Department of Pharmaceutical Sciences, School of Food and Biological Engineering, Shaanxi University of Science and Technology, Weiyang University Park, Xi'an 710021, People's Republic of China.
Department of Pharmaceutics, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang 110016, People's Republic of China.
Int J Pharm. 2020 Apr 30;580:119240. doi: 10.1016/j.ijpharm.2020.119240. Epub 2020 Mar 17.
Multiple carriers may be used to prepare solid dispersions (SDs) for different purposes. The aim of this work is to investigate the effect of the third component on the physical stability and physical aging behavior of cinnarizine-soluplus SDs. HPMC, PVP, sorbitol and citric acid were used as the third component to prepare cinnarizine ternary SDs using hot melt extrusion method. The resultant samples were stored at 25 °C or under stress conditions. Differential scanning calorimetry, powder X-ray diffraction and dissolution tests were performed to investigate the changes of samples during the storage. Infrared spectroscopy was used to evaluate the interactions between drug and carriers. Results showed that the addition of HPMC or PVP enhanced the physical stability of ternary SDs stored at 25 °C rather than those stored under stress conditions. Sorbitol did not show any improvements in physical stability of samples stored at 25 °C or under stress conditions. Surprisingly, the physical stability of samples stored at 25 °C or under stress conditions was enhanced significantly by citric acid due to the ionic and hydrogen bonding interactions. The miscibility between drug and carriers as well as between different carriers should be considered when using multiple carriers. The third component can act as a "linker" by interacting with drug and polymer to enhance the physical stability of SDs effectively.
多种载体可用于制备具有不同用途的固体分散体（SD）。本工作旨在研究第三组分对肉桂嗪-共聚维酮 SD 的物理稳定性和物理老化行为的影响。采用热熔挤出法，以 HPMC、PVP、山梨醇和柠檬酸为第三组分制备肉桂嗪三元 SD。将所得样品在 25℃或应力条件下储存。采用差示扫描量热法、粉末 X 射线衍射和溶出度试验研究样品在储存过程中的变化。采用红外光谱法评价药物与载体之间的相互作用。结果表明，在 25℃储存时，HPMC 或 PVP 的加入增强了三元 SD 的物理稳定性，而在应力条件下储存时则没有增强。山梨醇对在 25℃或应力条件下储存的样品的物理稳定性没有任何改善。令人惊讶的是，柠檬酸通过离子和氢键相互作用，显著增强了在 25℃或应力条件下储存的样品的物理稳定性。在使用多种载体时，应考虑药物和载体之间以及不同载体之间的混溶性。第三组分可以通过与药物和聚合物相互作用作为“连接剂”，有效地增强 SD 的物理稳定性。
