Dissolution and Bioavailability of Phenytoin in Phenytoin-Polyvinylpyrrolidone-Sodium Deoxycholate Coprecipitate

The coprecipitates of Phenytoin (PHT) with combinations of carriers such as sodium deoxycholate and polyvinylpyrrolidone (DC-Na-PVP), sodium deoxycholate and polyethylene glycol (DC-Na-PEG), and sodium deoxycholate and hydroxypropylcellulose (DC-Na-HPC) were prepared. The dissolution characteristics of various coprecipitates were determined by the use of the JPX dissolution test apparatus in a pH 6.8 test medium. All of the coprecipitates prepared with combined carriers significantly enhanced the dissolution rate of PHT. Among them, the combination of PVP-DC-Na (1 : 1) as a carrier for the coprecipitate resulted in the fastest dissolution of PHT, but the dissolution rate of coprecipitate containing polyethylene glycol 4000 (PEG 4000), or hydroxypropylcellulose (HPC) was similar to that in the absence of the polymer. The dissolution rate of PHT coprecipitates with PEG 4000 and DC-Na, or HPC and DC-Na was silghtly enhanced in the medium containing 0.1% polysorbate 80. Unexpectedly, the PHT-DC-Na coprecipitate containing PVP showed a depressed dissolution rate in the same medium. A two-way cross-over study was carried out for a coprecipitate of PHT, DC-Na and PVP prepared in ratio of 1 : 1 : 1 (w/w) and the physical mixture of these ingredients in six rabbits. The area under the blood concentration-time curve of PHT following the administration of the coprecipitate was about 1.63 times that of the physical mixture in rabbits. It is suggested that PVP-DC-Na is a useful combination of carriers for PHT coprecipitates, considerably improving the dissolution and bioavailability of poorly water-soluble PHT.