College of Pharmaceutical Sciences & Key Laboratory of Pharmaceutical Quality Control of Hebei Province, Hebei University, Baoding, China.
Drug Dev Ind Pharm. 2022 Aug;48(8):397-405. doi: 10.1080/03639045.2022.2120493. Epub 2022 Sep 8.
The solubility of glimepiride (GM) was improved from 1.6 μg/mL to 22.0 mg/mL when GM and meglumine (MU) complexes were prepared. Therefore, transdermal hydrogels of GM Carbopol (GM-CP) and GM hydroxypropyl methylcellulose pullulan (GM-HPMC-Pu) were prepared successfully utilizing the improved drug solubility by GM-MU. Based on a single factor experiment and response surface methodology, two kinds of hydrogel formulations were optimized by drug release studies . The optimized GM-CP hydrogel was composed of GM, a mixture of azone and oleic acid (1:1, 2.6%, ) and carbopol 940 (1%, ). The GM-HPMC-Pu hydrogel was developed using GM, HPMC (3.5%, ), Pu (1.5%, ), glycerol (5%, ), azone (2.9%, ) and oleic acid (2.6%, ). The study of hydrogels was performed using rabbits. The results indicated that the drug could sustain release from GM-CP or GM-HPMC-Pu hydrogel and maintain the high plasma concentration for 48 h. Compared with commercial GM tablets, the relative bioavailability of GM-CP and GM-HPMC-Pu hydrogel reached 48% and 133%, respectively. Moreover, the drug release could well predict its absorption . There was a good correlation (≥0.966) in GM hydrogel between the drug release and transdermal absorption . Therefore, a novel GM hydrogel dosage form may be considered to design.
当将格列美脲（GM）与葡甲胺（MU）制成复合物时，其溶解度从 1.6μg/mL 提高到 22.0mg/mL。因此，成功地利用 GM-MU 提高了药物的溶解度，制备了 GM 卡波姆（GM-CP）和 GM 羟丙基甲基纤维素普鲁兰（GM-HPMC-Pu）的透皮水凝胶。基于单因素实验和响应面法，通过药物释放研究对两种水凝胶配方进行了优化。优化的 GM-CP 水凝胶由 GM、氮酮和油酸（1:1，2.6%）的混合物和卡波姆 940（1%）组成。GM-HPMC-Pu 水凝胶是使用 GM、HPMC（3.5%）、普鲁兰（1.5%）、甘油（5%）、氮酮（2.9%）和油酸（2.6%）开发的。通过兔子进行水凝胶研究。结果表明，药物可以从 GM-CP 或 GM-HPMC-Pu 水凝胶中持续释放，并维持 48h 的高血浆浓度。与商业 GM 片剂相比，GM-CP 和 GM-HPMC-Pu 水凝胶的相对生物利用度分别达到 48%和 133%。此外，药物释放可以很好地预测其吸收。GM 水凝胶中的药物释放与透皮吸收之间存在良好的相关性（≥0.966）。因此，可以考虑设计一种新型 GM 水凝胶剂型。
