Qiang Wei, Löbmann Korbinian, McCoy Colin P, Andrews Gavin P, Zhao Min
School of Pharmacy, Queen's University Belfast, Belfast BT9 7BL, UK.
Department of Pharmacy, University of Copenhagen, 2100 Copenhagen, Denmark.
Pharmaceutics. 2020 Jul 11;12(7):655. doi: 10.3390/pharmaceutics12070655.
The thermodynamically unstable nature of amorphous drugs has led to a persistent stability issue of amorphous solid dispersions (ASDs). Lately, microwave-induced in situ amorphization has been proposed as a promising solution to this problem, where the originally loaded crystalline drug is in situ amorphized within the final dosage form using a household microwave oven prior to oral administration. In addition to circumventing issues with physical stability, it can also simplify the problematic downstream processing of ASDs. In this review paper, we address the significance of exploring and developing this novel technology with an emphasis on systemically reviewing the currently available literature in this pharmaceutical arena and highlighting the underlying mechanisms involved in inducing in situ amorphization. Specifically, in order to achieve a high drug amorphicity, formulations should be composed of drugs with high solubility in polymers, as well as polymers with high hygroscopicity and good post-plasticized flexibility of chains. Furthermore, high microwave energy input is considered to be a desirable factor. Lastly, this review discusses challenges in the development of this technology including chemical stability, selection criteria for excipients and the dissolution performance of the microwave-induced ASDs.
无定形药物的热力学不稳定性质导致了无定形固体分散体（ASDs）持续存在的稳定性问题。最近，微波诱导原位非晶化被提出作为解决这一问题的一种有前景的方法，即在口服给药前，使用家用微波炉在最终剂型中将最初负载的结晶药物原位非晶化。除了规避物理稳定性问题外，它还可以简化ASDs有问题的下游加工过程。在这篇综述文章中，我们阐述了探索和开发这项新技术的重要性，重点是系统地综述该制药领域目前可用的文献，并突出诱导原位非晶化所涉及的潜在机制。具体而言，为了实现高药物非晶性，制剂应包含在聚合物中具有高溶解度的药物，以及具有高吸湿性和良好链后增塑柔韧性的聚合物。此外，高微波能量输入被认为是一个理想因素。最后，本综述讨论了该技术开发中的挑战，包括化学稳定性、辅料选择标准以及微波诱导ASDs的溶解性能。
