Pharmacokinetics of meloxicam in skin by microdialysis technique in a rabbit model

Meloxicam is a non steroidal anti-inflammatory drug (NSAID) that exhibits anti-inflammatory, analgesic and antipyretic activity. The oral dosage form of NSAID's produce severe gastric adverse reactions, hence topical dosage form have advantages over oral dosage form. About 42 million Americans have arthritis, which generally occurs after age of 65 year. In arthritis prostaglandins are found at elevated levels at the joints. Meloxicam inhibits an enzyme cyclooxygenase which makes prostaglandins.;Microdialysis is a highly reproducible and semi invasive method that allows to determine the drug concentration in the tissue. Recovery shows the relationship between concentration of analyte in tissue and those in dialysate samples. In-Vivo recovery cannot be estimated directly, hence retrodialysis method was chosen for probe calibration. Training and skill is requiring for microdialysis but still it provides highly dynamic continuous sampling and monitoring for several hours. The dialysate sample volume is very low so needed very sensitive analytical method for drug analysis.;To determine meloxicam in dialysate samples High Performance Liquid Chromatography (HPLC) method has been used. To analyze the meloxicam flow rate of 1 mL/min, detection wavelength of 370 nm and C18 column was used. Mobile phase consisted of Methanol, Water and Phosphoric acid (69.9:30:0.1). The retention time reported was 2.7 to 3.3 min. The calibration curves for microdialysis samples were linear in the range of 10--10,000 ng/mL with a correlation coefficient larger than 0.99. The lower limit of quantification was 10 ng/mL for microdialysis samples.;The rabbit was chosen for the In-Vivo pharmacokinetic study of meloxicam. 4 female pathogen free New Zealand albino rabbits were used. Rabbits were tranquilized with Acipromazine maleate with a dose of 5 mg/Kg by Intra muscular route of administration. Microdialysis probes were inserted using sterile needle specific for microdialysis. The retrodialysis was done by using 10000 ng/mL meloxicam solutions as perfusate. In recovery studies 0.07 g meloxicam gel with and without penetration enhancer was applied on 1 x 1 cm2 area and ringer lactate's solution was used as perfusate.;The result of this study shows that there was no statistically significant differences were found between the formulations and apparently no effect of permeation enhancer was observed. Dermis concentration then decreased by 40% and steady state was reached. The results may be explained by duration of experiment, increase in dermis concentration and capacity limited behavior of probe. Further studies need to be conducted to test these hypotheses.