Bezerra Kerolayne de Castro, Pinto Eduardo Costa, Cabral Lucio Mendes, de Sousa Valéria Pereira
Department of Pharmaceutics, Faculty of Pharmacy, Federal University of Rio de Janeiro.
Chem Pharm Bull (Tokyo). 2018;66(7):701-707. doi: 10.1248/cpb.c17-00933.
Gliclazide (GLZ) is a second generation hypoglycemic drug used for the treatment of Type 2 diabetes mellitus. The low solubility of GLZ has been described as the rate limiting step for drug dissolution and absorption, thus a prediction of its in vivo behavior based on a discriminative dissolution test should lead to a relevant in vitro-in vivo correlation (IVIVC). The aim of this study was to develop a dissolution method for GLZ modified-release (MR) tablets using an United States Pharmacopeia (USP) apparatus 3 through its evaluation by an IVIVC analysis. Various dissolution parameters were evaluated to establish an in vitro method for GLZ tablets. The final dissolution conditions, referred to as method 3, utilized a 400 µm mesh and 30 dips per minute over a total period of 10 h that included 1h in HCl media (pH 1.2), 2h in acetate buffer solution (pH 4.5), 1 h in phosphate buffer solution (PBS; pH 5.8), 5h in PBS (pH 6.8) and finally 1h in PBS (pH 7.2). The calculated point-to-point IVIVC (R=0.9970) was significantly greater than other methods. The robustness of method 3 suggests it could be applied to pharmaceutical equivalence studies and for quality control analyses of GLZ.
格列齐特（GLZ）是一种用于治疗2型糖尿病的第二代降糖药物。GLZ的低溶解度被认为是药物溶解和吸收的限速步骤，因此基于区分性溶出试验对其体内行为进行预测应能得出相关的体外-体内相关性（IVIVC）。本研究的目的是通过IVIVC分析评估，使用美国药典（USP）装置3开发一种用于GLZ缓释（MR）片剂的溶出方法。评估了各种溶出参数以建立GLZ片剂的体外方法。最终的溶出条件，称为方法3，使用400μm筛网，每分钟30次浸提，总时长10小时，包括在盐酸介质（pH 1.2）中1小时、在醋酸盐缓冲溶液（pH 4.5）中2小时、在磷酸盐缓冲溶液（PBS；pH 5.8）中1小时、在PBS（pH 6.8）中5小时，最后在PBS（pH 7.2）中1小时。计算得出的点对点IVIVC（R = 0.9970）显著高于其他方法。方法3的稳健性表明它可应用于药物等效性研究以及GLZ的质量控制分析。
