Department of Pharmaceutical Sciences, University of Connecticut, 69 N Eagleville Road, Unit 3092, Storrs, CT 06269, United States.
Int J Pharm. 2012 Jan 17;422(1-2):341-8. doi: 10.1016/j.ijpharm.2011.10.020. Epub 2011 Oct 13.
Dexamethasone loaded poly(lactic-co-glycolic acid) (PLGA) microsphere/PVA hydrogel composites have been investigated as an outer drug-eluting coating for implantable devices such as glucose sensors to counter negative tissue responses to implants. The objective of this study was to develop a discriminatory, accelerated in vitro release testing method for this drug-eluting coating using United States Pharmacopeia (USP) apparatus 4. Polymer degradation and drug release kinetics were investigated under "real-time" and accelerated conditions (i.e. extreme pH, hydro-alcoholic solutions and elevated temperatures). Compared to "real-time" conditions, the initial burst and lag phases were similar using hydro-alcoholic solutions and extreme pH conditions, while the secondary apparent zero-order release phase was slightly accelerated. Elevated temperatures resulted in a significant acceleration of dexamethasone release. The accelerated release data were able to predict "real-time" release when applying the Arrhenius equation. Microsphere batches with faster and slower release profiles were investigated under "real-time" and elevated temperature (60°C) conditions to determine the discriminatory ability of the method. The results demonstrated both the feasibility and the discriminatory ability of this USP apparatus 4 method for in vitro release testing of drug loaded PLGA microsphere/PVA hydrogel composites. This method may be appropriate for similar drug/device combination products and drug delivery systems.
载有地塞米松的聚（丙交酯-乙交酯）（PLGA）微球/PVA 水凝胶复合材料已被研究作为植入式设备（如葡萄糖传感器）的外药物洗脱涂层，以对抗植入物引起的负面组织反应。本研究的目的是开发一种用于该药物洗脱涂层的鉴别性、加速体外释放测试方法，使用美国药典（USP）装置 4。在“实时”和加速条件下（即极端 pH 值、水醇溶液和升高的温度）研究了聚合物降解和药物释放动力学。与“实时”条件相比，水醇溶液和极端 pH 值条件下的初始突释和迟滞期相似，而二次明显的零级释放期略有加速。升高的温度导致地塞米松释放显著加速。应用阿仑尼乌斯方程时，加速释放数据能够预测“实时”释放。在“实时”和高温（60°C）条件下研究了具有更快和更慢释放曲线的微球批次，以确定该方法的鉴别能力。结果表明，USP 装置 4 法用于载药 PLGA 微球/PVA 水凝胶复合材料的体外释放测试具有可行性和鉴别能力。该方法可能适用于类似的药物/器械组合产品和药物输送系统。
