Use of the Flory Huggins theory to predict the solubility of nifedipine and sulfamethoxazole in the triblock, graft copolymer Soluplus
Abstract Context: Drug dispersed in a polymer can improve bioavailability; dispersed amorphous drug undergoes recrystallization. Solid solutions eliminate amorphous regions, but require a measure of the solubility. Objective: Use the Flory Huggins Theory to predict crystalline drugs solubility in the triblock, graft copolymer Soluplus(r) to provide a solid solution. Materials and methods: Physical mixtures of the two drugs with similar melting points but different glass forming ability, sulfamethoxazole and nifedipine, were prepared with Soluplus(r) using a quick technique. Drug melting point depression (MPD) was measured using differential scanning calorimetry. The Flory Huggins Theory allowed: (1) interaction parameter, kh, calculation using MPD data to provide a measure of drug polymer interaction strength and (2) estimation of the free energy of mixing. A phase diagram was constructed with the MPD data and glass transition temperature (Tg) curves. Results: The interaction parameters with Soluplus(r) and the free energy of mixing were estimated. Drug solubility was calculated by the intersection of solubility equations and that of MPD and Tg curves in the phase diagram. Discussion: Negative interaction parameters indicated strong drug polymer interactions. The phase diagram and solubility equations provided comparable solubility estimates for each drug in Soluplus(r) Results using the onset of melting rather than the end of melting support the use of the onset of melting. Conclusion: The Flory Huggins Theory indicates that Soluplus(r) interacts effectively with each drug, making solid solution formation feasible. The predicted solubility of the drugs in Soluplus(r) compared favorably across the methods and supports the use of the onset of melting.
Drug development and industrial pharmacy