Microneedle created in skin in situ forming gels depot; an alternate approach to the sustained transdermal delivery of colchicine

Abstract

Colchicine (CLC) is a commonly used medication in prevention and treatment of acute gout condition via oral route. However its oral administrations pose several gastrointestinal (GI) adverse effects. In current study, an alternate combinatorial approach of microneedles patch and in skin forming gel depots were evaluated for sustained CLC delivery through skin using CLC loaded non-ionic amphiphilic triblock pluronic-127 thermoresponsive poloxamers. In first phase, to validate the development of in situ forming depots, the phase transition of pluronic-127 from the sol-gel state was examined using AR2000 rheometer. In second phase, microneedles patches (MAPs) were fabricated via casting method utilizing (19 × 19) laser-engineered silicone micromoulds from varied biocompatible polymer blends such as Gantrez S-97, Poly-vinyl alcohol, Polyethelene glycol 10000 and Poly (vinylpyrollidone) at various concentrations. For optimized MAPs, the mechanical strength, in skin dissolution kinetics and moisture contents were determined. From mechanical testing PVP and PVA MAPs showed more brittle nature and highest loss of MAPs reduction in comparison to Gantrez® MAPs. Optimized MAPs (Gantrez®) based on high mechanical strength were utilized as a microporation source in rabbit skin. In comparison to PVA and PVP, Gantrez® MAPs showed slow dissolution kinetics and resist dissolution for 540 s. Optical coherence tomography (OCT) quantified the penetration depth of Gantrez® MAPs in newborn rabbit skin at 591 μm. Increased in TEWL values after Gantrez® MAPs treatment confirmed the pores formation in skin. Ex-vivo permeation analysis showed that 25 % w/w CLC loaded PF127® gel showed controlled and prolonged drug permeation across microporated skin for 84 h in comparison to untreated skin. The distribution of PF127 gel solution in treated skin samples was confirmed by tracking fluorescence using confocal microscopy. Results shows that MAPs created in skin micropores can be used as CLC depots and sustained effects can be achieved by successfully avoiding oral route and GI adverse effects.