Molecular Profiles Ltd, 8 Orchard Place, Nottingham Business Park, Nottingham NG8 6PX, UK.
Int J Pharm. 2011 Jul 29;414(1-2):210-7. doi: 10.1016/j.ijpharm.2011.05.037. Epub 2011 May 20.
Nanothermal analysis (NTA) supported by atomic force microscopy imaging has been used to study the changes that occur at the surfaces of solid dispersions of the drug felodipine and the water soluble polymer, polyvinylpyrrolidone (PVP) on exposure to standard pharmaceutical environmental stress conditions. Exposure to relative humidities above 75% (at 40 °C) was sufficient to achieve phase separation of the drug and polymer into areas which displayed a glass transition temperature consistent with pure drug and polymer over a period of a few days. Higher values of humidity at 25 °C (e.g. 95%RH) were also sufficient to cause such phase separation within a day. Extended studies of up to two months showed an eventual crystallization of the drug. NTA is shown to be effective at the early detection of instabilities in solid dispersions and the quantifiable identification of the relative composition of phase separated domains based upon their glass transition temperatures. The combined nanoscale analytical approach employed here is able to systematically study the influence of storage conditions and different drug loadings and to evaluate physical stability as a function of environmental conditions.
基于原子力显微镜成像的纳米热分析（NTA）已被用于研究在暴露于标准药物环境应激条件下，药物非洛地平的固体分散体与水溶性聚合物聚乙烯吡咯烷酮（PVP）表面发生的变化。在相对湿度高于 75%（40°C）的条件下暴露足够长的时间，药物和聚合物会发生相分离，形成的区域显示出与纯药物和聚合物一致的玻璃化转变温度，这一过程只需几天时间。在 25°C 时（例如 95%RH）湿度更高也足以在一天内引起这种相分离。长达两个月的扩展研究表明，药物最终会结晶。NTA 可有效早期检测固体分散体的不稳定性，并根据其玻璃化转变温度对相分离区域的相对组成进行定量识别。这里采用的组合纳米尺度分析方法能够系统地研究储存条件和不同药物负载的影响，并评估物理稳定性与环境条件的关系。
