New Chemical Forms of an Absorption Enhancer Could Help Make Oral Semaglutide More Effective

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.

Shapira-Furman, Tovi et al.·Molecules (Basel·2024·Preliminary Evidencein vitro
RPEP-09246In vitroPreliminary Evidence2024RETHINKTHC RESEARCH DATABASErethinkthc.com/research

Quick Facts

Study Type
in vitro
Evidence
Preliminary Evidence
Sample
Pharmaceutical formulation development and testing
Participants
Pharmaceutical formulation development and testing

What This Study Found

Three novel SNAC phenolate salts were successfully synthesized and shown to maintain equivalent oral pharmacokinetic performance for semaglutide delivery in vivo.

Key Numbers

Three SNAC salt forms synthesized: SNAC-choline, SNAC-sodium, and SNAC-phosphatidylcholine.

How They Did This

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.

Why This Research 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 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.

What This Study Doesn't 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.

Questions This Raises

  • ?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?

Trust & Context

Key Stat:
3 novel SNAC salts All maintained equivalent oral semaglutide absorption compared to standard SNAC
Evidence Grade:
Preliminary evidence from in vitro synthesis and limited in vivo rat testing. No human data or comparison to commercial Rybelsus formulation.
Study Age:
Published in 2024. Represents current pharmaceutical research on oral peptide delivery.
Original Title:
The Synthesis of SNAC Phenolate Salts and the Effect on Oral Bioavailability of Semaglutide.
Published In:
Molecules (Basel, Switzerland), 29(16) (2024)
Database ID:
RPEP-09246

Evidence Hierarchy

Meta-Analysis / Systematic Review
Randomized Controlled Trial
Cohort / Case-Control
Cross-Sectional / ObservationalSnapshot without intervening
This study
Case Report / Animal Study
What do these levels mean? →

Frequently Asked Questions

What is SNAC and why is it important for oral semaglutide?

SNAC (sodium N-[8-(2-hydroxybenzoyl)amino]caprylate) is an absorption enhancer that helps semaglutide survive digestion and cross the gut lining. It's the key ingredient that makes Rybelsus (oral semaglutide) possible.

Could these new SNAC forms lead to better oral peptide drugs?

Potentially. By creating new chemical variants of SNAC, researchers expand the options for formulating oral peptide drugs. Different salt forms may offer advantages in stability, manufacturing, or absorption for various peptides.

Read More on RethinkPeptides

Cite This Study

RPEP-09246·https://rethinkpeptides.com/research/RPEP-09246

APA

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

MLA

Shapira-Furman, Tovi, et al. "The Synthesis of SNAC Phenolate Salts and the Effect on Oral Bioavailability of Semaglutide.." Molecules (Basel, 2024. https://doi.org/10.3390/molecules29163909

RethinkPeptides

RethinkPeptides Research Database. "The Synthesis of SNAC Phenolate Salts and the Effect on Oral..." RPEP-09246. Retrieved from https://rethinkpeptides.com/research/shapira-furman-2024-the-synthesis-of-snac

Access the Original Study

Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.

This study breakdown was produced by the RethinkPeptides research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.