School of Pharmacy, University of Pittsburgh, Pittsburgh, PA, USA; Magee-Womens Research Institute, Pittsburgh, PA, USA.
Department of Chemical Engineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, PA, USA.
Int J Pharm. 2021 Mar 1;596:120261. doi: 10.1016/j.ijpharm.2021.120261. Epub 2021 Jan 21.
Currently, there is no compendial-level method to assess dissolution of particulate systems administered in the periodontal pocket. This work seeks to develop dissolution methods for extended release poly(lactic-co-glycolic acid) (PLGA) microspheres applied in the periodontal pocket. Arestin®, PLGA microspheres containing minocycline hydrochloride (MIN), is indicated for reduction of pocket depth in adult periodontitis. Utilizing Arestin® as a model product, two dissolution methods were developed: a dialysis set-up using USP apparatus 4 and a novel apparatus fabricated to simulate in vivo environment of the periodontal pocket. In the biorelevant method, the microspheres were dispersed in 250 μL of simulated gingival crevicular fluid (sGCF) which was enclosed in a custom-made dialysis enclosure. sGCF was continuously delivered to the device at a biorelevant flow rate and was collected daily for drug content analysis using UPLC. Both methods could discriminate release characteristics of a panel of MIN-loaded PLGA microspheres that differed in composition and process conditions. A mechanistic model was developed, which satisfactorily explained the release profiles observed using both dissolution methods. The developed methods may have the potential to be used as routine quality control tools to ensure batch-to-batch consistency and to support evaluation of bioequivalence for periodontal microspheres.
目前，还没有评估牙周袋中给予的颗粒系统溶解度的统篇级方法。这项工作旨在开发用于牙周袋中应用的延长释放聚（乳酸-共-乙醇酸）（PLGA）微球的溶解方法。Arestin®是一种载有盐酸米诺环素（MIN）的 PLGA 微球，用于减少成人牙周炎的牙周袋深度。利用 Arestin®作为模型产品，开发了两种溶解方法：使用 USP 仪器 4 的透析装置和一种新的装置，用于模拟牙周袋的体内环境。在生物相关方法中，将微球分散在 250μL 的模拟龈沟液（sGCF）中，sGCF 被封闭在定制的透析外壳中。sGCF 以生物相关流速连续输送到装置中，并每天收集一次用于使用 UPLC 进行药物含量分析。这两种方法都可以区分不同组成和工艺条件的载有 MIN 的 PLGA 微球的释放特性。开发了一种机械模型，该模型令人满意地解释了使用两种溶解方法观察到的释放曲线。开发的方法有可能被用作常规质量控制工具，以确保批间一致性，并支持牙周微球的生物等效性评估。
