Moffat Jonathan G, Qi Sheng, Craig Duncan Q M
School of Pharmacy, University of East Anglia, Norwich, UK, NR4 7TJ.
Pharm Res. 2014 Jul;31(7):1744-52. doi: 10.1007/s11095-013-1279-x. Epub 2014 Feb 20.
In this study we explore the use of nano-scale localized thermal analysis (LTA) and transition temperature microcopy (TTM) as a novel combined approach to studying phase separation in HME dispersions of cyclosporine A in Eudragit EPO.
Modulated temperature differential scanning calorimetry (MTDSC), attenuated total reflectance FTIR spectroscopy, nano-LTA and TTM were performed on raw materials and dispersions prepared by hot melt extrusion (HME) and spin coating. For samples prepared by HME, two mixing temperatures (110°C and 150°C) and residence times (5 and 15 min) were investigated.
Spin coated samples showed an intermediate T g for the mixed systems consistent with molecular dispersion formation. The HME samples prepared at 110°C showed evidence of inhomogeneity using MTDSC and FTIR, while those produced at 150°C h showed evidence for the formation of a single phase system using MTDSC. The nanothermal methods, however, indicated the presence of phase separated cyclosporine A at the higher preparation temperature while the TTM was able to map regions of differing penetration temperatures, indicating the presence of compositionally inhomogeneous regions in all but the high processing temperature/high residence time samples.
TTM is a potentially important new method for studying phase separation and that such separation may remain undetected or poorly understood using conventional bulk analytical techniques.
在本研究中，我们探索使用纳米级局部热分析（LTA）和转变温度显微镜（TTM）作为一种新型组合方法，来研究环孢素A在Eudragit EPO中的热熔挤出（HME）分散体中的相分离。
对通过热熔挤出（HME）和旋涂制备的原材料及分散体进行调制温度差示扫描量热法（MTDSC）、衰减全反射傅里叶变换红外光谱法、纳米LTA和TTM分析。对于通过HME制备的样品，研究了两种混合温度（110°C和150°C）及停留时间（5分钟和15分钟）。
旋涂样品显示混合体系的玻璃化转变温度（Tg）处于中间值，这与分子分散体的形成一致。在110°C制备的HME样品通过MTDSC和FTIR显示出不均匀性的迹象，而在150°C制备的样品通过MTDSC显示出形成单相体系的迹象。然而，纳米热分析方法表明在较高制备温度下存在相分离的环孢素A，而TTM能够绘制不同渗透温度的区域，表明除了高加工温度/高停留时间的样品外，所有样品中均存在成分不均匀区域。
TTM是研究相分离的一种潜在重要新方法，并且使用传统的整体分析技术可能无法检测到这种相分离或对其理解不足。
