Formulation of Microemulsion-Based Gels for Enhanced Topical Administration of Nonsteroidal Anti-Inflammatory Drugs

Nonsteroidal anti-inflammatory drugs are commonly administered orally to manage pain and inflammation, but they can have negative gastrointestinal side effects. Topical delivery is an alternative, and microemulsions (μEs) have been shown to be effective in facilitating, but they suffer from a liquid nature and low long-term retention on the skin. Hence, microemulsified gels (μEGs) have been developed, and in this study, we explored certain μEGs with diclofenac sodium (DF-Na) and naproxen sodium (NP-Na) with the hypothesis to ensure a slower and more sustained delivery of NSAIDs through the skin. The μEGs comprised castor oil (∼8%), water (∼12%), Tween-20 (∼72%), Span-20 (∼8%), poloxamer 407, and DF-Na or NP-Na. Optical microscopy was used to study the microstructures in the μEs and μEGs, and phase transitions from water-in-oil (w/o) to oil-in-water (o/w) with continuous networks were observed. Based on studies with dynamic light scattering and analyses of electron micrographs, it was observed that the μEs and μEGs loaded with DF-Na and NP-Na comprised monomodal nanodroplets. The average sizes of the droplets were (∼35 nm) and (∼60 nm) for the μEGs, without and with drugs. Fluorescence spectroscopy was used to ensure that the drugs were more likely to be present in the hydrophobic microenvironment of the formulations. Moreover, ex vivo permeation studies were conducted at pH values of 5.5 and 7.4 across rabbit skin. The release rates of DF-Na (>99 ± 1.5%,