Patel Meenakshi, Shelke Santosh, Surti Naazneen, Panzade Prabhakar, Al-Keridis Lamya Ahmed, Upadhyay Tarun Kumar, Alshammari Nawaf, Saeed Mohd
Department of Pharmaceutics, School of Pharmacy, Faculty of Pharmacy, Parul University, Waghodia, India.
Department of Pharmaceutics, Srinath College of Pharmacy, Aurangabad, India.
Front Pharmacol. 2023 Mar 15;14:1140351. doi: 10.3389/fphar.2023.1140351. eCollection 2023.
The present research is focused on developing floating matrix tablets of mitiglinide to prolong its gastric residence time for better absorption. Gastroretentive tablets were prepared using a direct compression technique with hydroxypropyl methylcellulose K15M (HPMC K15M) and sodium alginate as matrix-forming polymers and sodium bicarbonate as the gas-forming agent. A 3 full factorial design was adopted to optimize the flotation and release profile of the drug. The concentration of HPMC K15M and sodium alginate were taken as the independent variables, and the floating lag time, time required for 50% drug release, and time required for 90% drug release were taken as dependent variables. The compatibility between drug and excipients was assessed by Fourier transform infrared (FTIR) spectroscopy. The prepared tablets were evaluated for different parameters such as hardness, friability, drug content, floating time, dissolution, and stability. Dissolution data were analyzed using various kinetic models to ascertain the mechanism of drug release. Finally, a radiographic study was conducted to estimate the retention time of the optimized floating matrix tablets of mitiglinide inside the body. The results revealed that all the physical properties of the developed formulations were within standard limits. The formulation M3, with the maximum amount of both independent variables, was considered to be the optimized formulation based on the desirability value. In addition, the optimized M3 formulation showed stability for over 6 months, as evidenced by insignificant changes in lag time, drug release pattern, and other physical properties. Furthermore, radiographic examination indicated that the tablets remained afloat in gastric fluid for up to 12 h in the rabbit's stomach. In conclusion, the developed floating matrix tablet of mitiglinide could be regarded as a promising formulation that could release the drug in the stomach at a controlled rate and, hence, offer better management of type II diabetes.
本研究聚焦于开发米格列奈的漂浮型骨架片，以延长其在胃中的滞留时间，实现更好的吸收。采用直接压片技术，以羟丙基甲基纤维素K15M（HPMC K15M）和海藻酸钠作为骨架形成聚合物，碳酸氢钠作为产气剂，制备胃滞留片。采用三因素全因子设计优化药物的漂浮和释放特性。将HPMC K15M和海藻酸钠的浓度作为自变量，将漂浮滞后时间、药物释放50%所需时间和药物释放90%所需时间作为因变量。通过傅里叶变换红外（FTIR）光谱评估药物与辅料之间的相容性。对制备的片剂进行不同参数的评估，如硬度、脆碎度、药物含量、漂浮时间、溶出度和稳定性。使用各种动力学模型分析溶出数据，以确定药物释放机制。最后，进行影像学研究，以估计优化后的米格列奈漂浮型骨架片在体内的滞留时间。结果表明，所开发制剂的所有物理性质均在标准限度内。基于可取性值，具有最大自变量含量的制剂M3被认为是优化制剂。此外，优化后的M3制剂显示出超过6个月的稳定性，滞后时间、药物释放模式和其他物理性质无显著变化即为证明。此外，影像学检查表明，片剂在兔胃中的胃液中可漂浮长达12小时。总之，所开发的米格列奈漂浮型骨架片可被视为一种有前景的制剂，能够以可控速率在胃中释放药物，从而更好地治疗II型糖尿病。
