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治疗性深共晶溶剂:它们的热力学、微观结构和药物传递应用的综合评述。

Therapeutic deep eutectic solvents: A comprehensive review of their thermodynamics, microstructure and drug delivery applications.

机构信息

Pharmaceutical Engineering Group, School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast BT9 7BL, UK; Pharmaceutical Technology Department, Faculty of Pharmacy, Tanta University, Tanat, Egypt.

Pharmaceutical Engineering Group, School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast BT9 7BL, UK.

出版信息

Eur J Pharm Biopharm. 2023 May;186:85-104. doi: 10.1016/j.ejpb.2023.03.002. Epub 2023 Mar 11.


DOI:10.1016/j.ejpb.2023.03.002
PMID:36907368
Abstract

Deep eutectic solvents (DES) are multicomponent liquids that are usually formed by coupling a hydrogen bond donor and acceptor leading to strong non-covalent (NC) intermolecular networking and profound depression in the melting point of the system. Pharmaceutically, this phenomenon has been exploited to improve drugs' physicochemical properties, with an established DES therapeutic subcategory, therapeutic deep eutectic solvents (THEDES). THEDES preparation is usually via straightforward synthetic processes with little involvement of sophisticated techniques, which, in addition to its thermodynamic stability, make these multi-component molecular adducts a very attractive alternative for drug enabling purposes. Other NC bonded binary systems (e.g., co-crystals and ionic liquids) are utilized in the pharmaceutical field for enhancing drug's behaviours. However, a clear distinction between these systems and THEDES is scarcely discussed in the current literature. Accordingly, this review provides a structure-based categorization for DES formers, a discussion of its thermodynamic properties and phase behaviour, and it clarifies the physicochemical and microstructure boundaries between DES and other NC systems. Additionally, a summary of its preparation techniques and their experimental conditions preparation is supplied. Instrumental analysis techniques can be used to characterize and differentiate DES from other NC mixtures, hence this review draws a road map to for this purpose. Since this work mainly focuses on pharmaceutical applications of DES, all types of THEDES including the highly discussed types (conventional, drugs dissolved in DES and polymer based) in addition to the less discussed categories are covered. Finally, the regulatory status of THEDES was investigated despite the current unclear situation.

摘要

深共熔溶剂 (DES) 是由氢键供体和受体耦合而成的多组分液体,通常形成强非共价 (NC) 分子间网络,导致体系熔点显著降低。在药学中,这种现象已被用于改善药物的物理化学性质,形成了一个已确立的 DES 治疗亚类,即治疗深共熔溶剂 (THEDES)。THEDES 的制备通常通过简单的合成工艺进行,很少涉及复杂的技术,除了其热力学稳定性外,这些多组分分子加合物作为药物赋形剂非常有吸引力。其他 NC 键合二元体系(例如共晶和离子液体)也在制药领域用于增强药物的行为。然而,目前的文献中几乎没有讨论这些体系与 THEDES 之间的明显区别。因此,本综述提供了 DES 形成剂的基于结构的分类,讨论了其热力学性质和相行为,并阐明了 DES 与其他 NC 体系之间的物理化学和微观结构边界。此外,还提供了其制备技术及其实验条件的摘要。仪器分析技术可用于表征和区分 DES 与其他 NC 混合物,因此,本综述为此目的绘制了路线图。由于这项工作主要集中在 DES 的药物应用上,因此涵盖了所有类型的 THEDES,包括高度讨论的类型(常规、溶解在 DES 中的药物和基于聚合物的)以及讨论较少的类别。最后,尽管目前情况尚不清楚,但仍调查了 THEDES 的监管状况。

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