Stabilization of Low Glass Transition Temperature Indomethacin Formulations: Impact of Polymer-Type and Its Concentration

• Published in: Journal of pharmaceutical sciences Vol. 97; no. 6; pp. 2286 - 2298
• Main Authors: Chokshi, Rina J., Shah, Navnit H., Sandhu, Harpreet K., Malick, Ahmad W., Zia, Hossein
• Format: Journal Article
• Language: English
• Published: Hoboken Elsevier Inc 01.06.2008; Wiley Subscription Services, Inc., A Wiley Company; Wiley; American Pharmaceutical Association
• Subjects: Anti-Inflammatory Agents, Non-Steroidal - chemistry; Biological and medical sciences; Calorimetry, Differential Scanning; Chemistry, Pharmaceutical; crystallinity; Crystallography, X-Ray; dissolution rate; Drug Compounding; Drug Stability; extrusion; General pharmacology; glass transition; Indomethacin - chemistry; Kinetics; Medical sciences; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; polymers; Povidone - chemistry; Powder Diffraction; Pyrrolidines - chemistry; solid dispersion; solid solutions; Solubility; Spectroscopy, Fourier Transform Infrared; stability; Technology, Pharmaceutical - methods; thermal analysis; Transition Temperature; Vinyl Compounds - chemistry; X-ray powder diffractometry; dissolution rate; solid dispersion; extrusion; X-ray powder diffractometry; crystallinity; solid solutions; polymers; glass transition; stability; thermal analysis; Prostaglandin-endoperoxide synthase; Stabilization; Indometacin; Solid dispersion; Powder; Tocolytic; Glass transition; Formulation; Indoleacetic acid derivatives; Solution; Stability; Pharmaceutical technology; Enzyme; Enzyme inhibitor; Polymer; Concentration; Crystallinity; Dissolution; Glass transition temperature; Non steroidal antiinflammatory agent; Extrusion; Oxidoreductases; Thermal analysis; X ray diffractometry; Physicochemical properties
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1002/jps.21174

The objectives of this study were to formulate and stabilize amorphous formulation of low Tg drug (Indomethacin, INM) with selected polymers and compare these formulations based on solubility and dissolution rate studies. Eudragit EPO (EPO), Polyvinylpyrrolidone–vinyl acetate copolymer (PVP–VA), and Polyvinylpyrrolidone K30 (PVPK30) were selected as hydrophilic polymers. The melt extrudates were characterized using differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), intrinsic dissolution rate and solubility studies. The formation of single-phase amorphous form was confirmed by DSC and PXRD. The melt extrudates showed a higher intrinsic dissolution rate (IDR), and solubility compared to the pure drug. The amorphous drug in solid solutions with EPO, PVP–VA, and PVPK30 showed tendency to revert back to crystalline form. However, the rate of reversion was dependent on the nature and concentration of the polymer. The solid solution with high ratio of EPO provided superior stabilization of the amorphous INM from crystallization. The stability of the amorphous form of INM could not be related to the glass transition temperature of the formulation as the mechanism of stabilization with EPO appears to be molecular interaction rather than immobilization. The presence of specific molecular interactions between INM and EPO was also shown by the antiplasticization effect.