Enhanced bioavailability of probucol following the administration of solid dispersion systems of probucol-polyvinylpyrrolidone in rabbits.
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 (t(1/2)) was 12 h when disks of the 1 : 9 solid dispersion system were administered, whereas the t(1/2) 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.
Kubo
Yoshitada
Y
Department of Pharmaceutics, School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, 1757Kanazawa, Ishikari-Tohbetsu, Hokkaido 061-0923, Japan. y-kubo@hoku-iryo-u.ac.jp
Terashima
Yuuji
Y
Yagi
Naomi
N
Nochi
Hiromi
H
Tamoto
Koichi
K
Sekikawa
Hitoshi
H
D000284:Administration, Oral; D000818:Animals; D000924:Anticholesteremic Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D008297:Male; D011205:Povidone / Q000008:administration & dosage*; D011341:Probucol / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D011817:Rabbits; D012995:Solubility
D000924:Anticholesteremic Agents; D011205:Povidone; D011341:Probucol