Mohammad A Altamimi1,2, Steven H Neau1. 1. a Department of Pharmaceutical Sciences , Philadelphia College of Pharmacy, University of the Sciences , Philadelphia , PA , USA and. 2. b Department of Pharmaceutical Sciences , College of Pharmacy, King Saud University , Riyadh , Kingdom of Saudi Arabia.
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® 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® using a quick technique. Drug melting point depression (MPD) was measured using differential scanning calorimetry. The Flory-Huggins Theory allowed: (1) interaction parameter, χ, 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® 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®. 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® interacts effectively with each drug, making solid solution formation feasible. The predicted solubility of the drugs in Soluplus® compared favorably across the methods and supports the use of the onset of melting.
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® 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® using a quick technique. Drug melting point depression (MPD) was measured using differential scanning calorimetry. The Flory-Huggins Theory allowed: (1) interaction parameter, χ, 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® 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®. 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® interacts effectively with each drug, making solid solution formation feasible. The predicted solubility of the drugs in Soluplus® compared favorably across the methods and supports the use of the onset of melting.
Authors: Sultan M Alshehri; Faiyaz Shakeel; Mohamed A Ibrahim; Ehab M Elzayat; Mohammad Altamimi; Kazi Mohsin; Osaid T Almeanazel; Musaed Alkholief; Abdullah Alshetaili; Bader Alsulays; Fars K Alanazi; Ibrahim A Alsarra Journal: Saudi Pharm J Date: 2018-11-14 Impact factor: 4.330
Authors: Mohammad A Altamimi; Ehab M Elzayat; Wajhul Qamar; Sultan M Alshehri; Abdelrahman Y Sherif; Nazrul Haq; Faiyaz Shakeel Journal: Saudi Pharm J Date: 2019-03-07 Impact factor: 4.330