用于 BCS II 级和 IV 级的溶解度增强技术系统回顾

Pavankumar Dhoble, Bharat Tekade, Vishal Bodke, Mohan Kale
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摘要

由于药物的溶解度低,制药研究人员在研制可持续的、溶解度更高的药物(BCS 二级)时遇到了巨大困难。约有 40% 的口服剂型因不溶于水而存在配方和开发问题。活性药物的溶解、吸收、分布和排泄速度取决于其溶解度参数。根据药物的溶解度,BCS 分类系统将药物分为四类。BCS 二类和四类药物在溶解度方面存在问题。提高溶解性差的药物的生物利用度和溶解度有多种方法。一些技术,如固体分散技术、固体络合技术、液固技术、水凝技术、声波结晶技术和自乳化技术,通常用于提高药物的溶解度。口服活性药物在溶解于胃黏膜和/或肠液之前,无法通过消化道膜进入血液。因此,不溶于水的药物通常会表现出有限的溶解吸收,而通过膜弱渗透的药物通常会表现出有限的渗透吸收。因此,提高活性物质的口服生物利用度是两个制药研究领域的重点:(i) 加快水溶性差的药物的溶解和溶解过程,(ii) 加快渗透性差的药物的渗透过程。
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A Systematic Review of Solubility Enhancement Techniques Used for BCS Class II & IV
Because of their low solubility, pharmaceutical researchers encounter tremendous difficulties in creating sustainable and more soluble drugs (BCS class II). About 40% of oral dosage forms have formulation and development problems due to water insolubility. The rate of dissolving, absorption, distribution, and excretion of an active medicinal substance is determined by its solubility parameters. Based on their solubility, drugs are divided into four kinds under the BCS categorization system. BCS Class II and Class IV drugs have problems with solubility. Increasing both the bioavailability and the solubility of poorly soluble medications can be accomplished in several ways. Some techniques—like solid dispersion, solid complexation, liquisolid, hydrotropy, sonocrystallization, and self-emulsifying techniques—are commonly used for solubility augmentation. Until an orally active medication dissolves in the lining of the stomach and/or intestinal fluids, it cannot pass through the GI tract membrane and enter the bloodstream. Therefore, a medication that is insoluble in water will typically exhibit limited absorption by dissolution, and a medication that is weakly permeabilized via membranes would typically exhibit limited absorption through permeation. Consequently, improving the oral bioavailability of active substances is the focus of two areas of pharmaceutical research: (i) accelerating the process of dissolution and solubility of drugs that are poorly soluble in water, and (ii) accelerating the permeability of poorly permeable drugs.
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