期刊
JOURNAL OF CONTROLLED RELEASE
卷 285, 期 -, 页码 142-151出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jconrel.2018.07.009
关键词
Metformin HCl; Hydrogel-forming microneedles; Transdermal delivery
资金
- School of Pharmacy, Applied Science Private University, Amman, Jordan
- Wellcome Trust [WT094085MA]
We investigated, for the first time, the potential for a hydrogel-forming microneedle (MN) patch to deliver the high-dose drug metformin HCl transdermally in a sustained manner. This may minimize some gastrointestinal side effects and small intestine absorption variations associated with oral delivery. Patches (two layers) were assembled from a lyophilised drug reservoir layer, with the MN layer made from aqueous blend of 20% w/w poly (methylvinylether-co-maleic acid) crosslinked by esterification with 7.5% w/w poly (ethylene glycol) 10,000 Da. > 90% of metformin was recovered from homogeneous drug reservoirs. Drug reservoir dissolution time in PBS (pH 7.4) was < 10 min. MN penetrated a validated skin model Parafilm (R) M consistently. Permeation of metformin HCl across dermatomed neonatal porcine skin in vitro was enhanced by using MN. The combined MN and metformin HCl reservoir patch (containing 75 mg or 50 mg metformin HCl, respectively) delivered 9.71 +/- 2.22 mg and 10.04 +/- 1.92 mg at 6 h, respectively, and 28.15 +/- 2.37 mg and 23.25 +/- 3.58 mg at 24 h, respectively. In comparison, 0.34 +/- 0.39 mg and 0.85 +/- 0.68 mg was delivered at 6 h, respectively, and 0.39 +/- 0.39 mg and 1.01 +/- 0.84 mg was delivered at 24 h, respectively, from a control set-up employing only the drug reservoirs. In vivo, metformin HCl was detected in rat plasma at 1 h post MN application at a concentration of 0.62 +/- 0.51 mu g/mL, increasing to 3.76 +/- 2.58 mu g/ml at 3 h. A maximal concentration of 3.77 +/- 2.09 mu g/ml was achieved at 24 h. Css was 3.2 mu g/mL. Metformin transdermal bioavailability using MNs was estimated as 30%. Hydrogel-forming MN are a promising technology that has demonstrated successful transdermal delivery of metformin HCl. Potential clearly exists for administration of other high-dose drugs using this system.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据