Senjoti Faria Gias, Mahmood Syed, Jaffri Juliana Md, Mandal Uttam Kumar
Department of Pharmaceutical Technology, Kulliyyah of Pharmacy, International Islamic University Malaysia (IIUM), Kuantan, Malaysia.
Iran J Pharm Res. 2016 Winter;15(1):53-70.
An oral sustained-release floating tablet formulation of metformin HCl was designed and developed. Effervescence and swelling properties were attributed on the developed tablets by sodium bicarbonate and HPMC-PEO polymer combination, respectively. Tablet composition was optimized by response surface methodology (RSM). Seventeen (17) trial formulations were analyzed according to Box-Behnken design of experiment where polymer content of HPMC and PEO at 1: 4 ratio (A), amount of sodium bi-carbonate (B), and amount of SSG (C) were adopted as independent variables. Floating lag time in sec (Y1), cumulative percent drug released at 1 h (Y2) and 12 h (Y3) were chosen as response variables. Tablets from the optimized formulation were also stored at accelerated stability condition (40°C and 75% RH) for 3 months to assess their stability profile. RSM could efficiently optimize the tablet composition with excellent prediction ability. In-vitro drug release until 12 h, floating lag time, and duration of floating were dependent on the amount of three selected independent variables. Optimized tablets remained floating for more than 24 h with a floating lag time of less than 4 min. Based on best fitting method, optimized formulation was found to follow Korsmeyer-Peppas release kinetic. Accelerated stability study revealed that optimized formulation was stable for three months without any major changes in assay, dissolution profile, floating lag time and other physical properties.
设计并开发了盐酸二甲双胍口服缓释漂浮片制剂。分别通过碳酸氢钠和羟丙甲纤维素-聚氧化乙烯聚合物组合赋予所开发片剂泡腾和膨胀特性。采用响应面法（RSM）对片剂组成进行优化。根据Box-Behnken实验设计分析了17种试验制剂，其中采用1:4比例的羟丙甲纤维素和聚氧化乙烯的聚合物含量（A）、碳酸氢钠用量（B）和羟丙基淀粉甘醇酸用量（C）作为自变量。选择以秒为单位的漂浮滞后时间（Y1）、1小时（Y2）和12小时（Y3）时的药物累积释放百分比作为响应变量。还将优化制剂的片剂在加速稳定性条件（40°C和75%相对湿度）下储存3个月，以评估其稳定性。响应面法能够有效地优化片剂组成，具有出色的预测能力。体外药物释放至12小时、漂浮滞后时间和漂浮持续时间取决于三个选定自变量的用量。优化后的片剂漂浮超过24小时，漂浮滞后时间小于4分钟。基于最佳拟合方法，发现优化制剂符合Korsmeyer-Peppas释放动力学。加速稳定性研究表明，优化制剂在三个月内稳定，含量测定、溶出曲线、漂浮滞后时间和其他物理性质均无重大变化。
