Iyer Sunil S, Barr William H, Karnes H Thomas
Department of Pharmaceutics, School of Pharmacy, Virginia Commonwealth University, Richmond, VA 23298-0533, USA.
J Pharm Biomed Anal. 2007 Feb 19;43(3):845-53. doi: 10.1016/j.jpba.2006.08.023. Epub 2006 Oct 11.
A variety of factors have been recognized that influence media optimization for drug release studies of implant dosage forms. Of primary importance is selection of a medium that physiologically mimics the milieu at the site of administration (a condition termed 'biorelevance'). We describe in this paper, the characterization of Hanks' balanced salts solution, with necessary modification, for application as a 'biorelevant' medium for in vitro release studies of a biodegradable, subcutaneous implant of naltrexone. A detailed investigation of changes in pH, osmolality and ultraviolet (UV) spectrum as a function of time and temperature was conducted. Variation in the parameters evaluated was found to be within acceptable limits. Validation of a simple and selective, high performance liquid chromatography (HPLC) assay method for naltrexone was carried out to evaluate stability. The calibration curves were linear from 0.16 to 20.00 microg ml(-1). Imprecision and inaccuracy were less than 2% and no interference was observed from degradation peaks. Stability studies of naltrexone indicated the media should be replaced every 7-8 days for real-time testing. This was applied to an investigation of in vitro drug release. The method has been proven to be suitable for investigation of naltrexone released from the implant.
人们已经认识到多种因素会影响植入剂剂型药物释放研究的介质优化。其中最重要的是选择一种能在生理上模拟给药部位环境的介质（这种情况称为“生物相关性”）。在本文中，我们描述了经过必要改良的汉克斯平衡盐溶液的特性，该溶液可作为生物可降解的纳曲酮皮下植入剂体外释放研究的“生物相关”介质。我们对pH值、渗透压和紫外光谱随时间和温度的变化进行了详细研究。结果发现，所评估参数的变化在可接受范围内。我们还对一种简单、选择性的纳曲酮高效液相色谱（HPLC）测定方法进行了验证，以评估其稳定性。校准曲线在0.16至20.00微克/毫升范围内呈线性。精密度和误差小于2%，未观察到降解峰产生干扰。纳曲酮的稳定性研究表明，为了进行实时测试，介质应每7 - 8天更换一次。这一方法已应用于体外药物释放研究。事实证明，该方法适用于研究从植入剂中释放的纳曲酮。
