A Method to Predict the Equilibrium Solubility of Drugs in Solid Polymers near Room Temperature Using Thermal Analysis

• Published in: Journal of pharmaceutical sciences Vol. 101; no. 12; pp. 4549 - 4558
• Main Authors: Bellantone, Robert A., Patel, Piyush, Sandhu, Harpreet, Choi, Duk Soon, Singhal, Dharmendra, Chokshi, H., Malick, A. Waseem, Shah, Navnit
• Format: Journal Article
• Language: English
• Published: Hoboken Elsevier Inc 01.12.2012; Wiley Subscription Services, Inc., A Wiley Company; Wiley; American Pharmaceutical Association; Elsevier Limited
• Subjects: Acrylates - chemistry; amorphous; Biological and medical sciences; Calorimetry, Differential Scanning; General pharmacology; Griseofulvin - chemistry; Indomethacin - chemistry; Itraconazole - chemistry; Medical sciences; Models, Chemical; Pharmaceutical Preparations - chemistry; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; polymers; Polymers - chemistry; Povidone - chemistry; solid solution; Solubility; Temperature; thermal analysis; Thermodynamics; thermodynamics; amorphous; polymers; solid solution; Solubility; thermal analysis; Drug; Thermodynamics; Temperature; Pharmaceutical technology; Polymer; Thermal analysis; Physicochemical properties; Solution
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1002/jps.23319

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 ΔGSS 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 ΔGSS from thermal analysis data is demonstrated, and it is shown that minima of plots of ΔGSS 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.