Extended-Release Divalproex Sodium Tablets: Formulation Strategies and In-Vitro Evaluation

Background: Divalproex Sodium, an antiepileptic drug, is widely used for epilepsy, migraine prophylaxis, and bipolar disorder.However, its clinical utility is limited by a narrow therapeutic index, dose-dependent hepatotoxicity, short half-life, and poor bioavailability.Developing an extended-release (ER) formulation can enhance therapeutic efficacy by ensuring sustained drug release and improving patient compliance.Objective: This study aims to formulate, optimize, and evaluate ER tablets of Divalproex Sodium to overcome the limitations of conventional dosage forms while achieving controlled drug release.Methods: Matrix-based ER tablets were prepared using hydrophilic and hydrophobic polymers, with Hydroxypropyl Methylcellulose (HPMC) as the primary release-modifying agent.Pre-formulation studies confirmed excellent flow properties and good compressibility.Response Surface Methodology (RSM) optimized the drug-to-polymer ratio.Formulations were assessed for weight variation, hardness (13-14 kg/cm), friability (<1%), drug content (97.43%-99.61%),dissolution, and stability at 40C/75% RH for one month.The dissolution behavior of the optimized formulation (F8) was compared with Depakote ER. Results:The optimized formulation (F8) exhibited a dissolution profile (99.84%) bioequivalent to the reference product (98%).Drug release followed Higuchi's model (R = 0.974-0.994),with Korsmeyer-Peppas slope values (0.414-0.443) indicating Fickian release.ANOVA results (F = 17.16, p < 0.005) confirmed model significance (89.72% variability).Stability studies showed no significant changes in parameters. Conclusion:The optimized ER formulation provides sustained drug release, improved efficacy, and better patient compliance, demonstrating the potential of extended-release technology in overcoming conventional formulation challenges.