Use of the Flory-Huggins Theory to predict the solubility of nifedipine and sulfamethoxazole in the triblock graft copolymer Soluplus

Journal Article

2015

Ph.D, Mohammad A. Altamimi, . 2015

Purpose: Solid dispersions of crystalline drugs in polymer matrices are promising as an approach to improve bioavailability. However, the high energy of an amorphous drug in a solid dispersion leads to crystallization. In this work, the Flory-Huggins Theory predicts the solubility of crystalline drugs in the triblock graft copolymer Soluplus® to provide a solid solution of molecularly dispersed drug with negligible opportunities for crystallization.
Methods: The melting point depression of each of two BCS II drugs, sulfamethoxazole (SMX) and nifedipine (NIF), was measured at various polymer levels using differential scanning calorimetry to allow calculation of the interaction parameter, c. c provides a measure of drug-polymer interaction strength and allows the estimation of the free energy of mixing the drug with the polymer and, hence, its solubility in that polymer. Drug solubility in the polymer is calculated by solving solubility equations and by construction of a phase diagram.
Results: A negative interaction parameter for SMX and NIF with Soluplus® indicated a relatively strong drug-polymer interaction. The free energy of mixing and the solubility of each drug in Soluplus® were then estimated. The calculated solubility of each drug is in agreement across the two methods.
Conclusion: The Flory-Huggins Theory indicates that Soluplus® interacts effectively with each of the drugs. The predicted solubility of the drugs in Soluplus® compared favorably across the two methods and with literature values. This approach proves to be faster and more efficient than others reported in the literature.