Influence of Glass Forming Ability on the Physical Stability of Supersaturated Amorphous Solid Dispersions |
| |
Authors: | Lasse Ingerslev Blaabjerg Bulut Bulduk Eleanor Lindenberg Korbinian Löbmann Thomas Rades Holger Grohganz |
| |
Institution: | 1. Department of Pharmacy, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark;2. Idorsia Pharmaceuticals Ltd, Hegenheimermattweg 91, CH-4123 Allschwil, Switzerland |
| |
Abstract: | In this study, the influence of the glass-forming ability (GFA) of a drug on its physical stability in a supersaturated solid dispersion was investigated. Nine drugs were classified according to their GFA using their respective critical cooling rate. Their respective solubility in poly(vinylpyrrolidone-co-vinyl acetate) 6:4 (PVPVA64) was predicted using the melting point depression method based on the Flory-Huggins lattice theory. Supersaturated amorphous solid dispersions at a level of 25% w/w drug above saturation solubility in the polymer were prepared by film-casting, and their respective physical stability at temperatures of 10°C or 20°C above or below their respective Tg (dry conditions) was monitored by the use of polarized light microscopy. This study showed that drugs with good GFA (class 3) on average have higher physical stability in supersaturated amorphous solid dispersion compared to drug with modest GFA (class 2), which in turn have higher physical stability in supersaturated amorphous solid dispersion than drugs with poor GFA (class 1). These results indicate that the GFA of a drug and its physical stability in a supersaturated amorphous solid dispersion stored at a temperature above or below its Tg are correlated. |
| |
Keywords: | solubility glass crystallization amorphous physical stability solid state solid dispersion formulation |
本文献已被 ScienceDirect 等数据库收录! |