Effects of bile salts on gastrointestinal absorption of pravastatin.

摘要

This study aimed to examine the effects of bile salts and formulations on the absorption through gastrointestinal tract of pravastatin, which has low bioavailability. Pravastatin sodium physical mixtures and solid dispersions were prepared using various bile salts. The physicochemical characteristics and permeation profiles were investigated using pravastatin sodium-bile salt physical mixtures and solid dispersions. Pravastatin in the physical mixture did not achieve amorphous state, whereas that in the solid dispersion was completely converted to amorphous state. The permeation enhancement factors ranged between 1.13 and 11.9 with the addition of bile salts, and the permeation flux of pravastatin sodium greatly increased as the sodium cholate (NaC) concentration increased from 5 to 10 mM. Pravastatin sodium permeation fluxes [μg/(cm(2) h)] from solid dispersions (drug-NaC = 1:49) (20.8 ± 2.7) were much higher than those from physical mixtures (4.7 ± 3.1) and commercial tablets (3.5 ± 1.2) (p < 0.05). The dissolution rates of pravastatin sodium from solid dispersions in pH 1.2 were much lower than those from physical mixtures and commercial products, whereas more than 97% of pravastatin sodium was dissolved at 5 min in pH 6.8. On the basis of the results, it was concluded that pravastatin sodium solid dispersions containing bile salts could enhance drug absorption.