Self-microemulsifying drug delivery systems (SMEDDS) were developed to overcome the problems of delivery and administration of piroxicam, a drug with low bioavailability and gastrointestinal irritation, The in vitro properties of it were assessed. The solubility of piroxicam in several oils and surfactants was determined, and the compatibility of various oils and surfactants was investigated. Ternary phase diagrams were constructed to optimal area of microemulsion, and the influence of different oily phases, surfactants and co-surfactants was studied. The droplet size and dissolution of optimal formulation were determined to prove that the dosage form is a useful delivery system for piroxicam. In the optimized piroxicam SMEDDS, cinnamic alcohol was selected that gave the maximal solubility to piroxicam. Labrafil M 1944CS, Cremophor EL and Transcotol P were used as oils, surfactant and co-surfactant, respectively. Droplet size and distribution of three piroxicam SMEDDS formulations were (32.2 +/- 5.0), (40.1 +/- 6.4), (81.9 +/- 12.2) nm individually. And the releasing of piroxicam was rapid and complete. The optimized SMEDDS for piroxicam was obtained.
Administration, Oral ; Drug Compounding ; methods ; Drug Delivery Systems ; Emulsions ; Glycerides ; chemistry ; Glycerol ; analogs & derivatives ; chemistry ; Particle Size ; Piroxicam ; chemistry ; Polyethylene Glycols ; chemistry ; Propanols ; chemistry ; Solubility ; Solvents ; chemistry ; Surface-Active Agents ; chemistry

OBJECTIVE: To evaluate the effects of piroxicam patch(Trast) in rheumatoid arthritis patients with knee joint pain and swelling and to determine the concentration of plasma and synovial fluid following patch application. METHODS: Twenty-two patients with rheumatoid arthritis participated in a double-blind, placebo-controlled study. The patients were instructed to apply piroxicam or placebo patch at one knee and re-apply it every other day for 2 weeks. They had washout period for 2 weeks and then applied the other patch for 2 weeks at the same joint. The patients recorded knee joint pain using visual analog scale. Knee joint swelling and tenderness were assessed before and after application of piroxicam and placebo patch. Complete blood count, AST, ALT, BUN, creatinine, joint fluid analysis were also done. Piroxicam concentration in plasma and synovial fluid were measured by high performance liquid chromatography(HPLC) after 2 weeks of piroxicam patch application. RESULTS: Knee joint pain improved significantly after the application of piroxicam patch for 2 weeks(visual analog scale, 56. 2+5. 9m vs 48. 2+5. 7mm, p=0. 03 by Wilcoxon signed rank test). There was no significant change in white cell count of synovial fluid, peripheral blood cell count, chemistry, C-reactive protein and erythrocyte sedimentation rate. In terms of adverse effects, mild gastrointesti nal disturbance(8/21 cases, 38%) and local side effects such as pruritus and ery thema(3/21 cases, 14%) were developed, which were insignificant compared with control groups(30%, 15% respectively). Piroxicam concentrations in plasma and synovial fluid after the application of piroxicam patch were 0. 129+0. 04ug/ ml (mean+SE) and 0. 644+0. 202ug/ml respectively. CONCLUSIONS: Piroxicam patch is a safe and effective therapeutic modality for knee joint pain in patients with rheumatoid arthritis. Mild adverse effects such as gastrointestinal disturbance and local side effects were noted. Piroxicam concentration was higher in synovial fluid than in plasma following the application of piroxicam patch.
Arthritis, Rheumatoid* ; Blood Cell Count ; Blood Sedimentation ; C-Reactive Protein ; Cell Count ; Chemistry ; Creatinine ; Humans ; Joints ; Knee ; Knee Joint ; Piroxicam ; Plasma ; Pruritus ; Synovial Fluid ; Visual Analog Scale

An improved method to determine meloxicam (MEL) concentrations in koala plasma using reversed phase high performance liquid chromatography equipped with a photo diode array detector was developed and validated. A plasma sample clean-up step was carried out with hydrophilic-lipophilic copolymer solid phase extraction cartridges. MEL was separated from an endogenous interference using an isocratic mobile phase [acetonitrile and 50 mM potassium phosphate buffer (pH 2.15), 45:55 (v:v)] on a Nova-Pak C18 4-microm (300 x 3.9 mm) column. Retention times for MEL and piroxicam were 8.03 and 5.56 min, respectively. Peak area ratios of MEL to the internal standard (IS) were used for regression analysis of the calibration curve, which was linear from 10 to 1,000 ng/mL (r2 > 0.9998). Average absolute recovery rates were 91% and 96% for MEL and the IS, respectively. This method had sufficient sensitivity (lower quantitation limit of 10 ng/mL), precision, accuracy, and selectivity for routine analysis of MEL in koala plasma using 250-microL sample volumes. Our technique clearly resolved the MEL peak from the complex koala plasma matrix and accurately measured MEL concentrations in small plasma volumes.
Animals ; Anti-Inflammatory Agents, Non-Steroidal/*blood ; Chromatography, High Pressure Liquid/methods/*veterinary ; Molecular Structure ; Phascolarctidae/*blood ; Piroxicam/chemistry ; Quality Control ; Reproducibility of Results ; Sensitivity and Specificity ; Thiazines/*blood ; Thiazoles/*blood

An improved method to determine meloxicam (MEL) concentrations in koala plasma using reversed phase high performance liquid chromatography equipped with a photo diode array detector was developed and validated. A plasma sample clean-up step was carried out with hydrophilic-lipophilic copolymer solid phase extraction cartridges. MEL was separated from an endogenous interference using an isocratic mobile phase [acetonitrile and 50 mM potassium phosphate buffer (pH 2.15), 45:55 (v:v)] on a Nova-Pak C18 4-microm (300 x 3.9 mm) column. Retention times for MEL and piroxicam were 8.03 and 5.56 min, respectively. Peak area ratios of MEL to the internal standard (IS) were used for regression analysis of the calibration curve, which was linear from 10 to 1,000 ng/mL (r2 > 0.9998). Average absolute recovery rates were 91% and 96% for MEL and the IS, respectively. This method had sufficient sensitivity (lower quantitation limit of 10 ng/mL), precision, accuracy, and selectivity for routine analysis of MEL in koala plasma using 250-microL sample volumes. Our technique clearly resolved the MEL peak from the complex koala plasma matrix and accurately measured MEL concentrations in small plasma volumes.
Animals ; Anti-Inflammatory Agents, Non-Steroidal/*blood ; Chromatography, High Pressure Liquid/methods/*veterinary ; Molecular Structure ; Phascolarctidae/*blood ; Piroxicam/chemistry ; Quality Control ; Reproducibility of Results ; Sensitivity and Specificity ; Thiazines/*blood ; Thiazoles/*blood