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口服药物共晶/有机盐的渗透性研究视角

A Perspective on the Permeability of Cocrystals/Organic Salts of Oral Drugs.

机构信息

Department of Medicinal Chemistry, School of Pharmacy and Targeted Drug Delivery Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad 9177948954, Iran.

出版信息

Mol Pharm. 2024 Oct 7;21(10):4860-4911. doi: 10.1021/acs.molpharmaceut.4c00786. Epub 2024 Sep 16.

Abstract

According to the BCS classification system, the differentiation of drugs is based on two essential parameters of solubility and permeability, meaning the latter is as pivotal as the former in creating marketable pharmaceutical products. Nevertheless, the indispensable role of permeability in pharmaceutical cocrystal profiles has not been sufficiently cherished, which can be most probably attributed to two principal reasons. First, responsibility may be on more user-friendly measurement procedures for solubility compared to permeability, implying the permeability measurement process seems unexpectedly difficult for researchers, whereas they have a complete understanding of solubility concepts and experiments. Besides, it may be ascribed to the undeniable attraction of introducing new crystal-based structures which mostly leaves the importance of improving the function of existing multicomponents behind. Bringing in new crystalline entities, to rephrase it, researchers have a fairly better chance of achieving high-class publications. Although the Food and Drug Administration (FDA) has provided a golden opportunity for pharmaceutical cocrystals to straightforwardly enter the market by simply considering them as derivatives of the existing active pharmaceutical ingredients, inattention to assessing and scaling up permeability which is intimately linked with solubility has resulted in limited numbers of them in the global pharmaceutical market. Casting a glance at the future, it is apprehended that further development in the field of permeability of pharmaceutical cocrystals and organic salts requires a meticulous perception of achievements to date and potentials to come. Thence, this perspective scrutinizes the pathway of permeation assessment making researchers confront their fear upfront through mapping the simplest way of permeability measurement for multicomponents of oral drugs.

摘要

根据 BCS 分类系统,药物的分类基于两个基本参数:溶解度和渗透性,这意味着后者与前者一样,是创造有市场价值的药物产品的关键。然而,渗透性在药物共晶形态中的不可或缺作用并没有得到充分的重视,这可能主要归因于两个主要原因。首先,与渗透性相比,溶解度的测量程序可能更便于用户使用,这意味着渗透性测量过程对研究人员来说似乎出乎意料地困难,而他们对溶解度的概念和实验有全面的了解。此外,这可能归因于引入新的基于晶体的结构的不可否认的吸引力,这主要将改善现有多组分功能的重要性抛在后面。换句话说,引入新的晶体实体,研究人员有更高的机会获得高质量的出版物。尽管食品和药物管理局(FDA)为药物共晶直接进入市场提供了一个绝佳的机会,只需将其视为现有活性药物成分的衍生物即可,但对与溶解度密切相关的渗透性的评估和放大重视不够,导致它们在全球药物市场中的数量有限。展望未来,可以理解,药物共晶和有机盐渗透性领域的进一步发展需要对迄今为止的成就和未来的潜力有细致的认识。因此,这一观点审视了渗透评估的途径,通过为口服药物的多组分绘制最简单的渗透性测量方法,让研究人员直面恐惧。

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