PHARMACEUTICALS
can also support the formulations and aid the delivery of biologics and vaccines, improving the stability and controlled release of monoclonal antibodies, enzymes and RNA-based drugs.
Oral delivery is the most convenient route for drug administration and the most acceptable for the patient. Formulations incorporating BAs make it possible to enhance solubilisation, and stabilise and enhance the permeability of a range of poorly soluble drugs and macromolecules.
Compared to traditional permeation enhancers, BAs offer a more versatile and physiologically compatible alternative, with additional benefits in terms of safety, efficacy and multifunctionality. As such, BAs stand out as excipients for advancing oral drug delivery.
When the formulation reaches the enterocytes, the absorbed drug may enter either the lymphatic or the portal vein-to-liver pathway. Lymphatic delivery is attracting extensive research interests as the drugs transported via this pathway directly enter systemic circulation without going through first-pass effects by the liver, which usually reduces bioavailability by exposing the drug to potential metabolic deactivation or activation.
Due to their permeation-enhancing properties, BAs can be used to facilitate the transport of drugs across the stratum corneum( transdermal), nasal epithelium( intranasal) and sublingual / buccal. These routes of administration make it possible to bypass first-pass metabolism and can be targeted when the parenteral and oral administration are not the most suitable.
Regulatory & safety considerations
The endogenous origin of BAs— being naturally synthesised from cholesterol in the human liver and
CATEGORY BILE ACIDS ABBREVIATION Primary bile acids Cholic acid CA
Chenodeoxycholic acid
CDCA Secondary bile acids Deoxycholic acid DCA
Lithocholic acid Conjugated bile acids Taurocholic acid TCA
Table 1- Categorisation of bile acids
Glycocholic acid Taurochenodeoxycholic acid Glycochenodeoxycholic acid
secreted into the gastrointestinal tract— confers high physiological compatibility and low immunogenicity. Unlike synthetic surfactants, BAs are biodegradable, efficiently reabsorbed through the enterohepatic circulation and excreted from the body, limiting systemic accumulation.
The inclusion of BAs in pharmaceutical products requires careful consideration of concentration-dependent effects. In fact, high levels can lead to detergentlike properties and membranolytic effects. This effect is common to all surfactant excipients that are used in pharmaceutical dosage forms, so the implications for safety in humans depend on the formulation type, exposure levels over time and the route of administration.
Regulatory agencies have recognised specific BAs as safe under certain usage parameters, with CA, DCA, GCA and TCA all having GRAS( Generally Recognised As Safe) status. On top of the current commercialised products having shown the safety on the use of this category of excipients, BA-based derivatives have been investigated in various investigational drug formulations— particularly in oral delivery systems for peptides, proteins and poorly water-soluble drugs— demonstrating favourable safety profiles in both preclinical and early-phase clinical trials.
Formulators must balance efficacy and safety, often optimising
References: 1: N. Pavlović, S. Goločorbin-Kon, M. Ðanić, B. Stanimirov, H. Al-Salami, K. Stankov & M. Mikov, Front. Pharmacol., November 2018, 9, 1283. 2: K. Baker, R. Sikkema & I. Zhitomirsky, Med. Devices Sens., 2020, 3, e10119. 3: K. Lei, M. Yuan, T. Zhou, Q. Ye, B. Zeng, Q. Zhou, A. Wei & L. Guo, Steroids, 2021, 173, 108879. 4: S. Maher, C. Geoghegan & D. J. Brayden, Adv. Drug Deliv. Rev., 2023, 202, 115086.
LCA
GCA TCDCA GCDCA
concentrations through in vitro and in vivo studies to define the therapeutic window and ensure patient tolerance. It is also important to evaluate excipient-drug interactions, stability under storage conditions and compatibility with packaging materials.
Future directions & opportunities
With the rise of biologics, mRNA therapeutics, and personalised medicine, there is growing interest in BAs as delivery enhancers for complex molecules. Their integration in novel formulations offers promising platforms for targeted and responsive delivery.
In vaccine delivery, BAs may serve as both adjuvants and stabilisers. Studies suggest that BA-based carriers can enhance antigen uptake and promote mucosal immunity. This is particularly relevant for needle-free vaccine strategies via oral or other relevant routes.
Emerging research is also focused on semi-synthetic BA derivatives, which retain the amphiphilic nature of natural BAs but are optimised for specific pharmacokinetic profiles and reduced cytotoxicity. ● Madalina Cociorb
ICE SPA
+ 39 345 563 6193 k m. cociorb @ icepharma. com J sales @ icepharma. com j www. icepharma. com /
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