Transdermal Delivery of Ketorolac Tromethamine Using Microemulsion Vehicles

Abstract

Background: Ketorolac tromethamine (KT) is described as a nonsteroidal anti-inflammatory drug (NSAID). Among various NSAIDs, ketorolac tromethamine is commonly used for postoperative and emergency relief of pain. Objectives: The goal of this study was to describe and assess the in vitro skin permeability of KT microemulsions (MEs). Methods: The KT ME formulations were prepared using pseudoternary phase diagrams. Appropriate ratios of oil, S/C mixture, and water were selected, and eight formulations were prepared based on a full factorial design consisting of three variables at two levels. The droplet size, differential scanning calorimetry, pH, stability, viscosity, drug release, and skin permeability were examined in the prepared MEs. Results: The droplet size of ME samples ranged from 28.36 to 81.4 nm, and pH was within the range of 5.1 - 5.7. In addition, the viscosity of MEs was 38 - 135 cps. Considering the drug release profile, 88.04% of the drug (ME-K-1) was released within 24 hours. All ME formulations drastically increased the permeability coefficient and flux in the rat skin. The Jss and Papp parameters were 0.144 mg/cm2.h and 0.0057 cm2/h in the ME-K-8 formulation, respectively (i.e., 8.42 and 8.41 times higher than the control, respectively). Based on the findings, they were visually cleared, and no phase separation was detected. Conclusions: According to the findings, the oil, S/C mixture, and water contents in ME formulations affect physicochemical characteristics and permeation parameters. The selected MEs increased the rate of permeation and permeability coefficient through rat skin. Ideally, MEs should transfer the drug through the skin while maintaining its size and release it into deep layers of the skin. ME formulations may be proper carriers for transdermal ketorolac delivery, although further research is necessary to validate their therapeutic application.