Hu Chunhui, Yan Qiuli, Zhang Yong, Yan Haiying
State Key Laboratory of Plateau Ecology and Agriculture, Qinghai University, Xining 810001, China.
Medical College, Qinghai University, Xining 810001, China.
Pharmaceuticals (Basel). 2023 Nov 22;16(12):1640. doi: 10.3390/ph16121640.
This study investigates the influence of humidity on the dissolution behavior and microstructure of drugs in crystalline solid dispersions (CSDs). Using Bifonazole (BFZ) as a model drug, CSDs were prepared through spray drying with carriers such as Poloxamer 188 (P188), Poloxamer 407 (P407), and polyethylene glycol 8000 (PEG8000). The solubilization effect and mechanism were initially evaluated, followed by an examination of the impact of humidity (RH10%) on the dissolution behavior of CSDs. Furthermore, the influence of humidity on the microstructure of CSDs was investigated, and factors affecting the humidity stability of CSDs were summarized. Significant enhancements in the intrinsic dissolution rate (IDR) of BFZ in CSDs were observed due to changes in crystalline size and crystallinity, with the CSD-P188 system exhibiting the best performance. Following humidity treatment, the CSD-P407 system demonstrated the least change in the IDR of BFZ, indicating superior stability. The CSD-P407 system was followed by the CSD-P188 system, with the CSD-PEG8000 system exhibiting the least stability. Further analysis of the microstructure revealed that while humidity had negligible effects on the crystalline size and crystallinity of BFZ in CSDs, it had a significant impact on the distribution of BFZ on the CSD surface. This can be attributed to the water's potent plasticizing effect, which significantly alters the molecular mobility of BFZ. Additionally, the compatibility of the three polymers with BFZ differs, with CSD-P407 > CSD-P188 > CSD-PEG8000. Under the continuous influence of water, stronger compatibility leads to lower molecular mobility and more uniform drug distribution on the CSD surface. Enhancing the compatibility of drugs with polymers can effectively reduce the mobility of BFZ in CSDs, thereby mitigating changes caused by water and ultimately stabilizing the surface composition and dissolution behavior of drugs in CSDs.
本研究考察了湿度对药物在结晶性固体分散体（CSD）中的溶解行为和微观结构的影响。以联苯苄唑（BFZ）为模型药物，通过喷雾干燥法，使用泊洛沙姆188（P188）、泊洛沙姆407（P407）和聚乙二醇8000（PEG8000）等载体制备CSD。首先评估了增溶效果和机制，随后考察了湿度（RH10%）对CSD溶解行为的影响。此外，研究了湿度对CSD微观结构的影响，并总结了影响CSD湿度稳定性的因素。由于晶体尺寸和结晶度的变化，观察到BFZ在CSD中的固有溶解速率（IDR）显著提高，其中CSD-P188系统表现出最佳性能。经过湿度处理后，CSD-P407系统中BFZ的IDR变化最小，表明其稳定性 superior。CSD-P407系统之后是CSD-P188系统，CSD-PEG8000系统稳定性最差。对微观结构的进一步分析表明，虽然湿度对CSD中BFZ的晶体尺寸和结晶度影响可忽略不计，但对BFZ在CSD表面的分布有显著影响。这可归因于水的强增塑作用，它显著改变了BFZ的分子流动性。此外，三种聚合物与BFZ的相容性不同，CSD-P407 > CSD-P188 > CSD-PEG8000。在水的持续影响下，更强的相容性导致更低的分子流动性和CSD表面更均匀的药物分布。提高药物与聚合物的相容性可有效降低BFZ在CSD中的流动性，从而减轻水引起的变化，最终稳定CSD中药物的表面组成和溶解行为。
