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抗逆转录病毒药物的多态性和共结晶的回顾

Retrospection on polymorphism and cocrystallization of anti-retrovirals.

机构信息

University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh-160014, India.

出版信息

Curr Top Med Chem. 2013 Aug;13(16):1933-62. doi: 10.2174/15680266113139990129.

Abstract

Successful pharmaceutical development of a drug molecule depends not only on its potency and selectivity but also on its solid state. Thus the properties of active pharmaceutical ingrdient depend on the identity of its constituents as well as on their arrangement. It is quite common for a drug molecule to exist in more than one crystalline arrangement leading to polymorphism. The various polymorphs differ from each other in dissolution rate, bioavailability, oral absorption, toxicology and clinical trial results. Ultimately both safety and efficacy are impacted by properties that vary among different solid forms. In the recent years screening of polymorphs is increasingly emphasised in the pharmaceutical industry not only because of the valuable knowledge obtained provides necessary guidance for further development but also because of the issue of intellectual property rights. Cocrystallization is an emerging area of research and provides a unique opportunity to enhance marketed products or to pursue compounds that had otherwise been deemed non developable. This review discusses that how common polymorphism among anti- retroviral and its effect on their efficacy. Prevalence of cocrystallization in improving the bioavailability and efficacy of these pharmaceutically important drugs is also incorporated.

摘要

药物分子的成功制药开发不仅取决于其效力和选择性,还取决于其固态。因此,活性药物成分的性质不仅取决于其成分的身份,还取决于它们的排列方式。药物分子通常存在于不止一种晶体排列方式中,从而导致多态性。各种多晶型物在溶解速率、生物利用度、口服吸收、毒理学和临床试验结果方面存在差异。最终,不同固体形式之间的差异会影响安全性和疗效。近年来,制药行业越来越强调多晶型的筛选,不仅因为获得的有价值的知识为进一步开发提供了必要的指导,还因为知识产权问题。共结晶是一个新兴的研究领域,为增强已上市产品或开发以前被认为不可开发的化合物提供了独特的机会。本文综述了抗逆转录病毒药物中常见的多晶型现象及其对疗效的影响。还讨论了共结晶在提高这些具有重要药用价值的药物的生物利用度和疗效方面的应用。

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