value as an indicator of acid-base ionic interaction, and Tg of the dispersion as a surrogate of system's mobility) were selected as thermodynamic and kinetic factors to examine their influences on the systems' amorphous miscibility and physical stability. All systems possessing acid-base ionic interaction formed amorphous state. In the absence of the ionic interaction, solubility parameter and partition coefficient were shown to have major roles on amorphous formation. Upon storage condition at 25°C/60% RH for 50 days, systems having ionic interaction and high Tg remained in the amorphous state. This binary system study provides an insight and a basis for formation of the amorphous state of multi-component solid dispersions utilizing their physicochemical properties. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:4711-4723, 2009