Dissolving Polymeric Microneedles for Enhanced Transdermal Drug Delivery: Formulation Optimization, Characterization, and Permeation Studies

Abstract

This investigation aimed to fabricate and optimize dissolving microneedle patches composed of hydroxypropyl methylcellulose and polyvinylpyrrolidone for transdermal delivery of two model drugs: berberine chloride (BBR) and salmon calcitonin (sCT). Dissolving microneedles were prepared using the micromolding technique. The effects of polymer type, concentration, polymer blending ratios, and vacuum-assisted air bubble removal duration on microneedle morphology, mechanical strength, and rheological behavior were investigated. In vitro drug permeation and skin retention were evaluated using vertical diffusion cells with excised mouse skin. A vacuum duration of 15 min × 2 cycles was optimal for complete air removal from the polymeric solution. Among the four polymers screened, HPMC E3 and PVP K10 yielded microneedles with superior morphology, greater needle lengths, and lower percentage length reduction upon compression. All polymer solutions displayed pseudoplastic flow behavior, and viscosity decreased with increasing temperature. Two optimized formulations were selected: MN6.3 (HPMC E3 10%/PVP K10 30%) and MN7.2 (HPMC E3 20%/PVP K10 20%). In vitro permeation studies revealed that MN7.2 released 49.45 ± 3.82% of BBR and 16.16 ± 0.48% of sCT through mouse skin over 24 h, substantially higher than the corresponding control patches (39.80 ± 4.70% and 9.26 ± 0.55%, respectively, n = 4, p < 0.05). Drug loading, transdermal permeation, percentage of drug released, lag time, steady-state flux, and drug quantity in skin were reported and compared among the groups. Conclusively, HPMC E3/PVP K10 dissolving microneedles represent a promising platform for enhancing transdermal delivery of drugs spanning a wide molecular weight range, from small hydrophilic alkaloids to large peptides.