Researchers created novel phenolate salt versions of SNAC (the absorption enhancer used in oral semaglutide) that maintained drug absorption while potentially expanding the toolkit for oral peptide delivery.
3 novel SNAC saltsAll maintained equivalent oral semaglutide absorption compared to standard SNAC
What the researchers found
Three novel SNAC phenolate salts were successfully synthesized and shown to maintain equivalent oral pharmacokinetic performance for semaglutide delivery in vivo.
Why it matters
Oral delivery is a major challenge for peptide drugs, and SNAC is one of only a few proven absorption enhancers. Expanding the range of SNAC-based enhancers could lead to better formulations with improved stability, absorption, or patient tolerability.
The numbers in context
Three SNAC salt forms synthesized: SNAC-choline, SNAC-sodium, and SNAC-phosphatidylcholine.
How the study worked
Chemical synthesis of SNAC phenolate salts confirmed via 1H-NMR, FTIR, and elemental analysis. In vivo oral pharmacokinetic testing in rats comparing new salts to standard SNAC for semaglutide delivery.
Who was studied
Pharmaceutical formulation development and testing
What this study cannot tell us
Only tested in rats, so human pharmacokinetics may differ. The study demonstrated non-inferiority to standard SNAC but did not show clear superiority. Long-term safety of the new salt forms was not assessed.
How to read the evidence
Preliminary evidence from in vitro synthesis and limited in vivo rat testing. No human data or comparison to commercial Rybelsus formulation.
When this study was published
Published in 2024. Represents current pharmaceutical research on oral peptide delivery.
The bigger picture
Most peptide drugs require injection because they are destroyed in the digestive system. The success of oral semaglutide has shown that absorption enhancers like SNAC can overcome this barrier. This work expands the chemical space of SNAC-based enhancers, which could improve future oral formulations for semaglutide and other therapeutic peptides.
Questions still open
- Could any of these SNAC phenolate salts improve oral bioavailability beyond what standard SNAC achieves?
- How do these new salt forms perform with other peptide drugs besides semaglutide?
- What is the stability profile of these salts under various storage conditions?
Common questions
What is SNAC and why is it important for oral semaglutide?
Could these new SNAC forms lead to better oral peptide drugs?
Read the original research
The Synthesis of SNAC Phenolate Salts and the Effect on Oral Bioavailability of Semaglutide.
Molecules (Basel, Switzerland), 29(16)
Citation
Shapira-Furman, Tovi; Bar-Hai, Ayala; Hoffman, Amnon; Domb, Abraham J. (2024). The Synthesis of SNAC Phenolate Salts and the Effect on Oral Bioavailability of Semaglutide.. Molecules (Basel, Switzerland), 29(16). https://doi.org/10.3390/molecules29163909