Design of solid lipid nanoparticles of the NSAID dexflurbiprofen for topical delivery

Abstract

The objective of this study was to develop solid lipid nanoparticle (SLN) topical gels of dexflurbiprofen, the active enantiomer of the NSAID fluribiprofen. Solid lipid nanoparticles (SLNs) are non-irritant and non-toxic, and accumulate the drug in the skin layers, hence well suited for use on local pain relief. Topical SLNs modulate drug release into the skin and improve delivery to dermal layers. SLNs bearing dexflurbiprofen could potentially manage loco-regional pain, stiffness and/or inflammation in musculoskeletal disorders such as osteoarthritis, rheumatoid arthritis and low back pain. A variety of SLNs were fabricated using stearic acid and cholesterol as lipids, with poloxamer F68, Span 80 and soya lecithin as surfactants. The SLNs were evaluated for particle size distribution, shape, rheology and percent drug entrapment. SLN enriched gels were evaluated for dexflurbiprofen content. Stability of pharmaceutically optimized SLNs 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. Optimized SLNs had an average particle size of 437 nm. Shape and morphology revealed that the particles were spherical in shape. Percent entrapment of the drug was determined using UV method and was found to be 89±4%. Ex vivo diffusion was carried out using Franz Diffusion cells. Drug accumulation and histopathological studies were carried out. The highest accumulation of dexflurbiprofen was seen from Carbopol 940 gels. Histological studies indicated that there were no abnormalities on skin layers treated with developed gel formulations. In vivo efficacy and safety of the optimized formulation was determined using carrageenan induced rat paw edema method, hot plate analgesiometer and dermal irritancy test. The results of present study suggest the potential of solid lipid nanoparticles for topical delivery of dexflurbiprofen. Supported by a grant from Relmada Therapeutics, Inc. The objective of this study was to develop solid lipid nanoparticle (SLN) topical gels of dexflurbiprofen, the active enantiomer of the NSAID fluribiprofen. Solid lipid nanoparticles (SLNs) are non-irritant and non-toxic, and accumulate the drug in the skin layers, hence well suited for use on local pain relief. Topical SLNs modulate drug release into the skin and improve delivery to dermal layers. SLNs bearing dexflurbiprofen could potentially manage loco-regional pain, stiffness and/or inflammation in musculoskeletal disorders such as osteoarthritis, rheumatoid arthritis and low back pain. A variety of SLNs were fabricated using stearic acid and cholesterol as lipids, with poloxamer F68, Span 80 and soya lecithin as surfactants. The SLNs were evaluated for particle size distribution, shape, rheology and percent drug entrapment. SLN enriched gels were evaluated for dexflurbiprofen content. Stability of pharmaceutically optimized SLNs 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. Optimized SLNs had an average particle size of 437 nm. Shape and morphology revealed that the particles were spherical in shape. Percent entrapment of the drug was determined using UV method and was found to be 89±4%. Ex vivo diffusion was carried out using Franz Diffusion cells. Drug accumulation and histopathological studies were carried out. The highest accumulation of dexflurbiprofen was seen from Carbopol 940 gels. Histological studies indicated that there were no abnormalities on skin layers treated with developed gel formulations. In vivo efficacy and safety of the optimized formulation was determined using carrageenan induced rat paw edema method, hot plate analgesiometer and dermal irritancy test. The results of present study suggest the potential of solid lipid nanoparticles for topical delivery of dexflurbiprofen. Supported by a grant from Relmada Therapeutics, Inc.