Fabrication of Dissolvable Microneedle Patches Using an Innovative Laser-Cut Mould Design to Shortlist Potentially Transungual Delivery Systems: In Vitro Evaluation.

Abstract

There has been a great interest towards transungual delivery systems due to limited drug penetration for the treatment of nail diseases. More important, antifungal oral medicaments used may cause serious side effects including liver damage. Therefore, we propose non-oral dissolvable microneedle (MN) patch to strike the poor permeability of the nail. We report the design of MN patch mould using a laser-cutting machine and solvent casting of several hydrophilic polymers to fabricate these MN patches. Formulations were evaluated for their in vitro release and penetration properties and selected based on physical characterization for compatibility (differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD)), dimension repeatability and drug content uniformity. A 72-array of cone-shaped MN patch mould was successfully constructed on polymethylmethacrylate sheets. Interval and frequency of laser exposure were pivotal to determine the needle sharpness, attained unexpectedly at a low level of circa 30μm. F1 platform of polyvinyl alcohol, kollicoat IR®, ethylene glycol and gelatin showed circa 74% penetration of methylhydroxy-4-benzoate (F1(A)) over 24h, whereas F2 (same as F1-A with the addition of poloxamer 338) resulted in an almost 42% of this drug retention in the bovine hoof (24h). Both formulations are likely to be useful for onychomycosis treatment. F1 polymers also afford enhanced permeability (almost 73.5% after 24h) of terbinafine hydrochloride into the hoof (F1(B)). However, F3 (chitosan, gelatin and ethylene glycol) presents the prospect of developing MN patch for this drug with almost complete hoof penetration (circa 96.3% after 24h). All medicated formulations have shown similar mechanical properties after ageing for 1year under dry conditions.