Characterization and in vitro evaluation of an (ipn)-hydrogel for transdermal delivery of diltiazem.

Aim The aim of this work was the preparation and the evaluation of an interpenetrating polymer network (IPN)-hydrogel composed of a polyvinyl alcohol (PVA)/chitosan (CS) mixture for transdermal drug delivery. Materials and Methods The IPN-hydrogel was prepared by dissolving the CS in 10% (w/w) solution of PVA acidified with lactic acid, and adding Glyoxal at 50°C as crosslinking agent and was characterized by Fourier-transform infrared spectroscopy (FTIR) and by Differential Scanning Calorimetry (DSC). The dynamic swelling behavior of the PVA/chitosan IPN-hydrogel was studied at 32°C by immersion of the hydrogel both in pH 5.2 phosphate buffer solution (PBS) and in deionised water. It was used to prepare matrices containing diltiazem hydrochloride as a model drug, alone (M1) or added of penetration enhancers: PEG-8 caprylic/capric glycerides (Labrasol®, M2) and C1-C9-Br-morpholinium (a room temperature ionic liquid, M3). Each matrix was submitted to in vitro release test using the paddle-over-disk method (Apparatus 5, USP 29) and 500 ml of PBS pH 5.2 as dissolution medium; the drug concentration in dissolution medium, withdrawn at predetermined time intervals, was quantified by HPLC method. Moreover, in vitro permeation through hairless rat skin of drug from the formulations was determined using Gummer-type vertical cells. Results and Discussion The FTIR spectra of crosslinked IPN-hydrogel showed a reduction of the peak intensity at 1580 cm-1 with respect to uncrosslinked hydrogel, probably due to the reduction of free-NH2 groups of chitosan. DCS analysis highlighted an increase of tg value when compared to uncrosslinked matrix. The formation of a crosslinked polymeric structure leads to a considerable reduction in mobility and to an increase rigidity of the polymer. The swelling index (SI) of the IPN-hydrogel was higher in deionised water, arising up to 1400 % of the initial weight, while the SI was 30 % in PBS solution. The drug release from M1, M2 and M3 formulations was characterized by a diffusive mechanisms and the amount of drug permeated through the skin was related to the physico – chemical characteristics of the matrices. The preliminary results confirm that INP-hydrogel could be useful to diffusion-controlled system for hydrophilic drug solubilised in the matrix