New thermo/pH -responsive materials containing ofloxacin. Preparation and physicochemical and invitro release behaviour.

CUGGINO, J.; CONTRERAS, C.; JIMENEZ KAIRUZ, AF.; ALBAREZ-IGARZABAL, C.

Córdoba

Congreso; 1ra. Reunión de Ciencias Farmacéuticas, RICiFa 2010; 2010

Facultad de Ciencias Químicas, Universidad Nacional de Córdoba.

Introduction A hydrogel is a kind of polymeric three-dimensional network that exhibits ability to absorb and to swell in water, maintaining its form until attaining a certain equilibrium balance. This ability makes them interesting materials as drug controlled release systems (1-4). In this work, the development of new hydrogels based in N-isopropylacrylamide/acrylic acid copolymer with potential utility as drug delivery systems by via oral was performed. Ofloxacin (Ofx), a fluoroquinolone antimicrobial agent, was selected as model drug. Materials and methods All hydrogels were prepared by free-radical crosslinking polymerization using N-isopropylacrylamide (NIPA) and acrylic acid (AAc) as monomers and diallyltartradiamide (DAT) as crosslinking agent. NIPA(100) and NIPA(70)/AAc(30) were yielded and analyzed by IR, equilibrium weight swelling ratio (qw), swelling kinetic, determination of rate of diffusion of water within the matrix, structural parameters of the network [molecular weight between crosslinking points (Mc), volume fraction of polymer in swollen state (v2s) and pore size (ξ)] and DSC and rheological studies. Release studies of materials as matrices were performed using USP-dissolution apparatus 2, at 50 rpm with 900 mL of simulated gastric (SGF, pH= 1.2) or intestinal (SIF, pH=6.8) fluids at 37 °C. Ofloxacin dissolved was measured by UV-spectroscopy at 287 nm. Kinetics data was calculated from release profiles. Results The products [NIPA(100) and NIPA(70)/AAc(30)] were obtained in rod shape with high yields. They presented different qw values (Table 1) and kinetic of swelling according the monomers composition and pH (6.8 and 1.2) or temperature (25 and 37°C) of the swelling medium. In general, NIPA(100) presented very high swelling ratios at both pH values at 25°C, while a drastic collapse was observed when the temperature increased at 37°C. At 25°C, the load of the matrix with Ofx produced a diminution of the swelling (at both pH values) due at a possible interaction drug-matrix, although a major rate of swelling was observed respect to the uncharged gels. The product NIPA(70)/AAc(30) presented high swelling behavior at 25°C at pH 6.8 while a diminution in swelling was observed at pH 1.2. A less pronounced collapse was observed, respect to NIPA(100), when the temperature increased at 37°C. Additionally, the drug loading in this material (31.2 % p/p) results 12.5 times higher than NIPA(100). A low release rate of Ofx (0,4 mg/min) and zero order kinetic was observed in SGF. Whereas, an increase close to 7.4 times in the release rate was observed with the pH change of dissolution medium. Additionally, a change in kinetic control (anomalous kinetic) was observed. These results could be associated with the physicochemical properties of hydrogels. Conclusions ?New hydrogels were prepared from NIPA, AAc and DAT. The effect of the incorporation of AAc into polyNIPA structures was analyzed. It was concluded that: ?The composition of monomers in the products and the temperature and pH of swelling influenced the network parameters of the hydrogels. ?High drug loading was reached ?The release rate of Ofx and the kinetic control was sensible to change of pH dissolution medium. The new material showed good properties to develop oral drug delivery systems with application on site-time controlled drug release.