In Vitro Bioequivalence Study of Bile Acid Sequestrates By HPLC

Abstract

Bile acids are important in the processing of dietary lipids and serve three major newlinefunctions. Bile acids aggregate and form micelles in the upper small intestine, which newlinehelp solubilize lipolytic products, cholesterol and fat soluble vitamins, thus facilitating absorption across the intestinal epithelium. Bile acids stimulate bile flow during their secretion across the biliary canaliculus. Finally, bile acids are major regulators of sterol metabolism and serve as a major excretory pathway for cholesterol from the body[1].Bile acids (BAs) are synthesized in the liver (only) from cholesterol (CH), and are newlineconjugated with the amino acids glycine and taurine, and in some animals, sulfate newline(SO4). Conjugation adds polar constituents to these fat-soluble compounds, thus newlinerendering them more water-soluble and less likely to precipitate in a watery medium newline(e.g., bile). The active transport of these osmotically active steroidal compounds newlineacross canalicular membranes of hepatocytes provides a primary driving force for bile newlineflow, and following their secretion into bile they are normally concentrated and stored newlinein the gallbladder (in animals possessing a gallbladder). When the gallbladder newlinecontracts following movement of lipid-rich chyme into the duodenum, BAs and other newlineconstituents of bile are delivered to the small bowel, where they function to emulsify newlinedietary lipid, promote its digestion and absorption, and also assist in the absorption of CH and the fat-soluble vitamins. Other important lipids secreted into bile are lecithin (phosphatidylcholine), free CH (i.e. biliary cholesterol (BC)) and bile pigments (e.g.,bilirubin-glucuronides, -glucosides, and -xylosides). Sodium and K+ salts of the BAs are referred to as bile salts (BSs), and form in the alkaline milieu of bile. Although the two terms, BAs and BSs, are generally used interchangeably, BSs are generally newlineconsidered to be better emulsifying agents than BAs[2].The drug molecules selected for the study belong to Bile acid sequestrants (BASs) or resins, they are non-abso