Department of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, University, MS 38677, USA; Department of Pharmacy, East Jeddah Hospital, Ministry of Health, Jeddah 22253, Saudi Arabia.
Department of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, University, MS 38677, USA.
Int J Pharm. 2022 Aug 25;624:121951. doi: 10.1016/j.ijpharm.2022.121951. Epub 2022 Jun 23.
Amorphous solid dispersions (ASDs) have gained attention as a formulation strategy in recent years, with the potential to improve the apparent solubility and, hence, the oral bioavailability of poorly soluble drugs. The process of formulating ASDs is commonly faced with challenges owing to the intrinsic physical and chemical instability of the initial amorphous form and the long-term physical stability of drug formulations. Numerous research publications on hot-melt extrusion (HME) technology have demonstrated that it is the most efficient approach for manufacturing reasonably stable ASDs. The HME technique has been established as a faster scale-up production strategy for formulation evaluation and has the potential to minimize the time to market. Thermodynamic evaluation and theoretical predictions of drug-polymer solubility and miscibility may assist to reduce the product development cost by HME. This review article highlights robust and established prediction theories and experimental approaches for the selection of polymeric carriers for the development of hot melt extrusion based stable amorphous solid dispersions (ASDs). In addition, this review makes a significant contribution to the literature as a pilot guide for ASD assessment, as well as to confirm the drug-polymer compatibility and physical stability of HME-based formulations.
无定形固体分散体（ASD）近年来作为一种制剂策略受到关注，有可能提高难溶性药物的表观溶解度，从而提高口服生物利用度。由于初始无定形形式的固有物理和化学不稳定性以及药物制剂的长期物理稳定性，ASD 的配方过程通常面临挑战。大量关于热熔挤出（HME）技术的研究出版物表明，它是制造合理稳定 ASD 的最有效方法。HME 技术已确立为配方评估的更快放大生产策略，并有可能最大限度地缩短上市时间。药物-聚合物溶解度和混溶性的热力学评估和理论预测可能有助于通过 HME 降低产品开发成本。本文综述强调了用于开发基于热熔挤出的稳定无定形固体分散体（ASD）的聚合物载体选择的强大且已建立的预测理论和实验方法。此外，该综述作为 ASD 评估的初步指南，以及确认基于 HME 的制剂的药物-聚合物相容性和物理稳定性，为文献做出了重要贡献。
