Bile acids as functional excipients
Roger Viney, chief commercial officer, and Madalina Cociorb, business development specialist at ICE, show how bile acids can enhance drugs bioavailability in modern formulations
Pharmaceutical innovation increasingly relies on excipients that not only serve inert roles but also actively enhance drug delivery and performance. Among these, bile acids( BAs) have emerged as versatile agents capable of addressing long-standing formulation challenges, particularly in the solubilisation and absorption of poorly water-soluble drugs, the stabilisation of peptides and proteins, and improving the absorption throughout physiological barriers, thus increasing overall bioavailability.
Traditional excipients, like cellulose derivatives, surfactants and lipids, have been widely used to enhance drug solubility. However, their effectiveness can be limited, especially when dealing with biologics or drugs with poor aqueous solubility. These limitations necessitate the exploration of more bioactive and multifunctional compounds for drug delivery.
Having evolved for efficient lipid digestion and absorption, BAs present a naturally optimised scaffold for such purposes. Their dual hydrophilic and lipophilic character enables them to interact dynamically with both drug molecules and biological membranes.
Figure 1- Common bile acid chemical structure of bile acids3
Biosynthesis, structure & properties
BAs are synthesised in the liver from cholesterol through complex enzymatic steps, producing primary BAs such as cholic acid( CA) and chenodeoxycholic acid( CDCA). These are conjugated with glycine or taurine to form glyco- and tauro-conjugated bile acids, such as gycocholic acid( GCA), taurocholic acid( TCA), glycochenodeoxycholic acid( GCDCA) and taurochenodeoxycholic acid( TCDCA), and then stored in the gall bladder.
Upon fat ingestion, BAs are released into the duodenum where they form mixed micelles with lipids, aiding digestion and the absorption of fats and fat-soluble vitamins. In the ileum and colon, bacterial enzymes deconjugate and convert primary BAs into secondary BAs, mainly deoxycholic acid( DCA) and lithocholic acid( LCA), the latter being largely excreted due to its toxicity.
26 SPECIALITY CHEMICALS MAGAZINE ESTABLISHED 1981