Hydrogel-thickened nanoemulsions for topical administration of ibuprofen

Abstract

Although oral ibuprofen is effective in of acute and chronic pain, its use carries a risk of serious adverse effects. The present work was aimed at developing pharmaceutically optimized topical hydrogel thickened nanoemulsions of ibuprofen for treating musculoskeletal pain. Nanoemulsions offer the advantage of increasing solubility and delivery of active agents through their skin permeation enhancing effect. The solubility of ibuprofen in various oils (including isopropyl myristate, isopropyl palmitate and ethyl oleate), surfactants and co-surfactants was determined. In order to determine the existence range of nanoemulsions, pseudo-ternary phase diagrams were constructed using the aqueous titration method. After equilibration, the mixtures were assessed visually and determined as being nanoemulsions, crude emulsions or gels. Ibuprofen was dissolved in the oil, surfactant, and co-surfactant and then an appropriate amount of water was added to the mixture with continuous stirring. Carbopol 971 was slowly mixed with the nanoemulsion under stirring. Evaluation of hydrogel-based nanoemulsion for parameters like droplet size analysis and morphology, in vitro permeation, skin accumulation and histology were conducted. The anti-inflammatory activity of the pharmaceutically optimized dosage form was evaluated by carageenan induced rat paw edema. Stability of the dosage form was established at room temperature (25 deg C/60% RH) for 12 months and accelerated (40 deg C/75% RH) conditions stability for 6 months, as per the ICH guidelines. Ibuprofen hydrogel-thickened nanoemulsion with isopropyl myristate showed a higher ex-vivo permeation rate when compared with ethyl oleate. Skin histopathology studies showed no significant findings. The optimized formulation showed higher flux of ibuprofen and a greater anti-inflammatory effect. A pharmaceutically optimized non-greasy nanoemulsion of ibuprofen for topical administration provided robust and long lasting effects. Human studies are needed to evaluate the clinical effects of the nanogel dosage forms. Supported by a grant from Relmada Therapeutics, Inc.