Venlafaxine-loaded sustained-release poly(hydroxyethyl methacrylate-co-itaconic acid) hydrogel composites: their synthesis and in vitro/in vivo attributes

Abstract

Hydrogels have potential applications as sustained-release drug delivery systems, as an example in treatment of major depressive disorders. This paper reports some works carried out to obtain a new type of copolymeric hydrogel for an anti-depressant drug. The copolymerization of itaconic acid, hydroxyethyl methacrylate (HEMA), and tetraethyleneglycol dimethacrylate was performed. The gels were evaluated for swelling, diffusion coefficient, drug incorporation, in vitro dissolution, and in vivo performance in rabbits after oral administration. The pharmacokinetic parameters like bioavailability, Cmax and Tmax were calculated for hydrogels in comparison to oral solution containing equivalent amount of venlafaxine. The HEMA-based matrices showed negligible swelling and release rate of venlafaxine, which were also very low in a buffer of pH 1.2. However, both the swelling and release rate of venlafaxine were faster at high pH (6.5 and 7.5). The Tmax of the formulation with the highest swelling and release rate (T1) were found at 600 min compared to that at 180 min for oral solution having equivalent quantity of venlafaxine. AUC0–∞ for oral hydrogel was 2.1 times greater than that for oral solution of venlafaxine. Similarly, MRT for hydrogel was 3.1 times more than that for oral solution. However, Cmax for oral cross-linked hydrogel composite was significantly lower than that for equivalent amount of oral drug solution. The synthesized hydrogel composites showed a promising ability for sustained release of venlafaxine both in vitro and in vivo. It was found that venlafaxine delivery through oral route was practical.