Groupe de Chimie Analytique de Paris-Sud, Univ Paris-Sud, Châtenay-Malabry, France.
Eur J Pharm Biopharm. 2012 Aug;81(3):657-65. doi: 10.1016/j.ejpb.2012.04.006. Epub 2012 Apr 26.
The dissolution method is still widely used to determine curing end-points to ensure long-term stability of film coatings. Nevertheless, the process of curing has not yet been fully investigated. For the first time, joint techniques were used to elucidate the mechanisms of dynamic curing over time from ethylcellulose (Aquacoat)-based coated tablets. X-ray micro-computed tomography (XμCT), Near Infrared (NIR), and Raman spectroscopies as well as X-ray microdiffraction were employed as non-destructive techniques to perform direct measurements on tablets. All techniques indicated that after a dynamic curing period of 4h, reproducible drug release can be achieved and no changes in the microstructure of the coating were any longer detected. XμCT analysis highlighted the reduced internal porosity, while both NIR and Raman measurements showed that spectral information remained unaltered after further curing. X-ray microdiffraction revealed densification of the coating layer with a decrease in the overall coating thickness of about 10 μm as a result of curing. In addition, coating heterogeneity attributed to cetyl alcohol was observed from microscopic images and Raman analysis. This observation was confirmed by X-ray microdiffraction that showed that crystalline cetyl alcohol melted and spread over the coating surface with curing. Prior to curing, X-ray microdiffraction also revealed the existence of two coating zones differing in crystalline cetyl alcohol and sodium lauryl sulfate concentrations which could be explained by migration of these constituents within the coating layer. Therefore, the use of non-destructive techniques allowed new insights into tablet coating structures and provided precise determination of the curing end-point compared to traditional dissolution testing. This thorough study may open up new possibilities for process and formulation control.
溶解法仍然广泛用于确定固化终点，以确保薄膜涂层的长期稳定性。然而，固化过程尚未得到充分研究。首次采用联合技术，从乙基纤维素（Aquacoat）包衣片中阐明了随时间变化的动态固化机制。X 射线微计算机断层扫描（XμCT）、近红外（NIR）和拉曼光谱以及 X 射线微衍射被用作非破坏性技术，对片剂进行直接测量。所有技术都表明，在 4 小时的动态固化期后，可以实现重现性的药物释放，并且不再检测到涂层的微观结构发生变化。XμCT 分析突出显示内部孔隙率降低，而 NIR 和拉曼测量都表明，进一步固化后光谱信息保持不变。X 射线微衍射显示出涂层层的致密化，由于固化，整体涂层厚度减少了约 10 μm。此外，从微观图像和拉曼分析中观察到归因于鲸蜡醇的涂层不均匀性。X 射线微衍射证实了这一观察结果，表明结晶鲸蜡醇在固化过程中熔化并在涂层表面扩散。在固化之前，X 射线微衍射还揭示了存在两个涂层区域，其结晶鲸蜡醇和十二烷基硫酸钠浓度不同，这可以通过这些成分在涂层内的迁移来解释。因此，与传统的溶解测试相比，非破坏性技术的使用为片剂包衣结构提供了新的见解，并提供了固化终点的精确确定。这项全面的研究可能为工艺和配方控制开辟新的可能性。
