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共结晶:调控活性药物成分物理化学性质的尖端工具。

Cocrystallization: Cutting Edge Tool for Physicochemical Modulation of Active Pharmaceutical Ingredients.

机构信息

Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi - 835215, Jharkhand, India.

出版信息

Curr Pharm Des. 2020;26(38):4858-4882. doi: 10.2174/1381612826666200720114638.

Abstract

Cocrystallization is a widely accepted and clinically relevant technique that has prospered very well over the past decades to potentially modify the physicochemical properties of existing active pharmaceutic ingredients (APIs) without compromising their therapeutic benefits. Over time, it has become an integral part of the pre-formulation stage of drug development because of its ability to yield cocrystals with improved properties in a way that other traditional methods cannot easily achieve. Cocrystals are solid crystalline materials composed of two or more than two molecules which are non-covalently bonded in the same crystal lattice. Due to the continuous efforts of pharmaceutical scientists and crystal engineers, today cocrystals have emerged as a cutting edge tool to modulate poor physicochemical properties of APIs such as solubility, permeability, bioavailability, improving poor mechanical properties and taste masking. The success of cocrystals can be traced back by looking at the number of products that are getting regulatory approval. At present, many cocrystals have obtained regulatory approval and they successfully made into the market place followed by a fair number of cocrystals that are currently in the clinical phases. Considering all these facts about cocrystals, the formulation scientists have been inspired to undertake more relevant research to extract out maximum benefits. Here in this review cocrystallization technique will be discussed in detail with respect to its background, different synthesis approaches, synthesis mechanism, application and improvements in drug delivery systems and its regulatory perspective.

摘要

共晶结晶是一种被广泛接受且与临床相关的技术,在过去几十年中得到了蓬勃发展,有望改变现有活性药物成分 (API) 的物理化学性质,而不会损害其治疗效果。随着时间的推移,它已成为药物开发前配方阶段的一个组成部分,因为它能够以其他传统方法不易实现的方式生成具有改善性能的共晶。共晶是由两个或两个以上分子通过非共价键结合在同一晶格中的固态结晶材料。由于制药科学家和晶体工程师的不断努力,共晶现在已成为一种前沿工具,可以调节 API 的物理化学性质,如溶解度、渗透性、生物利用度,改善较差的机械性能和掩盖不良味道。通过查看获得监管批准的产品数量,可以追溯共晶的成功。目前,许多共晶已获得监管批准并成功推向市场,随后还有相当数量的共晶目前处于临床阶段。考虑到共晶的所有这些事实,制剂科学家受到启发进行更多相关研究以提取最大的效益。在这篇综述中,将详细讨论共晶结晶技术,包括其背景、不同的合成方法、合成机制、在药物传递系统中的应用和改进及其监管视角。

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