Razavi Mahboubeh, Karimian Hamed, Yeong Chai Hong, Fadaeinasab Mehran, Khaing Si Lay, Chung Lip Yong, Mohamad Haron Didi Erwandi B, Noordin Mohamed Ibrahim
Department of Pharmacy.
University Malaya Research Imaging Centre and Department of Biomedical Imaging, Faculty of Medicine.
Drug Des Devel Ther. 2016 Dec 19;11:1-15. doi: 10.2147/DDDT.S115466. eCollection 2017.
This study aimed to formulate floating gastroretentive tablets containing metformin hydrochloric acid (HCl), using various grades of hydrogel such as tamarind powders and xanthan to overcome short gastric residence time of the conventional dosage forms. Different concentrations of the hydrogels were tested to determine the formulation that could provide a sustained release of 12 h. Eleven formulations with different ratios of tamarind seed powder/tamarind kernel powder (TKP):xanthan were prepared. The physical parameters were observed, and in vitro drug-release studies of the prepared formulations were carried out. Optimal formulation was assessed for physicochemical properties, thermal stability, and chemical interaction followed by in vivo gamma scintigraphy study. MKP3 formulation with a TKP:xanthan ratio of 3:2 was found to have 99.87% release over 12 h. Furthermore, in vivo gamma scintigraphy study was carried out for the optimized formulation in healthy New Zealand White rabbits, and the pharmacokinetic parameters of developed formulations were obtained. SmO was used to trace the profile of release in the gastrointestinal tract of the rabbits, and the drug release was analyzed. The time () at which the maximum concentration of metformin HCl in the blood () was observed, and it was extended four times for the gastroretentive formulation in comparison with the formulation without polymers. and the half-life were found to be within an acceptable range. It is therefore concluded that MKP3 is the optimal formulation for sustained release of metformin HCl over a period of 12 h as a result of its floating properties in the gastric region.
本研究旨在制备含盐酸二甲双胍的胃内滞留漂浮片，使用罗望子粉和黄原胶等不同等级的水凝胶来克服传统剂型胃内滞留时间短的问题。测试了不同浓度的水凝胶，以确定能够提供12小时缓释的制剂。制备了11种不同比例的罗望子种子粉/罗望子仁粉（TKP）:黄原胶的制剂。观察了物理参数，并对所制备制剂进行了体外药物释放研究。对最佳制剂进行了理化性质、热稳定性和化学相互作用评估，随后进行了体内γ闪烁扫描研究。发现TKP:黄原胶比例为3:2的MKP3制剂在12小时内释放率达99.87%。此外，对优化后的制剂在健康新西兰白兔体内进行了γ闪烁扫描研究，获得了所开发制剂的药代动力学参数。用锝[99mTc]标记物（SmO）追踪兔胃肠道内的释放情况，并对药物释放进行了分析。观察到血液中盐酸二甲双胍最大浓度（Cmax）出现的时间（tmax），与不含聚合物的制剂相比，胃内滞留制剂的tmax延长了四倍。且半衰期在可接受范围内。因此得出结论，由于MKP3在胃区域具有漂浮特性，它是盐酸二甲双胍12小时持续释放的最佳制剂。
