Shim Hyunjin, Sah Hongkee
College of Pharmacy, Ewha Womans University, 52 Ewhayeodaegil, Seodaemun-gu, Seoul 03760, Korea.
Pharmaceutics. 2020 May 6;12(5):425. doi: 10.3390/pharmaceutics12050425.
As a non-halogenated dispersed solvent, ethyl acetate has been most commonly used for the manufacturing of poly-d,l-lactide--glycolide (PLGA) microspheres. However, ethyl acetate-based microencapsulation processes face several limitations. This study was aimed at proposing ethyl formate as an alternative. Evaluated in this study was the solvent qualification of ethyl formate and ethyl acetate for microencapsulation of a hydrophobic drug into PLGA microspheres. An oil-in-water emulsion solvent extraction technique was developed to load progesterone into PLGA microspheres. Briefly, right after emulsion droplets were temporarily stabilized, they were subject to primary solvent extraction. Appearing semisolid, embryonic microspheres were completely hardened through subsequent secondary solvent extraction. Changes in process parameters of the preparative technique made it possible to manipulate the properties of emulsion droplets, progesterone behavior, and microsphere quality. Despite the two solvents showing comparable Hansen solubility parameter distances toward PLGA, ethyl formate surpassed ethyl acetate in relation to volatility and water miscibility. These features served as advantages in the microsphere manufacturing process, helping produce PLGA microspheres with better quality in terms of drug crystallization, drug encapsulation efficiency, microsphere size homogeneity, and residual solvent content. The present ethyl formate-based preparative technique could be an attractive method of choice for the production of drug-loaded PLGA microspheres.
作为一种非卤代分散溶剂，乙酸乙酯最常用于聚（d，l-丙交酯-乙交酯）（PLGA）微球的制造。然而，基于乙酸乙酯的微囊化工艺面临若干限制。本研究旨在提出用甲酸乙酯作为替代物。本研究评估了甲酸乙酯和乙酸乙酯用于将疏水性药物微囊化到PLGA微球中的溶剂适用性。开发了一种水包油乳液溶剂萃取技术，将黄体酮载入PLGA微球。简而言之，乳液滴暂时稳定后，立即进行一次溶剂萃取。呈半固体状的胚胎微球通过随后的二次溶剂萃取完全硬化。制备技术工艺参数的改变使得调控乳液滴的性质、黄体酮行为和微球质量成为可能。尽管两种溶剂对PLGA的汉森溶解度参数距离相当，但甲酸乙酯在挥发性和与水的混溶性方面超过了乙酸乙酯。这些特性在微球制造过程中具有优势，有助于生产出在药物结晶、药物包封效率、微球尺寸均匀性和残留溶剂含量方面质量更好的PLGA微球。基于甲酸乙酯的现行制备技术可能是生产载药PLGA微球的一种有吸引力的选择方法。
