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 (mu Es) 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 (mu EGs) have been developed, and in this study, we explored certain mu EGs 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 mu EGs comprised castor oil (similar to 8%), water (similar to 12%), Tween-20 (similar to 72%), Span-20 (similar to 8%), poloxamer 407, and DF-Na or NP-Na. Optical microscopy was used to study the microstructures in the mu Es and mu EGs, 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 mu Es and mu EGs loaded with DF-Na and NP-Na comprised monomodal nanodroplets. The average sizes of the droplets were (similar to 35 nm) and (similar to 60 nm) for the mu EGs, 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%, P < 0.07) and NP-Na (>89 +/- 1.1%, P < 0.01) were slower for the mu EGs within 8-10 h than for the mu Es at the low pH, which is of relevance to the optimal pH of the skin. It was observed that mu EGs with high viscosities are effective and may have potential for use in topical drug delivery applications.