Testing Topical Products Specifically to Reduce Inflammatory Pain from Gout: Transdermal NSAID Delivery and Monosodium Urate Solubility

Abstract

Gout is caused by crystals of monosodium urate (MSU) in the joints. Topical nonsteroidal antiinflammatory drug products (NSAIDs) are often the first-choice immediate treatment. This study examined the effect of commercially available and newly developed transdermal NSAID products on the solubility of MSU in a physiologically relevant system, alongside the efficacy of transdermal NSAID delivery. Materials and Methods: Drug permeability of 7 commercially available topical NSAID products, alongside 3 newly developed "Gout Buster" products, was evaluated in vitro using pig's ear skin in Franz diffusion cells. The standard Franz cell experimental protocol was adapted to include assessment of MSU solubility in phosphate buffered saline for each product. Some materials were also tested via direct solubility studies. Results: The amount of drug delivered transdermally varied significantly between different formulations, with the best ibuprofen delivery being ~5 times higher than the lowest, and best diclofenac delivery being ~3.5 times higher than the lowest. Changes in formulations and the drug concentration in the product both affected the amount of drug delivered. Overall ibuprofen permeation was higher than diclofenac. The commercially available products showed little or no effect on the MSU solubility (99-103% vs control). The Gout Buster products showed significant improvement in the MSU solubility after permeation through skin (120-126%). Increased sodium levels reduced the solubility of MSU in direct solubility studies. Conclusion: In these trials, the Gout Buster products showed significantly improved permeation of both ibuprofen and diclofenac over the commercial products at similar drug concentrations, and showed significant improvement for MSU solubility. Increased sodium levels reduced the solubility of MSU and could cause more crystallisation in vivo. Therefore, topical NSAID products with the Gout Buster formulation may have the best likelihood of both reducing inflammation and helping re-dissolve the MSU crystals that cause gout.