Use of the Flory-Huggins theory to predict the solubility of nifedipine and sulfamethoxazole in the triblock, graft copolymer Soluplus.
BACKGROUND
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.


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.


CONCLUSIONS
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.


CONCLUSIONS
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.
a Department of Pharmaceutical Sciences , Philadelphia College of Pharmacy, University of the Sciences , Philadelphia , PA , USA and.|b Department of Pharmaceutical Sciences , College of Pharmacy, King Saud University , Riyadh , Kingdom of Saudi Arabia.
Mohammad A
MA
Altamimi
a Department of Pharmaceutical Sciences , Philadelphia College of Pharmacy, University of the Sciences , Philadelphia , PA , USA and.
Steven H
SH
Neau
D005544:Forecasting; D009543:Nifedipine / Q000737:chemistry* / Q000493:pharmacokinetics; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000493:pharmacokinetics; D011145:Polyvinyls / Q000737:chemistry* / Q000493:pharmacokinetics; D012995:Solubility; D013420:Sulfamethoxazole / Q000737:chemistry* / Q000493:pharmacokinetics; D013816:Thermodynamics
D011145:Polyvinyls; C572167:polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer; D011092:Polyethylene Glycols; D009543:Nifedipine; D013420:Sulfamethoxazole
Melting point depression; miscibility; phase diagram; solid dispersion; solid solution