Enhancement of ursodeoxycholic acid bioavailability by cross-linked sodiumcarboxymethyl cellulose

The bioavailability of ursodeoxycholic acid from a new formulation based on drug-loaded cross-linked sodium carboxymethyl cellulose was studied in man . The plasma levels of ursodeoxycholic acid were determined by gas chromato graphy-mass spectrometry after derivatization and sample purification by so lid-phase extraction. Capsules containing the drug/polymer system were prep ared and compared with conventional commercial ursodeoxycholic acid capsule s after single oral administration using a randomized crossover experimenta l design. Although the drug/polymer system improved the in-vitro dissolution rate of ursodeoxycholic acid in simulated intestinal fluid, statistical evaluation of the area under the plasma concentration curves indicated no significant difference in the extent of bioavailability between the two formulations (1 4.93+/-4.43 vs 14.95+/-5.79 mu M h; P > 0.2). However, following the admini stration of the ursodeoxycholic acid/cross-linked sodium carboxymethyl cell ulose system with an enteric-coated capsule, the mean area under the plasma concentration curve (27.60+/-10.11 mu M h) was significantly higher than t hat obtained after treatment with the commercially available ursodeoxycholi c acid capsule (16.24+/-8.38 mu M h; P < 0.05). We concluded that improved intestinal absorption of the drug was obtained w ith enteric-coated capsules filled with the ursodeoxycholic acid/polymer sy stem. Moreover, the simplicity of the preparation and the non-toxicity of t he polymer used as the carrier represented additional advantages of this do sage form.