A method to predict the equilibrium solubility of drugs in solid polymers near room temperature using thermal analysis

A method is presented for determining the equilibrium solubility of a drug in a solid polymer at or near room temperature, which represents a typical storage temperature. The method is based on a thermodynamic model to calculate the Gibbs energy change ?GSS associated with forming a binary drugpolymer solid solution from the unmixed polymer and solid drug. The model includes contributions from heat capacity differences between the solid solution and the corresponding unmixed components, breaking up of the solid drug structure, and drugpolymer mixing. Calculation of ?GSS from thermal analysis data is demonstrated, and it is shown that minima of plots of ?GSS versus the dissolved drug concentration represent the equilibrium drug solubility in the polymer. Solid solutions were produced for drugpolymer systems (griseofulvin, indomethacin, itraconazole; PVP K30, Eudragit L100, Eudragit E100) in drug weight fractions up to similar to 25%. At 25 degrees C, it was seen that heat capacity effects were important in determining the drug solubility. It was concluded that drug solubilities in solid polymers can be determined using thermal analysis, and must include heat capacity effects when evaluated near room temperature. (c) 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:45494558, 2012