Improved drug formulation to boost delivery of oral medication to the gut

New research has revealed that an existing agent used in the oral drug formulation process may boost the delivery across the gut wall of an injectable medication like insulin.

Most patients fear injections and would prefer to take medication by mouth in tablet or liquid form. Additionally, patients are more likely to follow dosing recommendations if oral formulations are taken once a day. 

A challenge for the pharmaceutical industry is to make oral formulations that will allow active ingredients to cross through the gut wall in sufficient quantity to start working.  

French company, Gattefossé is a leading provider of specialty ingredients and formulation solutions for the beauty and health care industries worldwide. Together with scientists in University College Dublin, they have conducted research on Labrafac™, an established solubilising agent.

Labrafac™ increases blood levels of insulin in rats compared to insulin alone when administered as a mixture into the small intestine of rats under anaesthesia (left).  The tissue gives a normal appearance when exposed to Labrafac™ for two hours (right).

The findings of their studies show Labrafac™ can not only help ingredients to dissolve in water but can be used to boost the permeability of peptides like insulin across the gut wall. 

This means that it can be potentially used as a component of capsules or tablets used to administer macromolecules. Labrafac™ joins a list of only 5-6 agents that can be considered due to its well-known toxicology profile. 

Describing the research study, Professor David Brayden, UCD School of Veterinary Medicine and Fellow, UCD Conway Institute said,” We thought that Labrafac™ might increase gut permeability because it contains a high proportion of medium chain fatty acids presented as glycerides. 

We already knew that two of these, sodium caprate (C10) and caprylate (C8), act as enhancers from advanced clinical trials of oral peptide products, some of which made it to market so we figured that this was a possibility.” 

Dr Fiona McCartney, lead author added, “In the laboratory, we examined the movement of peptides across isolated rat gut tissue in the presence of Labrafac™. We then confirmed in the rat gut instillation model that Labrafac™ could boost absorption of insulin when co-administered as a liquid at the gut wall.”  

This research increases the number of permeation enhancer candidates that can be considered for oral dosage forms of payloads that are poorly permeable. Gattefosse will use these findings to advance discussions with the pharmaceutical industry to have Labrafac™ included in oral screening programmes for macromolecules.

The findings are published in the International Journal of Pharmaceutics and available online.  

The research was funded by Gattefosse through a fellowship award to Dr Fiona McCartney during her time as a postdoctoral researcher in the Brayden laboratory. Fiona is currently working as a Research Fellow with Professor Kenneth Dawson on a new bio-inspired particle architecture delivery technologies (Bio-PADT) project. 

Journal Reference    
McCartney F, Caisse P, Dumont C, Brayden DJ. (2024). LabrafacTM MC60 is an efficacious intestinal permeation enhancer for macromolecules: Comparisons with Labrasol® ALF in ex vivo and in vivo rat studies. International Journal of Pharmaceutics 661:124353. doi: 10.1016/j.ijpharm.2024.124353.