Patel Salin Gupta, Bummer Paul M
Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 789 South Limestone Street, Lexington, Kentucky, 40536-0596, USA.
AAPS PharmSciTech. 2016 Oct;17(5):1182-91. doi: 10.1208/s12249-015-0451-5. Epub 2015 Dec 3.
This report describes the development of a chromatographic method for the simultaneous quantification of a polymer, hydroxypropyl methylcellulose (HPMC), and a surfactant, dodecyl β-D-maltoside (DM), that are commonly used in the physical stabilization of pharmaceutical formulations such as nanosuspensions and solid dispersions. These excipients are often challenging to quantify due to the lack of chromophores. A reverse phase size exclusion chromatography (SEC) with evaporative light scattering detector (ELSD) technique was utilized to develop an accurate and robust assay for the simultaneous quantification of HPMC and DM in a nanosuspension formulation. The statistical design of experiments was used to determine the influence of critical ELSD variables including temperature, pressure, and gain on accuracy, precision, and sensitivity of the assay. A robust design space was identified where it was determined that an increase in the temperature of the drift tube and gain of the instrument increased the accuracy and precision of the assay and a decrease in the nebulizer pressure value increased the sensitivity of the assay. In the optimized design space, response data showed that the assay could quantify HPMC and DM simultaneously with good accuracy, precision, and reproducibility. Overall, SEC-ELSD proved to be a powerful technique for the simultaneous quantification of HPMC and DM. This technique can be used to quantify the amount of HPMC and DM in nanosuspensions, which is critical to understanding their effects on the physical stability of nanosuspensions.
本报告描述了一种色谱方法的开发，该方法用于同时定量测定聚合物羟丙基甲基纤维素（HPMC）和表面活性剂十二烷基β-D-麦芽糖苷（DM），这两种物质常用于纳米混悬液和固体分散体等药物制剂的物理稳定化。由于缺乏发色团，这些辅料的定量分析往往具有挑战性。采用带蒸发光散射检测器（ELSD）的反相尺寸排阻色谱（SEC）技术，开发了一种准确且稳健的方法，用于同时定量测定纳米混悬液制剂中的HPMC和DM。利用实验的统计设计来确定ELSD关键变量（包括温度、压力和增益）对该分析方法的准确性、精密度和灵敏度的影响。确定了一个稳健的设计空间，其中发现漂移管温度和仪器增益的增加会提高分析方法的准确性和精密度，而雾化器压力值的降低会提高分析方法的灵敏度。在优化的设计空间中，响应数据表明该分析方法能够以良好的准确性、精密度和重现性同时定量测定HPMC和DM。总体而言，SEC-ELSD被证明是一种用于同时定量测定HPMC和DM的强大技术。该技术可用于定量纳米混悬液中HPMC和DM的含量，这对于理解它们对纳米混悬液物理稳定性的影响至关重要。
