Formulation development and evaluation of methimazole microemulsion gel for topical skin application

The aim of this study was to develop and optimize a topical methimazole microemulsion gel (MEGL) formulation to enhance the drug’s skin penetration and retention whilst minimizing systemic side effects. Microemulsions were prepared using oleic acid, Transcutol P, Span 20, Tween 80, propylene glycol, and purified water, and incorporated into a gel matrix composed of poloxamer 407 and carbomer 980 to produce five MEGL formulations. The zeta potential, polydispersity index, droplet size, and pH of the microemulsions were characterized, and the MEGL formulations were systematically evaluated for appearance, apparent viscosity, spreadability, crystallization, drug content, intratube uniformity, pH, impurities, in vitro release, and in vitro permeation. All microemulsion batches exhibit excellent properties, including nanoscale droplet size (~ 38–43 nm), a narrow polydispersity index (< 0.35), a high negative zeta potential (~ –40 mV), and a slightly acidic pH (4.5–4.6). The results indicated that all microemulsion batches exhibited excellent physical stability, with a zeta potential of approximately − 40 mV and droplet sizes ranging from 38 to 43 nm. The MEGL formulations presented as white, smooth gels with no crystal formation; drug content was close to the theoretical value (99.2%–100%), and the impurity profile was low (total impurities 0.09%). In vitro release studies showed that MEGL02 (P407 5%, C980 0.75%) exhibited sustained-release characteristics, with a cumulative release rate of 99.2% over 24 h; the release kinetics conformed to first-order. In vitro penetration studies indicated that MEGL02 achieved the highest skin retention rate (68.43%) and the lowest skin penetration rate (0.23%), outperforming other formulations. This research successfully developed a stable, controlled-release formulation that increased local skin retention while minimizing systemic exposure. This developed formulation could be further evaluated for an in vivo study for the treatment of melasma.