RESUMO
Pregabalin and diclofenac diethylamine are anti-inflammatory molecules that are effective in relieving inflammation and pain associated with musculoskeletal disorders, arthritis, and post-traumatic pain, among others. Intravenous and oral delivery of these two molecules has their limitations. However, the transdermal route is believed to be an alternate viable option for the delivery of therapeutic molecules with desired physicochemical properties. To this end, it is vital to understand the physicochemical properties of these drugs, dosage, and strategies to enhance permeation, thereby surmounting the associated constraints and concurrently attaining a sustained release of these therapeutic molecules when administered in combination. The present work hypothesizes the enhanced permeation and sustained release of Pregabalin and diclofenac diethylamine across the skin, entrapped in the adhesive nano-organogel formulation, including permeation enhancers. The solubility studies of Pregabalin and diclofenac diethylamine in combination were performed in different permeation enhancers. Oleic acid was optimized as the best permeation enhancer based on in vitro studies. Pluronic organogel containing Pregabalin and diclofenac diethylamine with oleic acid was fabricated. Duro-Tak® (87-2196) was added to the organogel formulation as a pressure-sensitive adhesive to sustain the release profile of these two therapeutic molecules. The adhesive organogel was characterized for particle size, scanning electron microscopy, and contact angle measurement. The HPLC method developed for the quantification of the dual drug showed a retention time of 3.84 minutes and 9.69 minutes for pregabalin and diclofenac, respectively. The fabricated nanogel adhesive formulation showed the desired results with particle size and contact angle of 282 ± 57 nm and ≥120°, respectively. In vitro studies showed the percentage cumulative release of 24.90 ± 4.65% and 33.29 ± 4.81% for pregabalin and diclofenac, respectively. In order to accomplish transdermal permeation, the suggested hypothesis of fabricating PG and DEE nano-organogel in combination with permeation enhancers will be a viable drug delivery method. In comparison to a traditional gel formulation, oleic acid as a permeation enhancer increased the penetration of both PG and DEE from the organogel formulation. Notably, the studies showed that the use of pressure-sensitive adhesives enabled the sustained release of both PG and DEE.Therefore, the results anticipated the hypothesis that the transdermal delivery of adhesive PG and DEE-based nanogel across the human skin can be achieved to inhibit inflammation and pain.
RESUMO
The pervasiveness of fungal infections is an issue for skin health globally, and there are a reported 40 million cases in developed and developing countries. Novel drug delivery systems provide better therapeutic efficacy over conventional drug therapy due to their lower side effects and toxicity. Furthermore, combinations of essential oils can represent alternative therapies for fungal infections that are resistant to synthetic drugs. This study is aimed at developing Timur oil into a nanoemulgel and evaluating its antifungal effects. The development of the formulation involved the preparation of a nanoemulsion by the titration method, followed by its evaluation for various physicochemical properties. The antifungal activity of the nanoemulgel against Candida albicans was evaluated. The zone of inhibition was determined using the disk diffusion method. The results show that the developed nanoemulgel has a particle size of 139 ± 6.11 nm, a PDI of 0.309, and a zeta potential of -19.12 ± 2.73 mV. An in vitro drug release study showed a sustained release of 70 ± 0.289% of the drug over a period of 24 h. The % drug permeation across the skin was found to be 79.11 ± 0.319% over 24 h. However, the amount of drug retained in the skin was 56.45 µg/g. The flux for the nanoemulgel was found to be 94.947 µg/cm2/h, indicating a better permeability profile. The nanoemulgel formulation showed a zone of inhibition of 15 ± 2.45 mm, whereas the 1% ketoconazole cream (marketed preparation) exhibited a zone of inhibition of 13 ± 2.13 mm. The results of this study suggest that developed nanoemulgel containing Timur oil and rosemary oil has the potential to be used for treating topical fungal infections caused by Candida albicans.
