ABSTRACT
The aim of the present study was to investigate the potential of nanoemulsion formulation for topical delivery of Clobetasol propionate [CP] using algal oil [containing omega-3 fatty acids] as the oil phase. CP has anti-inflammatory, immunomodulatory and antiproliferative activities. However, its clinical use is restricted to some extent due to its poor permeability across the skin. Algal oil was used as the oil phase and was also exploited for its anti-inflammatory effect along with CP in the treatment of inflammation associated with dermatitis. Nanoemulsion formulations were prepared by aqueous phase titration method, using algal oil, tween 20, PEG 200 and water as the oil phase, surfactant, co-surfactant and aqueous phase respectively. Furthermore, different formulations were subjected to evaluate for ex-vivo permeation and in-vivo anti-inflammatory, irritation and contact dermatitis studies. The optimized nanoemulsion was converted into hydrogel-thickened nanoemulsion system [HTN] using carbopol 971 and had a viscosity of 97.57 +/- 0.04 PaS. The optimized formulation had small average diameter [120 nm] with zeta potential of -37.01 mV which indicated good long-term stability. In-vivo anti-inflammatory activity indicated 84.55% and 41.04% inhibition of inflammation for drug loaded and placebo formulations respectively. The assessment of skin permeation was done by DSC and histopathology studies which indicated changes in the structure of epidermal membrane of skin. Contact dermatitis reveals that the higher NTPDase activity in the treatment with the CP-loaded nanoemulsion could be related to the higher anti-inflammatory effect in comparison with placebo nanoemulsion gel
Subject(s)
Fatty Acids, Omega-3 , Dermatitis, Contact , Anti-Inflammatory Agents , Docosahexaenoic AcidsABSTRACT
Benign prostatic hyperplasia [BPH]is the most common condition in aging men, associated with lower urinary tract symptoms. It is caused due to the augmented levels of the androgen dihydrotestosterone. Dutasteride, a 5alpha-Reductase inhibitor has been recommended for the treatment of BPH upon oral administration. However, long term oral administration of dutasteride may cause sexual problem in man. Therefore the main objective of this study was to develop transdermal patch having nanoemulsion gel of dutasteride in order to enhance physical and chemical stability and eliminate adverse effect of dutasteride. Optimized nanoemulsion was prepared by aqueous phase-titration method and characterized by droplet size, viscosity and refractive index. In-vitro skin permeation of dutasteride through rat abdominal skin was determined by the Franz diffusion cell. Significant increase in the steady state flux [Jss], permeability coefficient [Kp] and enhancement ratio [Er] was observed in optimized nanoemulsion formulation A1 [p < 0.05]. The Er of optimized nanoemulsion A1 was found to be 1.52 times with respect to control which indicates transdermal delivery may be better approach for BPH. Stability studies were performed for the period of 3 months. It was found that droplet size, viscosity and refractive index were slightly increased at refrigerator and room temperature in 3 months period. However, the changes in these parameters were not statistically significant [p >/= 0.05]. The shelf-life of optimized nanoemulsion A1 was found to be 2.18 years at room temperature. These results indicated that both physical as well as chemical stability of dutasteride in nanoemulsion formulation