Mirtazapine Loaded NLCs‑Based Hydrogel for Topical Delivery in Pruritus: Statistical Optimization, In vitro and Skin Irritation Evaluation.

Abstract

Systemic mirtazapine (MRT) delivery for the treatment of pruritus exhibits severe side effects which needs to be addressed. For this purpose, topical nanostructured lipid carriers (NLCs) containing MRT were developed to minimize side effects and enhance therapeutic efficacy. The microemulsion method was utilized for the preparation of MRT loaded NLCs and the final optimized formulation was loaded in the gel for effective topical application. The formulation was optimized in terms of particle size (PS), zeta potential (ZP), polydispersity index (PDI), and percentage entrapment efficiency (% EE) by keeping in view the quantity of drug, tween 80 and lipids ratio. Optimized nano formulation exhibited the PS of 186.3 ± 1.2 nm, with 0.217 ± 0.03 PDI, ZP of -26.0 ± 0.2 mV and %EE of 86.3 ± 0.3%. Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) analysis confirmed the compatibility of components of nano formulation and encapsulation of drug inside lipid matrix, respectively. Further, the gel-based optimized MRT-loaded NLCs dispersion was analyzed for rheology and textural characterization. The prepared hydrogel (MRT-loaded NLCs gel) had a transparent appearance, non-gritty texture, pH, and spreadability of 322.33 ± 0.25%, respectively. MRT loaded NLCs gel exhibited a drug release of 81% in 24 h and followed Korsmeyer-Peppas model. Ex vivo skin permeation depicted only 6.20 µg/cm² drug permeation across the skin after 24 h. Skin irritation study showed no signs of erythema and edema in nano formulation-treated group. MRT-loaded NLCs gel was formulated successfully and may be used as a promising vehicle for topical delivery of pruritus.