Transmucosal Permeation of Topically Applied Diclofenac and Piroxicam

Objectives: Topical NSAIDs applied to mucous membranes may be useful for a variety of conditions ranging from pain to inflammation. Because human vaginal mucosa can be used as a substitute for buccal mucosa for in vitro permeability studies, this model was utilised to study the transmucosal permeation kinetics of diclofenac and piroxicam from topically applied solutions and gels. Methods: Human vaginal mucosa (snap-frozen in liquid N2, stored at -85°C) was used for all permeability experiments. Permeation of diclofenac and piroxicam (ex solutions and gels) through the above mucosa was determined using a flow-through diffusion system (20°C, 24h) and high-pressure liquid chromatography. An ANOVA and a Duncan’s multiple range test were used for determining steady state flux conditions and an unpaired t test with Welch’s correction for comparing differences between the mean flux values at each 2h time point. Results: Flux rates of both diclofenac and piroxicam from aqueous solutions were significantly (p<0.05) higher than those from the gels. Steady state flux rates of the 5mg/ml diclofenac solution were approximately half those of the 10mg/ml solution. Maximal partitioning to the mucosa from the aqueous solutions and/or saturable diffusion kinetics was achieved at concentrations of £ 5mg/ml for the piroxicam under the experimental conditions used. Conclusions: The permeation of diclofenac and piroxicam through mucosa appears to be more efficacious when aqueous solutions, rather than gel formulations, of these two compounds are used. This must be borne in mind when vehicles for both these NSAIDs are selected for intraoral application. There also appeared to be a limit to the release-rate of piroxicam from the aqueous solutions and/or its flux rate across mucosal tissues.