Excipients are inactive ingredients added to drug formulations, influencing a medication’s stability, appearance, and drug delivery. Bile acids are naturally occurring compounds with unique properties, making them valuable as excipients.
Understanding Bile Acids as Excipients
Bile acids are naturally occurring steroid molecules synthesized in the liver from cholesterol in vertebrates, including humans. Examples include cholic acid and chenodeoxycholic acid, which are primary bile acids. They undergo modifications in the body, leading to secondary bile acids like deoxycholic acid and lithocholic acid. These molecules possess a rigid, saturated tetracyclic hydrocarbon ring structure, along with a short aliphatic side chain ending in a carboxyl group.
Their unique chemical structure makes bile acids amphiphilic, meaning they have both hydrophobic (water-repelling) and hydrophilic (water-attracting) regions. The steroid nucleus forms the hydrophobic convex side, while hydroxyl and carboxyl groups create the hydrophilic concave side. This dual nature allows them to interact with both fatty and watery environments, making them suitable for improving drug stability and aiding in the formation of dosage forms. For instance, they can help prevent the precipitation of drugs in aqueous solutions.
How Bile Acid Excipients Enhance Drug Delivery
Bile acid excipients are particularly useful in addressing challenges related to drug solubility and absorption. Many active pharmaceutical ingredients are poorly soluble in water, which can limit their effectiveness as they may not dissolve properly in the body to be absorbed. Bile acids overcome this by forming micelles, which are tiny spherical structures that can encapsulate hydrophobic drug molecules within their oily core. This allows the drug to effectively dissolve in the body’s aqueous environment, improving its solubility and subsequent absorption.
Beyond micelle formation, bile acids also contribute to drug delivery through their emulsifying properties. They can break down fats and oils into smaller droplets, forming stable emulsions. This is particularly relevant for lipid-based drug formulations, where they help ensure the uniform dispersion of the drug. Bile acids can also enhance drug absorption by transiently influencing cell membranes. They can modulate the fluidity of biological membranes and, in some cases, widen tight junctions between cells, thereby promoting the passage of drug molecules across these barriers.
Key Applications and Examples in Medicine
Bile acid excipients are applied in a range of pharmaceutical products, especially those containing drugs with low aqueous solubility or poor absorption. They are frequently used to enhance the delivery of fat-soluble vitamins, certain antibiotics, and immunosuppressants. Common bile acid excipients include sodium cholate, sodium deoxycholate, and sodium taurocholate (a taurine conjugate of cholic acid), all of which enhance solubility and absorption.
These excipients are considered safe for pharmaceutical use and are incorporated into both conventional oral dosage forms and advanced drug delivery systems, such as polymeric micellar systems. Their ability to improve the bioavailability of poorly soluble drugs has led to their inclusion in various oral and injectable medications. Research continues to explore their potential in other delivery methods, including transdermal and nasal applications, highlighting their versatility and ongoing relevance in pharmaceutical formulation.