RESUMO
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) 10,000â¯Da. >90% of metformin was recovered from homogeneous drug reservoirs. Drug reservoir dissolution time in PBS (pHâ¯7.4) was <10â¯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 75â¯mg or 50â¯mg metformin HCl, respectively) delivered 9.71⯱â¯2.22â¯mg and 10.04⯱â¯1.92â¯mg at 6â¯h, respectively, and 28.15⯱â¯2.37â¯mg and 23.25⯱â¯3.58â¯mg at 24â¯h, respectively.In comparison, 0.34⯱â¯0.39â¯mg and 0.85⯱â¯0.68â¯mg was delivered at 6â¯h, respectively, and 0.39⯱â¯0.39â¯mg and 1.01⯱â¯0.84â¯mg was delivered at 24â¯h, respectively, from a control set-up employing only the drug reservoirs. In vivo, metformin HCl was detected in rat plasma at 1â¯h post MN application at a concentration of 0.62⯱â¯0.51⯵g/mL, increasing to 3.76⯱â¯2.58⯵g/ml at 3â¯h. A maximal concentration of 3.77⯱â¯2.09⯵g/ml was achieved at 24â¯h. Css was 3.2⯵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.