Formulation and Evaluation of Microemulsion-based Transdermal Delivery of Duloxetine Hydrochloride

Abstract

Duloxetine Hydrochloride (DH), is a selective serotonin and nor-adrenaline reuptake inhibitor, used in the treatment of depression, diabetic peripheral neuropathic pain and moderate to severe stress urinary incontinence in women. It has high first-pass metabolism and undergoes degradation in acidic environment, leads to poor oral bioavailability. Here, we sought to develop as microemulsion (ME) based transdermal drug delivery for enhanced bioavailability of DH. The components and concentration ranges of DH-ME were selected, using constructed pseudo-ternary phase diagram. Optimized DH-ME formulation was selected based on physico-chemical properties, stability studies and in vitro drug release. Further, the optimized DH-ME converted to gel (DH-ME-G) by the addition of Carbopol 934 as gelling agent. DH-ME-G was evaluated for pH, viscosity, appearance and drug content. In vitro drug release and ex vivo permeation of DH-ME-G were performed through dialysis membrane and rat skin, using diffusion method. DSC and FTIR studies revealed no interaction of drug and excipients. Based on drug release, size, PDI, and zeta potential (ZP) F13 formulation was selected as the optimized formulation, which contain 20 mg of DH, 15.3% of Capmul MCM (oil) and 35.7% of Smix (Labrasol: Transcutol P), 48.8% of water.  It had a droplet size of 65.8 ± 3.1nm, PDI of 0.19 ± 0.08, ZP of + 44.8 ± 3.0 mV and drug content of 97.3 ± 2.6 % with drug release of 98% in 24 h. DH-ME-G showed 97.5 ± 3.1 % drug content, in vitro and ex vivo drug permeation of 72 and 51%, respectively in 24 h. Therefore, these results conclusively demonstrated the DH-ME and DH-ME-G as an alternative delivery system for transdermal delivery of DH.