Institute of Biopharmaceutical Research, Liaocheng University, Hunan Road, Liaocheng, Shandong 252059, People's Republic of China.
Institute of Biopharmaceutical Research, Liaocheng University, Hunan Road, Liaocheng, Shandong 252059, People's Republic of China.
Carbohydr Polym. 2021 Dec 1;273:118562. doi: 10.1016/j.carbpol.2021.118562. Epub 2021 Aug 18.
Amorphous solid dispersions (ASDs) are regarded as one of the most promising techniques for poorly-soluble active pharmaceutical ingredients (API). However, the thermodynamic instability of ASDs at supersaturated state makes them easy to recrystallize in aqueous media. In this study, ritonavir (RTV) was selected as a model drug for evaluating the solubility enhancement and recrystallization inhibition effect of various cellulose derivatives and the combinations of them with typical surfactants. Combination of HPMCAS-HF/SLS was filtrated for preparing ternary RTV solid dispersions (RTV SD) via solvent evaporation method. RTV SD exhibited enhanced dissolution manner, while the oral bioavailability of RTV SD was equivalent with the Reference Standard Norvir® but increased significantly compared to the ternary physical mixture. Thus, the ternary SD system might be promisingly employed as efficient drug delivery system for RTV, while the HPMCAS-HF/SLS combination could be recommended as effective excipient for fabricating steady solid dispersions loading poorly soluble API.
无定形固体分散体（ASD）被认为是提高难溶性活性药物成分（API）溶解度的最有前途的技术之一。然而，ASD 在过饱和状态下的热力学不稳定性使得它们在水介质中容易重结晶。在这项研究中，利托那韦（RTV）被选为模型药物，用于评估各种纤维素衍生物及其与典型表面活性剂组合的增溶和抑制重结晶效果。通过溶剂蒸发法，将 HPMCAS-HF/SLS 的组合过滤用于制备三元 RTV 固体分散体（RTV SD）。RTV SD 表现出增强的溶解方式，而 RTV SD 的口服生物利用度与参比标准 Norvir®相当，但与三元物理混合物相比显著增加。因此，三元 SD 系统有望作为 RTV 的有效药物传递系统，而 HPMCAS-HF/SLS 组合可作为制备负载难溶性 API 的稳定固体分散体的有效赋形剂。
