Characterization of Multi-Sourced Diclofenac Sodium Extended-Release Tablet Dissolution Profiles: A New Approach to Establish an In vitro-In vivo Correlation Based on Multiple Integral Response Surface

• Published in: Journal of pharmaceutical innovation Vol. 10; no. 4; pp. 302 - 312
• Main Authors: Ning, Baoming, Liu, Xi, Luan, Hansen, Tu, Jiasheng, Li, Huiyi, Chen, Guiliang, Wang, Hao, Sun, Chunmeng
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.12.2015
• Subjects: Biochemical Engineering; Biomedical and Life Sciences; Biomedicine; Biotechnology; Industrial and Production Engineering; Pharmacology/Toxicology; Research Article; Diclofenac sodium; Pharmacokinetics; In vitro-in vivo correlations (IVIVCs); Volume under response surface (VUR)
• ISSN: 1872-5120; 1939-8042
• DOI: 10.1007/s12247-015-9227-4

Purpose In this study, a new parameter, volume under response surface (VURS), based on the multiple integrals response surface (MIRS) was applied to establish in vitro-in vivo correlations (IVIVC) refer to in vitro dissolution data and in vivo pharmacokinetic data. Materials and methods The in vivo predictive capacity of f 2 factor, dissolution efficiency (DE), and VURS were compared by investigating the multi-sourced diclofenac sodium extended-release tablets. In vitro dissolution tests were investigated under various conditions. Beagle dogs were used for in vivo pharmacokinetic study as a preliminary investigation of the new approach. In vivo pharmacokinetic experiments were conducted based on the crossed-over design principle, and the blood concentration was determined by LC-MS/MS method. Results Data indicated both DE value and f 2 factor were unable to discriminate the significant difference in relative bioavailability among the test formulations, although they could suggest in vivo bio-inequivalent risk to some extent. VURS is successfully explored to establish an IVIVC in beagle dogs with diclofenac sodium extended-release formulations with similar release mechanism. Conclusions Compared with DE value and f 2 factor, the advantage of VURS was demonstrated to predict in vivo parameters of test formulation with a similar or dissimilar release mechanism.