Meloxicam Patch

Meloxicam is a new NSAID. In contrast with other NSAIDs currently available,it appears to have greater inhibitory activity against the inducible isoform of cyclo-oxygenase(COX-2), which is implicated in the inflammatory response, than against the constitutive isoform (COX-1),inhibition of which is associated with gastrointestinal and renal adverse events and inhibition of platelet aggregation. However, it was reported recently that the COX-2inhibitor could cause the danger renal harm because of its important actor in regulating and controlling the renal function. In order to adapt the need of large amount of rheumatoid arthritis and ostoarthritis patients with renal and gastrointestinal suffer, the Meloxicam transdermal film was formulated and studied.The PBS with pH8 was used as permeation medium. The enhancement of ten kinds of permeation enhancers for Meloxicam across full thickness rat skin was studied with modified Valia-Chien diffusion cell. And the steady-state fluxes (Js) and enhancement ratios (ER) for Meloxicam through the rat skin being treated by variable enhancers were compared with control. It was indicated that the enhancement effects of the oil-soluble enhancers were not more significant than water-soluble ones, while their lag time was longer than the later. The synergistic effect between Azone and propylene glycol (PG) were confirmed by comparing the enhancement of Azone using PG as solvent with using ethanol. The enhancements of Azone and Menthe oil were also studied with ethanol as solvent and found to be dependent on the concentration of the enhancers. Cutaneous microdialysis technique was applied to study the enhancements of Azoneand Menthe Oil for the permeation of meloxicam across the skin of rat in vivo. On the same time a sensitive HPLC method was developed and used to determine meloxicam in the dialysate. A good relationship was found in the study for permeability of meloxicam between the method of diffusion cell, which is used to study the permeation of meloxicam across the full excised rat skin, and microdialysis technique.The methodology for determination the quality of meloxicam patch such as adhesion, content , release and permeation, etc., were studied first. The DSC and TG technique were used to study the contraindication between the drug and excipients and it is showed they were compatible with each other. With acrylic polymers E100 as adhesive vehicle, the formulation and procedure of meloxicam patch was studied. Optimal formulation was achieved by orthogonal experiment with the permeability of the drug across the excised hairless mouse skin and adhesion of the patch as index of the optimization. It was showed that the permeation kinetics of meloxicam across the hairless mouse skin belonged to zero-order pattern.After topical administration of the patch, drug disposition in local deep tissues (skin, muscle) and plasma was investigated with HPLC technique, and the examination was implemented simultaneously following oral administration. The Cmax and AUC in plasma p.o. were found more higher than topical administration. However, the Cmax and AUC in skin and muscle p.o were more lower than topical administration, which showed that topical administration of meloxicam was superior to the oral administration in achieving higher drug concentration in local deep tissues, avoiding high plasma concentration and reducing side effects.On the other hand , cutaneous microdialysis technique was used tostudy the drug delivery across the hairless skin invo after the administration of meloxicam patch. It was demonstrated that the free drug concentration in dermis determined by microdialysis was far lower than the total concentration in skin and muscle found by biopsy, which suggested that there could be a high protein bound ratio in skin following topical administration.