Mendes Thamara de Carvalho, Simon Alice, Menezes Jaqueline Correia Villaça, Pinto Eduardo Costa, Cabral Lucio Mendes, de Sousa Valeria Pereira
Department of Drugs and Pharmaceutics, Faculty of Pharmacy, Federal University of Rio de Janeiro.
Chem Pharm Bull (Tokyo). 2019;67(1):23-31. doi: 10.1248/cpb.c18-00579.
Metformin is a euglycemic drug for the treatment of type 2 diabetes mellitus. To date, there are 13 dissolution methodologies described in the U.S. Pharmacopoeia (USP) to evaluate the release profile of metformin from extended-release tablets utilizing either a USP apparatus 1 (basket) or 2 (paddle). In the absence of a protocol for a USP apparatus 3 (reciprocating cylinder), the goal of this work was to develop an in vitro dissolution method for metformin extended-release tablets based on an in vivo-in vitro correlation (IVIVC). Following a systematic evaluation, a final dissolution method, M4, was defined. It applied 30 dips per minute (dpm) over a total period of 10 h into a series of solutions that included 2 h in HCl media (pH 1.2), 1 h in an acetate buffer solution (pH 4.5), 1 h in phosphate buffer solution (PBS) (pH 5.8) and 6 h in PBS (pH 6.8). This method showed a significant IVIVC with a calculated R > 0.98 (point-to-point correlation, Level A) and it was successfully used as a tool to assist in the development of generic extended release formulations for metformin consisting of a lipophilic matrix system.
二甲双胍是一种用于治疗2型糖尿病的血糖正常化药物。迄今为止，美国药典（USP）中描述了13种溶出方法，用于评估二甲双胍缓释片的释放曲线，这些方法使用USP装置1（篮法）或装置2（桨法）。由于缺乏针对USP装置3（往复筒法）的方案，本研究的目的是基于体内-体外相关性（IVIVC）开发一种二甲双胍缓释片的体外溶出方法。经过系统评估，确定了最终的溶出方法M4。该方法以每分钟30次浸入（dpm）的速度，在10小时的总时间段内，依次浸入一系列溶液中，包括在盐酸介质（pH 1.2）中浸泡2小时、在醋酸盐缓冲溶液（pH 4.5）中浸泡1小时、在磷酸盐缓冲溶液（PBS）（pH 5.8）中浸泡1小时以及在PBS（pH 6.8）中浸泡6小时。该方法显示出显著的IVIVC，计算得出的R>0.98（点对点相关性，A级），并且成功用作辅助开发由亲脂性基质系统组成的二甲双胍通用缓释制剂的工具。
