Enhanced Bioavailability of Probucol Following the Administration of Solid Dispersion Systems of Probucol–Polyvinylpyrrolidone in Rabbits

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Disks of probucol and solid dispersion systems of probucol–polyvinylpyrrolidone (PVP) in various weight ratios were prepared. Dissolution of probucol was markedly increased in the solid dispersion systems in J.P. XV disintegration media No. 1 (pH 1.2) and No. 2 (pH 6.8). The concentrations of probucol after the dissolution of the disks of solid dispersion systems showed supersaturation. Following the administration of disks of solid dispersion systems in rabbits, a marked increase in the area under the plasma concentration time curve (AUC) was observed. When the weight ratio of PVP to probucol was larger, a larger AUC was observed. When disks of the 1 : 9 solid dispersion system (weight ratio of probucol : PVP=1 : 9) containing 50 and 100 mg probucol were respectively administered, AUC values were approximately proportional to the dose. AUC values following the administration of disks of the 1 : 9 solid dispersion systems containing 15 mg probucol (total weight: 150 mg) and 500 mg probucol were approximately equal. The mean half life (t1/2) was 12 h when disks of the 1 : 9 solid dispersion system were administered, whereas the t1/2 was 35 h when probucol disks were administered. The markedly increased dissolution of probucol in solid dispersion systems resulted in a marked increase in its bioavailability.