The present study investigated the effect of co-grinding raloxifene HCL (RHCL) with different superdisintegrants, namely crospovidone (CP), croscarmellose sodium (CCS) and sodium starch glycolate (SSG), using a ball mill, in order to determine the potential effect on dissolution rate and bioavailability of raloxifene hydrochloride (RHCL). The dissolution studies of the co-ground compositions and the corresponding physical mixtures were carried out in U.S. Pharmacopeia (USP) Type II apparatus. The solid state interactions of the co-ground and the physical mixtures were evaluated by differential scanning calorimetry (DSC) and X-ray diffraction (XRD). The pharmacokinetics of co-ground mixture (1 : 5 RHCL : CP) and milled RHCL was evaluated following oral administration (25 mg/kg) in healthy female Sprague-Dawley rats. DSC studies showed that the crystalline nature of RHCL was reduced after co-grinding with superdisintegrants, while co-grinding with CP resulted in significant particle-size reduction of the mixture. Significant enhancement in dissolution rate was observed with co-ground mixture of RHCL with CP (1 : 5). The extent of the mean plasma exposures of RHCL was 7-fold higher in animals treated with co-ground mixture of RHCL, CP (1 : 5) compared to animals treated with milled RHCL. Co-grinding of RHCL with CP, reduced drug crystallinity, increased the rate and extent of dissolution, and improved bioavailability.
2010 The Pharmaceutical Society of Japan