ENHANCEMENT OF DISSOLUTION RATE OF PROBENECID IN PHOSPHOLIPID COPRECIPITATES

The coprecipitates of probenecid (PBC) with various phospholipids (PL) were prepared and their dissolution characteristics were determined by use of a Vanderkamp dissolution test apparatus. Probenecid exhibited significantly improved dissolution rates in all the PL preparations compared to either the physical mixtures or the pure PBC. Among them, the combination of PBC:Egg phosphatidylcholine (EPC) (10:1) as a carrier for the coprecipitate resulted in the fastest dissolution of PBC. A 13.7 fold greater initial dissolution rate and 7.5 fold greater limiting concentration was achieved. Dissolution studies of probenecid suggested that less than 1 to 10 ratio of PBC to PL was required to disperse amorphous PBC completely in the carrier. Increasing the lecithin content further did not improve the release of the drug to any significant extent. Phospholipids with phase transition temperature higher than the experimental temperature exhibited significantly less increase in dissolution compared to other phospholipids. Various coprecipitating solvents used in the study were found equally good in improving the dissolution of the drug. The PBC-PL solid dispersion, therefore, appears to have the clinical advantages of quick release and excellent bioavailability.