Wet Granulation as Innovative and Fast Method to Prepare Controlled Release Granules Based on an Ion-Exchange Resin

The goal of this work was to evaluate the suitability of wet granulation as an innovative and fast method for the preparation of granules containing a drug-resin complex (resinate), having cholestyramine as resin and potassium diclofenac (KD) as drug. Resinate and granules were prepared directly by steam granulation in high shear mixer (method A), using two different amount of resin (granules 1 and 2). For comparison granules 1 were also prepared by conventional batch method followed by steam granulation (method B). All granules showed quite irregular shape, main size fractions between 75 and 500 microm, good flowability and uniform KD distribution. Granules 1A exhibited controlled release profiles at pH 7.4, while granules 2A showed a burst effect due to KD free crystals. FT-IR studies confirmed the complete complexation between resin and KD during the granulation process with method A for granules 1. Finally, the dissolution test of granules 1A in different media revealed a controlled drug release in 12 h, providing the utility of this system for enteric drug delivery. Granules 1B evidenced similar characteristics to those of granules 1A; the drawback of the multistep procedure was related to the long processing time. (Copyright) 2008 Wiley-Liss, Inc