Mitchell Shawn A, Balwinski Karen M
Water Soluble Polymers, The Dow Chemical Company, Midland, Michigan 48674, USA.
J Pharm Sci. 2008 Jun;97(6):2277-85. doi: 10.1002/jps.21145.
Substitution level, particle size, and molecular weight are key properties of hypromellose (HPMC) known to be important to its performance in pharmaceutical-controlled release applications. The hypromellose monographs indirectly specify acceptable ranges for the molecular weight of HPMC products, expressed as the apparent viscosity of a 2% aqueous solution. The purpose of this study was to provide a framework to systematically investigate the amount of drug release variability that might be expected for typical controlled release formulations over the monograph viscosity ranges for hypromellose. An approach to estimate the expected drug release variability was developed based on scaling laws in the literature. New experimental data were generated with pentoxifylline, theophylline, and hydrochlorothiazide as model drugs to explore the applicability of this approach to a range of formulations. This methodology predicted that drug release variability over the United States Pharmacopeia (USP) viscosity ranges would be greatest for the lower viscosity grades of hypromellose, such as E50 and K100 LV. Drug release variability due to hypromellose viscosity variations is expected to be larger for formulations having substantial contributions from erosional drug release, and smaller for formulations with a predominantly diffusional drug release mechanism. These predictions need to be validated experimentally.
取代度、粒径和分子量是羟丙甲纤维素（HPMC）的关键特性，已知这些特性对其在药物控释应用中的性能很重要。羟丙甲纤维素各论间接规定了HPMC产品分子量的可接受范围，以2%水溶液的表观粘度表示。本研究的目的是提供一个框架，以系统地研究在羟丙甲纤维素各论粘度范围内，典型控释制剂可能预期的药物释放变异性量。基于文献中的标度定律，开发了一种估计预期药物释放变异性的方法。以己酮可可碱、茶碱和氢氯噻嗪为模型药物生成了新的实验数据，以探索该方法对一系列制剂的适用性。该方法预测，在美国药典（USP）粘度范围内，羟丙甲纤维素较低粘度等级（如E50和K100 LV）的药物释放变异性最大。对于侵蚀性药物释放起主要作用的制剂，由于羟丙甲纤维素粘度变化导致的药物释放变异性预计会更大，而对于以扩散为主的药物释放机制的制剂则较小。这些预测需要通过实验进行验证。
