Design, Optimization and Characterization of Combined Ethosomal Transdermal Patch of Glimepiride and Duloxetine Drug Regimen for Diabetes and Associated Neuropathic Pain Management

Abstract

Background: Diabetic neuropathic pain is the most prevalent type of neuropathic pain and a major consequence of diabetes. A wide range of medications, whether administered alone or in combination, have been found to dramatically decrease neuropathic pain. Objective: This study aimed to develop the glimepiride (GLM) and duloxetine (DUL) ethosomal transdermal drug delivery patches to prolong and improve the discharge of the drug regimen to treat diabetics as well as neuropathic pain associated with it. Methods: Using the solvent casting method, DUL and GLM ethosomal dispersions were formulated by a 32 factorial design. A total of nine formulations were developed considering ethanol (X1) and phospholipid (X2) independent factors, and the formulation was optimized based on entrapment efficiency (Y1) and particle size (Y2). Moreover, size, surface charge, and % entrapment efficiency were characterized. The ethosomal formulations converted into patches were characterized by thickness, folding endurance, in vitro penetrability, and ex vivo skin permeability. Results: The results of thickness, % moisture content, % moisture uptake, and folding endurance were in an acceptable range for all formulations. Based on the in vitro penetrability and ex vivo skin permeability profile, formulation F9 was considered optimized, extending the cumulative drug release of more than 60 % up to 24hrs and skin permeability of more than 200 μg/cm2. Conclusion: The investigation showed that the medication increment transdermal fix of GLM and DUL was a promising path for the therapeutic management of diabetes and diabetic neuropathic pain.