Preparation and release of model drugs from thermally sensitive poly(N-isopropylacrylamide) based macrospheres

Abstract

Emulsion polymerization was employed to prepare poly(N-isopropylacrylamide) hydrogel spheres, which exhibited an LCST of 32°C. The hydrogels were loaded with model drugs (benzoic acid (BA), sodium benzoate and diltiazem HCl (DHCl)) and release investigated at 25°C and 37°C. The temperature at which gel formation occurred was vital for successful hydrogel preparation, macrosphere formation not occurring when the temperature was close to the LCST. Sphere size increased on decreasing the stirring rate and on slowing the rate of addition of the aqueous phase. Pulsatile delivery was investigated using BA and DHCl. For both compounds a pulse was observed with a change in temperature. Pulsed release of the smaller model drug of lowest solubility, BA, was more successful. Drug release from hydrogel spheres was, therefore, found to be dependent on the physicochemical properties of the drugs, with pulsatile release of low molecular weight compounds, by temperature cycling, difficult to control.