Abstract
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® 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 μg/mL, increasing to 3.76 ± 2.58 μg/ml at 3 h. A maximal concentration of 3.77 ± 2.09 μg/ml was achieved at 24 h. Css was 3.2 μg/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.
Highlights
Hydrogel-forming microneedle arrays (MNs) are typically fabricated from aqueous blends of poly and poly via a micromoulding process using silicone moulds that have been prepared by laser engineering technology [1,2]
This study investigates the ability of hydrogel-forming MNs to deliver metformin HCl transdermally in vitro and in vivo
This indicated that MN arrays have sufficient mechanical strength and are unlikely to be broken upon insertion into the skin
Summary
Hydrogel-forming microneedle arrays (MNs) are typically fabricated from aqueous blends of poly (methylvinylether/maleic acid) and poly (ethylene glycol) via a micromoulding process using silicone moulds that have been prepared by laser engineering technology [1,2]. Hydrogel-forming MNs, once applied to the skin, can be withdrawn intact, leaving no polymeric residues behind This represents a considerable advantage in comparison to dissolving MNs [5]. Hydrogel-forming MNs could overcome some of the limitations typically associated with coated MNs, such as extremely reduced MN loading capacity, difficulty in achieving accurate drug coating and controlling rate and extent of drug release [1]. This technology offers a simplified one-step application process, in comparison to uncoated solid MNs that require a two-step application [1]
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