Counter-intuitive discovery in the formulation of poorly water-soluble drugs: Amorphous small-molecule gels

IF 10.9 1区医学 Q1 CHEMISTRY, MEDICINAL Medicinal Research Reviews Pub Date : 2024-05-28 DOI:10.1002/med.22060

Yecheng Shu, Peixu Zhao, Xin Li, Xianbao Shi, Qiang Fu

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Abstract

Amorphous strategies have been extensively used in improving the dissolution of insoluble drugs for decades due to their high free energy. However, the formation of amorphous small-molecule gels (ASMGs) presents a counter-intuitive discovery that significantly limits their practical application. Recently, ASMGs have garnered attention because of their noncovalent structures, excellent biodegradability, and significant potential in various drug delivery systems in the pharmaceutical field. Hence, a comprehensive review is necessary to contribute to a better understanding of recent advances in ASMGs. This review aimed to introduce the main formation mechanisms, summarize possible influencing factors, generalize unique properties, outline elimination strategies, and discuss clinical application potential with preclinical cases of ASMGs. Moreover, few ASMGs are advanced to clinical stages. Intensive clinical research is needed for further development. We hope that this review can provide more efficient and rational guidance for exploring further clinical applications of ASMGs.

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弱水溶性药物制剂中的反直觉发现：无定形小分子凝胶。

几十年来，无定形策略因其自由能高而被广泛用于改善不溶性药物的溶解。然而，无定形小分子凝胶（ASMGs）的形成是一个反直觉的发现，极大地限制了其实际应用。近来，无定形小分子凝胶因其非共价结构、优异的生物降解性以及在制药领域各种给药系统中的巨大潜力而备受关注。因此，有必要对 ASMG 进行全面综述，以便更好地了解 ASMG 的最新进展。本综述旨在介绍 ASMG 的主要形成机制，总结可能的影响因素，归纳其独特性质，概述消除策略，并结合临床前案例讨论其临床应用潜力。此外，很少有 ASMG 进入临床阶段。要想进一步发展，还需要进行深入的临床研究。我们希望本综述能为探索 ASMGs 的进一步临床应用提供更有效、更合理的指导。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Medicinal Research Reviews 医学-药学

CiteScore

29.30

自引率

0.00%

发文量

审稿时长

2 months

期刊介绍： Medicinal Research Reviews is dedicated to publishing timely and critical reviews, as well as opinion-based articles, covering a broad spectrum of topics related to medicinal research. These contributions are authored by individuals who have made significant advancements in the field. Encompassing a wide range of subjects, suitable topics include, but are not limited to, the underlying pathophysiology of crucial diseases and disease vectors, therapeutic approaches for diverse medical conditions, properties of molecular targets for therapeutic agents, innovative methodologies facilitating therapy discovery, genomics and proteomics, structure-activity correlations of drug series, development of new imaging and diagnostic tools, drug metabolism, drug delivery, and comprehensive examinations of the chemical, pharmacological, pharmacokinetic, pharmacodynamic, and clinical characteristics of significant drugs.

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