Optimization of thermosensitive chitosan hydrogels for the sustained delivery of venlafaxine hydrochloride.

Chitosan/glycerophosphate disodium (GP) thermosensitive hydrogels were prepared for the sustained delivery of venlafaxine hydrochloride (VH) and optimization of this formulation was mainly studied. Release mechanism was investigated by applying various mathematical models to the in vitro release profiles. Overall, drug release from the hydrogels showed best fit in first-order model and drug release mechanism was diffusion-controlled release. Optimization of VH chitosan/GP thermosensitive hydrogels was conducted by using a three-level three-factorial Box-Behnken experimental design to evaluate the effects of considered variables, the strength of the formulation, chitosan concentration and GP amount, on the selected responses: cumulative percentage drug release in 1h, 24h and the rate constant. It presented that higher strength and GP concentration resulted in higher initial release and rate constant, which supported the hypothesis that the kinetic gelation mechanism of this system was nucleation and growth. Drug release profiles illustrated that controlled drug delivery could be obtained over 24h, which confirmed the validity of optimization. In vivo pharmacokinetic study was investigated and it demonstrated that compared with VH solution, chitosan/GP thermosensitive hydrogels had a better sustained delivery of VH.