Comparative Pharmacokinetic and Relative Bioavailability Study of Ursodeoxycholic Acid Tablets in Healthy Indian Volunteers

The best bile acid therapy currently available is ursodeoxycholic acid (UDCA), which is a bile salt that both reduces the secretion of cholesterol into bile and increases cholesterol solubility. The aim of this study is to compare pharmacokinetic parameters as well as relative bioavailability of the developed enteric coated tablet of UDCA 300 mg prepared from micronized drug (MCUDCA) with respect to film coated tablet of UDCA 300 mg prepared from nonmicronized drug (NMUDCA) available in the market on healthy human volunteers. A simple and sensitive LC-MS/MS was developed to detect and quantify UDCA with a LLOQ of 50ng/ml and using Valsartan as internal standard in human plasma. The method was validated as per the guidelines of US FDA bioanalytical method validation. The linearity of the method (concentration ranging from 50-10000 ng/ml), extraction recovery and accuracy were 0.9988, 82.39 91.34 % and 99.60-103.63 % respectively. Comparative pharmacokinetic study revealed that tmax was same for the two types of the formulations and it came around three and half hour. The in vivo pharmacokinetic performances of micronized formulation were much better than non-micronized one. The mean Cmax of UDCA from MCUDCA 300 mg enteric coated tablet was 5091.806ng/ml whereas Cmax of the drug in the NMUDCA formulation was 4848.66ng/ml. So it can be said that this improvement of plasma drug concentration was due to particle size reduction or micronization. The relative bioavailability study revealed that the enteric coated tablets prepared with micronized UDCA were 112% when compared with marketed UDCA tablets prepared with nonmicronized drug. So, it can be concluded that enteric coated tablets 300 mg prepared with micronized UDCA had generated better promising result when compared with the non-micronized type with respect to the pharmacokinetic parameters.