Nanoemulsion Based Hydrogel Containing Omega 3 Fatty Acids as a Surrogate of Betamethasone Dipropionate for Topical Delivery
ABSTRACT The aim of the present study was to investigate the potential of nanoemulsion formulation for topical delivery of betamethasone dipropionate (BD) using fish oil (containing omega-3 fatty acids) as the oil phase. BD has anti-inflammatory, immunomodulatory and antiproliferative activity. However, its clinical use is restricted to some extent due to its poor permeability across the skin. So to increase its permeation across the skin, nanoemulsion based gel formulations were prepared and characterised. Fish oil was used as the oil phase and was also exploited for its anti-inflammatory effect along with BD in the treatment of inflammation associated with psoriasis. Nanoemulsion formulations were prepared by aqueous phase titration method, using fish oil, Unitop 100, PEG 400 and water as the oil phase, surfactant, co-surfactant and aqueous phase respectively. Furthermore, different formulations were subjected to physical stability and consequently evaluated for ex vivo permeation and in vivo anti-inflammatory study. The optimized nanoemulsion was converted into hydrogel-thickened nanoemulsion system (HTN) using carbopol 971 and had a viscosity of 98.67 ± 0.06 PaS. The optimized formulation had small average diameter (125 nm) with zeta potential of -39 mv which indicated good long-term stability. In vivo anti-inflammatory activity indicated 87.64% and 48.76% inhibition of inflammation for drug loaded and placebo formulation respectively. Assessment of skin permeation was done by ATR-FTIR, DSC and histopathology studies which indicated changes in the structure of epidermal membrane of skin.
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ABSTRACT: Abstract Polyphenolic bioflavonoid, Rutin possesses wide range of pharmacological activities. However, it shows poor bioavailability when administered orally. The aim of this study was to formulate and compare the potential of nanoemulsions for the solubility enhancement of rutin (RU) by using different techniques. RU-loaded nanoemulsions were prepared by spontaneous emulsification method and high-pressure homogenization (HPH) technique using sefsol 218 and tocopheryl polyethylene glycol 1000 succinate (TPGS) (1:1), solutol HS15 andtranscutol P as oil phase, surfactant and co-surfactant, respectively. The prepared formulations were compared for various parameters like droplet size, percentage transmittance, zeta potential, viscosity, refractive index and in vitro release. The HPH nanoemulsions showed smaller droplet size and increased in vitro release when compared to nanoemulsions prepared by spontaneous emulsification method. The optimized formulation showed spherical globules with average globule diameter of 18 nm and zeta potential of -41 mV. Cumulative percentage drug released obtained for RU, PF6 (spontaneous emulsification formulation F6) and HF6 (HPH formulation F6) were 41.5 ± 0.04%, 49.5 ± 0.06% and 94.8 ± 0.03%, respectively, after 6 h. The permeability of RU from HF6 was found to be ≈4.6 times higher than RU suspension during ex vivo everted gut sac studies. Antioxidant activity was determined by using DPPH assay and reducing power assay method. Results showed a high scavenging efficiency toward DPPH radicals by HF6. Anti-inflammatory effect of RU as determined by carrageenan-induced rat paw edema method was found to be higher (75.2 ± 4.8%) when compared to RU suspension (46.56 ± 3.5%). It can be inferred that TPGS-loaded nanoemulsion of RU serve as an effective tool in increasing solubility and permeability of RU.Drug Delivery 03/2014; DOI:10.3109/10717544.2014.893382 · 2.20 Impact Factor
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ABSTRACT: Abstract The aim of the present study was to formulate and evaluate in situ gelling syringeable nanoemulgels (NEGs) of ketoprofen for periodontal delivery. Application of 3-factor 3-level design was employed using the Box-Behnken experimental design for the optimization of nanoemulsion using three independent variables such as percent concentration (v/v) of oil (X1), Smix (mixture of surfactant and cosurfactant) (X2) and water (X3); while the particle size (nm) (Y1), polydispersity index (Y2) and zeta potential (mV) (Y3) were used as dependent variables. The NEG was evaluated based on their drug content, pH measurement, mucoadhesion on the goat buccal mucosa, syringeability and inverted sol-gel transition temperature. The drug release data were analyzed for curve fitting based on the Korsmeyer-Peppas law, and the n-values of optimized A5 and A8 formulations were found 0.3721 and 0.3932, respectively, confirmed that both the formulations followed pseudo Fickian diffusion (n < 0.43). The formulation A8 with the optimal drug release was identified as the best NEG formulation. Results of rheological, mucoadhesion and syringeability studies showed the suitability of desired sol-gel property for periodontal drug delivery. The Herschel-Bulkley model was the best fit model to explain the flow behavior of optimized formulation. Using the HET-CAM method, significantly lower in vitro toxicity was indicated the suitability of developed NEG for intra-pocket delivery.Drug Delivery 04/2014; DOI:10.3109/10717544.2014.907842 · 2.20 Impact Factor
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ABSTRACT: Abstract Thiocolchicoside (TCC) is an effective therapeutic agent against the orthopaedic, traumatic and rheumatologic disorders but it suffer from the drawback of poor bioavailability due to extensive first pass metabolism and low permeability via the oral route. The aim of the present study was to evaluate the potential of nanoemulsion (NE) for bioavailability enhancement of TCC through the transdermal route. The NEs were developed using Linseed: sefsol in 1:1 ratio as the oil phase, span 80, Transcutol P and distilled water as surfactant, co-surfactant and aqueous phase. Furthermore, selected formulations were subjected to physical stability and consequently evaluated for in vitro permeation using porcine skin. The optimized formulation had small average globule diameter of 117 nm with polydispersity index of 0.285. The globules were spherical in shape as observed by transmission electron microscopy. The in vitro skin permeation profile of optimized NE was compared with aqueous solution of TCC. Significant increase in permeability parameters were observed in NEs formulation (p < 0.05) as compared to aqueous solution of TCC. The steady-state flux (Jss) and permeability coefficient (Kp) for optimized NE formulation (C1) were found to be 30.63 ± 4.18 µg/cm(2)/h and 15.21 × 10(-3) ± 2.81cm(2)/h, respectively. The results of enhanced permeation through transdermal route suggest that water-in-oil NEs which are compatible with the lipophilic sebum environment of the hair follicle facilitate the transport of TCC, and such transport might be predominantly transfollicular in nature. Overall, these results suggested that water-in-oil NEs are good carriers for transdermal delivery of TCC.Drug Delivery 06/2014; DOI:10.3109/10717544.2014.916764 · 2.20 Impact Factor