Kushwah Varun, Succhielli Cecilia, Saraf Isha, Paudel Amrit
Research Center Pharmaceutical Engineering GmbH, 8010 Graz, Austria.
Institute of Pharmaceutical Science, Department of Pharmaceutical Technology, University of Graz, 8010 Graz, Austria.
Pharmaceutics. 2024 Aug 2;16(8):1035. doi: 10.3390/pharmaceutics16081035.
The present study investigated the effect of different polymers and manufacturing methods (hot melt extrusion, HME, and spray drying, SD) on the solid state, stability and pharmaceutical performance of amorphous solid dispersions. In the present manuscript, a combination of different binary amorphous solid dispersions containing 20% and 30% of drug loadings were prepared using SD and HME. The developed solid-state properties of the dispersions were evaluated using small- and wide-angle X-ray scattering (WAXS) and modulated differential scanning calorimetry (mDSC). The molecular interaction between the active pharmaceutical ingredients (APIs) and polymers were investigated via infrared (IR) and Raman spectroscopy. The in vitro release profile of the solid dispersions was also evaluated to compare the rate and extend of drug dissolution as a function of method of preparation. Thereafter, the effect of accelerated stability conditions on the physicochemical properties of the solid dispersions were also evaluated. The results demonstrated higher stability of Soluplus (SOL) polymer-based solid dispersions as compared to hydroxypropyl methylcellulose (HPMC)-based solid dispersions. Moreover, the stability of the solid dispersions was found to be higher in the case of API having high glass transition temperature (Tg) and demonstrated higher interaction with the polymeric groups. Interestingly, the stability of the melt-extruded dispersions was found to be slightly higher as compared to the SD formulations. However, the down-processing of melt-extruded strands plays critical role in inducing the API crystal nuclei formation. In summary, the findings strongly indicate that the particulate properties significantly influence the performance of the product.
本研究考察了不同聚合物及制备方法（热熔挤出法，HME；喷雾干燥法，SD）对无定形固体分散体的固态性质、稳定性及药物性能的影响。在本论文中，采用喷雾干燥法和热熔挤出法制备了不同二元无定形固体分散体的组合，药物载量分别为20%和30%。使用小角和广角X射线散射（WAXS）以及调制差示扫描量热法（mDSC）对所制备分散体的固态性质进行了评估。通过红外（IR）光谱和拉曼光谱研究了活性药物成分（API）与聚合物之间的分子相互作用。还评估了固体分散体的体外释放曲线，以比较药物溶解速率和程度与制备方法的关系。此后，还评估了加速稳定性条件对固体分散体物理化学性质的影响。结果表明，与羟丙基甲基纤维素（HPMC）基固体分散体相比，基于Soluplus（SOL）聚合物的固体分散体具有更高的稳定性。此外，对于具有高玻璃化转变温度（Tg）的API，固体分散体的稳定性更高，且与聚合物基团表现出更强的相互作用。有趣的是，发现热熔挤出分散体的稳定性比喷雾干燥制剂略高。然而，热熔挤出条带的后处理在诱导API晶核形成中起关键作用。总之，研究结果有力地表明，颗粒性质对产品性能有显著影响。
