Piroxicam Benzoate-Synthesis, HPLC Determination, and Hydrolysis

• Published in: Drug development and industrial pharmacy 2003-01, Vol.29 (2), p.155-160
• Main Authors: Boneschans, Barend, Wessels, Anita, van Staden, Johan, Zovko, Marijana, Zorc, Branka, Bergh, Jacobus
• Format: Article
• Language: English
• Subjects: Benzoates - chemical synthesis; Benzoates - chemistry; Biological and medical sciences; Bones, joints and connective tissue. Antiinflammatory agents; Buffers; Chromatography, High Pressure Liquid; HPLC; Hydrolysis; Kinetics; Medical sciences; Pharmaceutical Solutions; Pharmacology. Drug treatments; Piroxicam; Piroxicam - analogs & derivatives; Piroxicam - analysis; Piroxicam - chemical synthesis; Piroxicam - chemistry; Piroxicam benzoate; Powders; Reproducibility of Results; Sensitivity and Specificity; Solubility; Time Factors; Validation
• ISSN: 0363-9045; 1520-5762
• DOI: 10.1081/DDC-120016723

Abstract An improved method of piroxicam benzoate synthesis was described, and an isocratic reversed-phase high-performance liquid chromatography method for its determination was developed and fully validated. The method was found to be specific, precise (relative standard deviation 0.3%), accurate (mean recovery 99.9%), and robust. Limit of detection was estimated at 0.055 µg mL−1 and limit of quantification at 0.185 µg mL−1. The kinetics of piroxicam benzoate hydrolysis in aqueous buffer solutions (pH 1.1 and 10), simulated gastric and intestinal fluids was studied. The hydrolysis followed first-order kinetics. The following rate constants were obtained at pH 10: k = 1.8 × 10−3 hr−1 at 37°C and k = 3.4 × 10−2 hr−1 at 60°C. In acidic media, no significant hydrolysis was observed after 24 hr. During the 24-hr period in simulated intestinal fluid, only 10.9% of the starting ester was hydrolyzed.