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

Abstract

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.Keyword Diclofenac sodium . Pharmacokinetics . Volume under response surface (VUR) . In vitro-in vivo correlations (IVIVCs)

Development of an Extended-Release Formulation for Apremilast and a Level A <i>in Vitro</i>–<i>in Vivo</i> Correlation Study in Beagle Dogs

“…It serves for several purposes such as optimizing formulations, confirming the quality control parameters of in vitro release experiment and allowing minor changes of dosages after launching the market without providing new bioequivalence data. 24,31,32) At the early stage of modified release product development, an IVIVC study on animals can provide substantial information on the suitability of the formulations and the settings of dissolution experiment. As the in vivo data was analyzed as Table 5).…”

Effect of Specific Surface Area and Hydrophobicity of Electrospun Nanofibers on the Sustained Release Performance of Diclofenac Sodium

“…The analgesic effect is more potent than that of indomethacin and aspirin . DS may irritate the stomach, leading to gastrointestinal problems and gastric ulcers. , DS has a brief half-life ranging from 1.1 to 1.8 h, requiring administration three times daily, leading to fluctuations in blood levels known as “peaks and valleys.” Developing an effective slow-release medication for DS could minimize gastrointestinal irritation and enhance treatment stability. Roberts et al utilized hydroxypropyl methylcellulose to merge wet granulation with liquid adhesive dosage forms in order to attain sustained-release of DS .…”

“…4 DS may irritate the stomach, leading to gastrointestinal problems and gastric ulcers. 5,6 DS has a brief half-life ranging from 1.1 to 1.8 h, requiring administration three times daily, leading to fluctuations in blood levels known as "peaks and valleys." 7 Developing an effective slow-release medication for DS could minimize gastrointestinal irritation and enhance treatment stability.…”