Department of Pharmaceutics, Al-Ameen College of Pharmacy, Bangalore, India.
Drug Dev Ind Pharm. 2013 Jan;39(1):117-27. doi: 10.3109/03639045.2012.662503. Epub 2012 Feb 28.
Metformin hydrochloride (MH), a biguanide antidiabetic, is the drug of choice in obese patients. It is well absorbed from the upper part of gastrointestinal tract and has oral bioavailability of 50% to 60%. The objective of this study was to formulate MH into floating microspheres in order to increase its residence time at the site of absorption and thus improve its bioavailability; and to extend the duration of action along with possibilities of dose reduction. Microspheres were prepared by emulsion solvent evaporation method and evaluated for particle size, entrapment efficiency, buoyancy, and in vitro release; and further characterized by powder X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy, and differential scanning calorimetry. The pharmacokinetic and pharmacodynamic evaluation of selected formulation was carried out in male Wistar diabetic rats. The data was statistically analyzed by unpaired t-test. A 3.5-fold increase in relative bioavailability was observed. The prolongation of half-life (t(1/2)) from 4.5 ± 2.41 h to 14.12 ± 4.81 h indicated extended duration of action. Oral glucose tolerance test (OGTT) was analyzed by one-way analysis of variance followed by Dunnet multiple comparison test, a significant decrease (p < 0.05) in the blood glucose levels was observed when formulations were compared with control rats. Hence, MH floating microspheres were tested at 50 mg/kg and 100 mg/kg body weight, OGTT data showed nonsignificant difference (p >0.05). In conclusion, an effective oral antidiabetics treatment can be achieved by formulating MH into floating microspheres which results in increase in bioavailability along with extended duration of action resulting in possible reduction in dose.
盐酸二甲双胍（MH）是一种双胍类抗糖尿病药物，是肥胖患者的首选药物。它在上消化道被很好地吸收，口服生物利用度为 50%至 60%。本研究的目的是将 MH 制成漂浮微球，以增加其在吸收部位的停留时间，从而提高其生物利用度；并延长作用时间，同时有可能减少剂量。微球采用乳化溶剂蒸发法制备，并对粒径、包封效率、漂浮性和体外释放进行评价；进一步通过粉末 X 射线衍射、傅里叶变换红外光谱、扫描电子显微镜和差示扫描量热法进行表征。对选定制剂进行了雄性 Wistar 糖尿病大鼠的药代动力学和药效学评价。数据通过配对 t 检验进行统计学分析。相对生物利用度提高了 3.5 倍。半衰期（t(1/2)）从 4.5±2.41 h 延长至 14.12±4.81 h，表明作用时间延长。口服葡萄糖耐量试验（OGTT）通过单因素方差分析和 Dunnet 多重比较检验进行分析，与对照大鼠相比，制剂组的血糖水平显著降低（p<0.05）。因此，以 50mg/kg 和 100mg/kg 体重测试 MH 漂浮微球，OGTT 数据显示无显著性差异（p>0.05）。总之，将 MH 制成漂浮微球可以有效提高生物利用度，延长作用时间，从而有可能减少剂量，实现有效的口服抗糖尿病治疗。
