title: A method to predict the equilibrium solubility of drugs in solid polymers near room temperature using thermal analysis.
abstract: 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 ΔG(SS) associated with forming a binary drug-polymer 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 drug-polymer mixing. Calculation of ΔG(SS) from thermal analysis data is demonstrated, and it is shown that minima of plots of ΔG(SS) versus the dissolved drug concentration represent the equilibrium drug solubility in the polymer. Solid solutions were produced for drug-polymer systems (griseofulvin, indomethacin, itraconazole; PVP K30, Eudragit L100, Eudragit E100) in drug weight fractions up to ∼25%. At 25°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.
authors.affiliation: Division of Pharmaceutical Sciences, Arnold & Marie Schwartz College of Pharmacy and Health Sciences, Long Island University, Brooklyn, New York 11201, USA. rbellant@liu.edu
authors.forename: Robert A
authors.initials: RA
authors.lastname: Bellantone
authors.forename: Piyush
authors.initials: P
authors.lastname: Patel
authors.forename: Harpreet
authors.initials: H
authors.lastname: Sandhu
authors.forename: Duk Soon
authors.initials: DS
authors.lastname: Choi
authors.forename: Dharmendra
authors.initials: D
authors.lastname: Singhal
authors.forename: H
authors.initials: H
authors.lastname: Chokshi
authors.forename: A Waseem
authors.initials: AW
authors.lastname: Malick
authors.forename: Navnit
authors.initials: N
authors.lastname: Shah
mesh_terms: D000179:Acrylates / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D006118:Griseofulvin / Q000737:chemistry; D007213:Indomethacin / Q000737:chemistry; D017964:Itraconazole / Q000737:chemistry; D008956:Models, Chemical; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D011205:Povidone / Q000737:chemistry*; D012995:Solubility; D013696:Temperature; D013816:Thermodynamics
chemical_list: D000179:Acrylates; C477020:Eudragit E100; D004364:Pharmaceutical Preparations; D011108:Polymers; D017964:Itraconazole; D006118:Griseofulvin; D011205:Povidone; D007213:Indomethacin