Piroxicam Percutaneous Patch

Piroxicam, one of inhibitors of biosynthesis of PG[1], was widely used for the treatment of rheumatic arthritis and rheumatoid arthritis in clinics. It has the special properties of low dose, long half-life, no accumulation and assured effects. But it may bring up adverse effects on gastrointestinal tract when orally administrated. Even bleeding and ulceration often occur. There are several kinds of dosage forms marketed such as tablet, injection and topical gel. In order to avoid its adverse effect by oral administration and be administrated conveniently, the topical patch of piroxicam was formulated and studied.First, basic physical-chemical properties of drug were investigated. The results showed that piroxicam belonged to lipophilic drug and was suitable to applied topically . Horizontal diffusion cell was used to screen the permeation promoters in order to improve the drug permeation. In vitro permeation experiments showed that the permeation kinetics of piroxicam across the rat skin was zero order with a steady-state flux (Js) of 1.38 0.26 10-3 g/cm2/s and permeability coefficient of 0.79 0.15 10-6cm/s. the co-application of enhancers could increase the permeability of the drug with enhancement ratios>l. Js of piroxicam treated with 3%Azone was increased to 11.19 1.58 g/cm2/s, which is significantly different from the control (P<0.001), ER is 8.11 and Lag time was shortened to 0.89 0.76h.The DSC and TG methods were used to study the properties of drug and excipients. The experimental results showed that drug and excipients were stable and they were compatible with each other. The method of evaporating organic solvent was established to prepare piroxicam patch with acrylate PSA as vehicle. Optimal formulation was acquired by orthogonal experiment. The fact that adhesion of patch was ideal was demonstrated by adhesion experiment. The stability experiments showed that piroxicam patches were stable. The patches almost having no irritation was proved by irritation experiments.In order to observe the advantages of the peimeation routes oftopically applied drug, to study the effect of subcutaneous microvessles and to compare the topical and oral delivery of piroxicam, drug disposition in local deep tissues (skin, muscle and joint) and plasma was investigated after oral and topical application. The plasma Cmax and AUCplasma p. o were 71.6 31.08 g/ml, 663.3 g/ml-h respectively. In comparison, the plasma Cmax and AUCpiasma were 2.12+0.38P g/ml and 65.5 g/ml-h respectively by topical application. However, by oral application, the Cmax and AUCmuseie for local muscle were 4.61 1.90 g/ml, 71.5 g/ml-h respectively in comparison with muscle Cmax 5.78 3.40 g/ml and AUCmuscle149.62 g/ml-h after local application. The results indicated that most piroxicam arrived at deeper local tissues resulted from direct permeation and subcutaneous microvessles is not always a infinite "sink" and can deliver topically applied drug to local deeper tissues, transdermal delivery of piroxicam was superior to the oral administration to achieve high drug concentration in local deep tissues while avoiding high plasma concentration and reducing side effects.The human pharmacokinetic parameters were acquired after topical application of piroxicam patch. Tmax, Cmax and AUCplasma were 8h, 18.28ng/m and 516.45ng/ml-h respectively, there were average total amount 13.87 2.87mg drug delivered to each man. The experimental results suggest that little amount of drug entered into circulation system and most drug accumulated in the skin and local deeper tissues of dosed sites.