In vivo Evaluation of Fluvoxamine Maleate Mouth Dissolving Films by Design of Experiment

Abstract

Fluvoxamine, an antidepressant belonging to serotonin reuptake inhibitor (SRI) class, exhibits maximum absorption through the oral route of administration. The objective of current research is to formulate mouth dissolving fluvoxamine films by employing super disintegrants. The central composite design (CCD), employed to examine the effects of amount of hydroxypropyl methylcellulose (HPMC) E15 (A), amount of eudragit RL 100 (B), amount of polyethylene glycol (PEG 4000) (C) on response variables tensile strength, disintegration time and cumulative % drug released. A 27 formulations prepared according to CCD and evaluated for physicochemical parameters and in vitro dissolution studies. Fluvoxamine mouth dissolving films formulated by employing solvent-casting method using HPMC E15, eudragit RL100, and PEG 4000. CCD is employed to optimize the effective dosage of formulation superdisintegrants. FF15 with a maximum tensile strength of 55.63 ± 1.37 mg, least disintegration time of 10 ± 1.85 seconds, and highest drug release of 98.29 ± 1.87 % is chosen as an optimal formulation with maximum content uniformity and folding endurance. From in vivo bioavailability studies, Cmax and Tmax of the fluvoxamine optimized mouth dissolving film formulation were significant (p is less than 0.05) compared to the fluvoxamine marketed product formulation. AUC0-∞ infinity for the optimized formulation was higher (733.84 ± 2.04 ng.h/mL) than the fluvoxamine marketed product formulation (485.67 ± 1.54 ng.h/mL). Statistically, AUC0-t of the optimized mouth dissolving film formulation was significantly higher (pis less than 0.05) than fluvoxamine marketed product formulation. In vivo pharmacokinetic studies in rabbits confirmed the quick release and increase in bioavailability for fluvoxamine from optimized mouth dissolving film formulation as compared to the fluvoxamine marketed product formulation.