Novel controlled release hydrogels formulation based on dendritic anionic polyelectrolyte-ciprofloxacin complexes

GARCÍA, MC.; CUGGINO, J.; MANZO, RH.; ALVAREZ IGARZABAL, C.; JIMENEZ KAIRUZ, AF.

Rósario

Congreso; 2ra. Reunión Internacional de Ciencias Farmacéuticoas RICiFa 2012.; 2012

Universidad Nacional de Rosario

Introduction Hydrogels are three-dimensional, cross-linked networks of water soluble polymers. A particular class of hydrogels are that based on drug-polyelectrolite (D-PE) complexes, where a molecular dispersion of D is ionically bounded at the ionizable groups of polyelectrolyte network (1-4). The unique physical properties have sparked particular interest in their use in drug delivery applications formulated in a variety of physical forms (5). Recently, a new anionic dendritic polylelectrolyte (DP) was synthesized by aqueous free-radical polymerization of a particularly prepared vinyl monomer derivate from Behera´s amine (6). In previous work, DP was considered as a potential non toxic material, according to ISO 10993-5 and its complexes with free base Ciprofloxacin (Cip) showed acceptable microbiological activity, 38 - 58% versus S.aureus y P.aeruginosa respectively, when was compared with Cip solution (7). This interdisciplinary work focuses on the integral evaluation of DP as antimicrobial carrier with potential use in the design of drug delivery systems for topical and mucosal administration. Ciprofloxacin was selected as ionizable model drug because of its wide use in common topical opportunist infections. Materials and Methods. DP-Cip complexes were prepared by solvent evaporation, by mixing in a mortar powered dried disc of DP (cross-linked 0.5, 2 and 4 % of (+)-N,N’-diallyltartramide) with an appropriate amount of free base Cip and ethanol for 10 min. The blend was kept at room temperature for 24 h and then dried until constant weight at 40 °C. FTIR spectroscopy, powder XR diffraction, thermal analysis, optical microscopy and oscillatory rheology were performed to evaluate DP and Cip interactions. By redispersing of powdered DP-Cip on distilled water, adding an appropriate amount of 1M NaOH solution in order to obtain hydrogels. In vitro release studies in diffusion Franz cells, using water, 0.9% NaCl, pH 6.8 USP-buffer solution as receptor media, were performed. Results FTIR, PXRD, DSC and optical microscopy analysis showed a partial ionic interaction between DP, with different cross-linked grades, and Cip. Opaque and stable hydrogels of complexes with pH in the range of 6.2 to 6.8 were obtained. Viscoelastic measurement showed a predominant storage moduli that increase with drug loading and cross-linking grade. Hydrogels exhibited slow release of Cip towards water. As water was replaced by NaCl solution release rate raised significantly (3 to 5 times). A intermediate behavior was observed using buffer solution. Release profiles was fitted to Peppas equation and not significant differences with cross-linking grades (p  0.05). Discussion and conclusions New controlled release hydrogels formulation based on dendritic anionic polyelectrolyte-ciprofloxacin complexes were developed. The systems were physically stables, highly biocompatible and behave as reservoir of Cip. In addition, showed acceptable microbiological activity with promising mechanical behaviors for topical and mucosal administration.