Enhanced dissolution and bioavailability of raloxifene hydrochloride by co-grinding with different superdisintegrants.
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.
Jagadish
Balasubramaniam
B
International Specialty Products India (Pvt) Limited, Hyderabad-500 082, India.
Yelchuri
Rajesh
R
K
Bindu
B
Tangi
Hemalatha
H
Maroju
Swetha
S
Rao
Vinay Umesh
VU
D000818:Animals; D001682:Biological Availability; D002152:Calorimetry, Differential Scanning; D002266:Carboxymethylcellulose Sodium / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D005260:Female; D010316:Particle Size; D011205:Povidone / Q000737:chemistry*; D020849:Raloxifene Hydrochloride / Q000737:chemistry* / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D013213:Starch / Q000031:analogs & derivatives* / Q000737:chemistry; D013499:Surface Properties; D013696:Temperature; D014018:Tissue Distribution; D014961:X-Ray Diffraction
D020849:Raloxifene Hydrochloride; D013213:Starch; C048390:sodium starch glycolate; D011205:Povidone; D002266:Carboxymethylcellulose Sodium