In vitro and in vivo comparison of two diclofenac sodium sustained release oral formulations

• Published in: International journal of pharmaceutics 2003-07, Vol.260 (1), p.39-46
• Main Authors: Su, Sheng-Fang, Chou, Chen-Hsi, Kung, Chao-Feng, Huang, Jin-ding
• Format: Article
• Language: English
• Subjects: Administration, Oral; Adult; Anti-Inflammatory Agents, Non-Steroidal - administration & dosage; Anti-Inflammatory Agents, Non-Steroidal - blood; Anti-Inflammatory Agents, Non-Steroidal - pharmacokinetics; Area Under Curve; Biological and medical sciences; Bones, joints and connective tissue. Antiinflammatory agents; Chromatography, High Pressure Liquid; Cross-Over Studies; Delayed-Action Preparations; Diclofenac; Diclofenac - administration & dosage; Diclofenac - blood; Diclofenac - pharmacokinetics; Dissolution; Humans; Hydrogen-Ion Concentration; Male; Medical sciences; Pharmacokinetic; Pharmacology. Drug treatments; Solubility; Sustained release
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/S0378-5173(03)00237-0

The aim of this study was to investigate the effect of formulation on the pharmacokinetics of diclofenac in two sustained release formulations (formulation A and Voltaren SR ®) after oral delivery. The dissolution of diclofenac from sustained release formulation was pH-dependent. While drug released from both formulations increased with increased pH, the release kinetics of these two formulations was different. The pharmacokinetic study was conducted in 12 healthy subjects administered with multiple doses of 100 mg of diclofenac in a crossover design. There was a significant difference in area under the plasma concentration–time curve [AUC(0–24)] and C max observed. The formulation with a reduced diffusion exponent with increased kinetic constant results in increased absorption of diclofenac in vivo. This study demonstrated the impact of release mechanism of the formulation on the absorption in vivo.