Meeus Joke, Scurr David J, Appeltans Bernard, Amssoms Katie, Annaert Pieter, Davies Martyn C, Roberts Clive J, Van den Mooter Guy
Drug Delivery and Disposition, KU Leuven, Leuven, Belgium.
Laboratory of Biophysics and Surface Analysis, School of Pharmacy, The University of Nottingham, Nottingham, United Kingdom.
Eur J Pharm Biopharm. 2015 Feb;90:22-9. doi: 10.1016/j.ejpb.2014.11.009. Epub 2014 Nov 20.
Understanding and controlling the in vitro release behavior of a formulation is a first step toward rationalized selection of a solubility enhancing formulation strategy with a desired release profile in vivo. Therefore six model formulations, representing three different formulation strategies, were physicochemically analyzed and their in vitro release was determined. Solid dispersions based on a PLGA/PVP matrix were compared to solid dispersions in a pure PLGA matrix. Additionally these solid dispersion strategies were compared to the strategy of particle size reduction by means of an API microsuspension. Depending on composition and manufacturing method, formulations varied in particle size, porosity, phase behavior, surface coverage and physical state of the API. This resulted in observed differences in their in vitro release profile. For the various formulation strategies tested both a porous PLGA-based formulation and PLGA/PVP-based formulations, resulted in vitro in sustained release of the poorly soluble API with over 50% of drug released after 24h. For PLGA-based formulations the porosity was identified as a critical parameter influencing in vitro drug release. For the PLGA/PVP-based formulations the release rate can be tailored by the amount of PLGA present. Particle size reduction resulted in immediate total drug release.
了解和控制制剂的体外释放行为是合理选择具有体内所需释放曲线的溶解度增强制剂策略的第一步。因此，对代表三种不同制剂策略的六种模型制剂进行了物理化学分析，并测定了它们的体外释放情况。将基于PLGA/PVP基质的固体分散体与纯PLGA基质中的固体分散体进行了比较。此外，还将这些固体分散体策略与通过API微悬浮液减小粒径的策略进行了比较。根据组成和制造方法，制剂在粒径、孔隙率、相行为、表面覆盖率和API的物理状态方面存在差异。这导致它们的体外释放曲线出现观察到的差异。对于测试的各种制剂策略，无论是基于多孔PLGA的制剂还是基于PLGA/PVP的制剂，在体外均导致难溶性API的持续释放，24小时后超过50%的药物释放。对于基于PLGA的制剂，孔隙率被确定为影响体外药物释放的关键参数。对于基于PLGA/PVP的制剂，释放速率可以通过PLGA的含量进行调整。粒径减小导致药物立即完全释放。
