Development and evaluation of ibuprofen loaded mixed micelles preparations for topical delivery

Abstract

In this study, novel ibuprofen-loaded mixed micelles (MMs) formulation and mixed micelles-based Carbopol gel (MMs-Gel) were prepared for topical delivery of ibuprofen. The MMs were optimized using central composite design (CCD) with entrapment efficiency (EE %) and drug loading (DL %) as indicators and characterized for morphology, size, zeta potential and critical micelle concentration (CMC). Subsequently, the optimal MMs were incorporated into Carbopol 940 gel. The novel formulations were evaluated for ex vivo permeation study, skin irritation, pharmacodynamics study and histopathology study. The optimal MMs were found to be round-shapes having nanosized diameter with negative charges, and small CMC. In ex vivo permeation study, MMs, MMs-Gel (5:1, v/v) and marketed product showed significant skin permeation with similar cumulative amounts (Q24). Skin irritation study demonstrated MMs and MMs-Gel formulations showed significant safety compared to the marketed product. Also, the developed formulations exhibited desirable anti-inflammatory activity. The histopathology study elucidated that the optimal MMs and MMs-Gel formulations could disturb the tightly conjugated keratinocyte layer. All the results suggested that the MMs and MMs-Gel would guarantee the safety and efficacy for topical delivery of ibuprofen.