Formulation\nof Microemulsion-Based Gels for Enhanced\nTopical Administration of Nonsteroidal Anti-Inflammatory Drugs

Nonsteroidal anti-inflammatory drugs are commonly administered\norally to manage pain and inflammation, but they can have negative\ngastrointestinal side effects. Topical delivery is an alternative,\nand microemulsions (μEs) have been shown to be effective in\nfacilitating, but they suffer from a liquid nature and low long-term\nretention on the skin. Hence, microemulsified gels (μEGs) have\nbeen developed, and in this study, we explored certain μEGs\nwith diclofenac sodium (DF-Na) and naproxen sodium (NP-Na) with the\nhypothesis to ensure a slower and more sustained delivery of NSAIDs\nthrough the skin. The μEGs comprised castor oil (∼8%),\nwater (∼12%), Tween-20 (∼72%), Span-20 (∼8%),\npoloxamer 407, and DF-Na or NP-Na. Optical microscopy was used to\nstudy the microstructures in the μEs and μEGs, and phase\ntransitions from water-in-oil (w/o) to oil-in-water (o/w) with continuous\nnetworks were observed. Based on studies with dynamic light scattering\nand analyses of electron micrographs, it was observed that the μEs\nand μEGs loaded with DF-Na and NP-Na comprised monomodal nanodroplets.\nThe average sizes of the droplets were (∼35 nm) and (∼60\nnm) for the μEGs, without and with drugs. Fluorescence spectroscopy\nwas used to ensure that the drugs were more likely to be present in\nthe hydrophobic microenvironment of the formulations. Moreover, ex\nvivo permeation studies were conducted at pH values of 5.5 and 7.4\nacross rabbit skin. The release rates of DF-Na (>99 ± 1.5%, <i>P</i> < 0.07) and NP-Na (>89 ± 1.1%, <i>P</i> < 0.01) were slower for the μEGs within 8–10 h than\nfor the μEs at the low pH, which is of relevance to the optimal\npH of the skin. It was observed that μEGs with high viscosities\nare effective and may have potential for use in topical drug delivery\napplications.