Natural Products Laboratory, Institute of Biology Leiden, Leiden University, 2333 Leiden, The Netherlands.
Tiofarma, 3261 Oud-Beijerland, The Netherlands.
Molecules. 2021 Apr 30;26(9):2645. doi: 10.3390/molecules26092645.
Some medicines are poorly soluble in water. For tube feeding and parenteral administration, liquid formulations are required. The discovery of natural deep eutectic solvents (NADES) opened the way to potential applications for liquid drug formulations. NADES consists of a mixture of two or more simple natural products such as sugars, amino acids, organic acids, choline/betaine, and poly-alcohols in certain molar ratios. A series of NADES with a water content of 0-30% () was screened for the ability to solubilize (in a stable way) some poorly water-soluble pharmaceuticals at a concentration of 5 mg/mL. The results showed that NADES selectively dissolved the tested drugs. Some mixtures of choline-based NADES, acid-neutral or sugars-based NADES could dissolve chloral hydrate (dissociated in water), ranitidine·HCl (polymorphism), and methylphenidate (water insoluble), at a concentration of up to 250 mg/mL, the highest concentration tested. Whereas a mixture of lactic-acid-propyleneglycol could dissolve spironolacton and trimethoprim at a concentration up to 50 and 100 mg/mL, respectively. The results showed that NADES are promising solvents for formulation of poorly water-soluble medicines for the development of parenteral and tube feeding administration of non-water-soluble medicines. The chemical stability and bioavailability of these drug in NADES needs further studies.
有些药物在水中的溶解度很差。对于管饲和肠外给药,需要液体制剂。天然深共晶溶剂 (NADES) 的发现为潜在的液体药物制剂应用开辟了道路。NADES 由两种或多种简单天然产物(如糖、氨基酸、有机酸、胆碱/甜菜碱和多元醇)以一定摩尔比混合而成。筛选了一系列水含量为 0-30%() 的 NADES,以评估其在 5mg/mL 浓度下稳定溶解一些水溶性差的药物的能力。结果表明,NADES 选择性溶解了测试的药物。一些基于胆碱的 NADES、酸中和或基于糖的 NADES 的混合物可以溶解水合氯醛(在水中离解)、盐酸雷尼替丁(多晶型物)和哌甲酯(不溶于水),浓度高达 250mg/mL,这是测试的最高浓度。而丙二醇乳酸混合物可以分别溶解螺内酯和甲氧苄啶,浓度高达 50 和 100mg/mL。结果表明,NADES 是一种很有前途的用于制备水溶性差的药物的溶剂,可用于开发非水溶性药物的肠外和管饲给药。这些药物在 NADES 中的化学稳定性和生物利用度需要进一步研究。
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