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SNAC: A Stepping Stone to Oral Semaglutide

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Salcaprozate sodium (SNAC) is the sodium salt form of salcaprozate. It is used in the treatment of gastrointestinal disorders, especially gastrointestinal disorders caused by the malabsorption of dicarbonate-phosphate compounds. SNAC can also promote the absorption of drugs in gastrointestinal epithelial cells, and effectively cope with the obstacles to the absorption of oral peptide drugs, for instance Semaglutide.


Absorption of oral dose peptides by intestine is challenging due to the physiological effects of the gastrointestinal tract. Ingested peptides or proteins are broken down into amino acids by ph-sensitive proteases, which are then transported to the mucosa by the translocater. Large molecules of carbohydrates or lipids are decomposed into small molecules to promote intestinal absorption. The intestinal epithelium has the function of recognizing and absorbing bacteria, viruses and other pathogens. So complex cellular and mucus barriers are formed to limit the entry of foreign or harmful substances. Therefore, unfortunately, exogenous peptides or protein drugs are restricted to penetrate the intestinal epithelium and enter the circulation. In this case, SNAC and its related compounds are used as Permeation enhancers to deal with this problem.

The mechanism that SNAC promotes the absorption of Active pharmaceutical ingredient (API) is still not fully understood. It is generally believed that SNAC improves the membrane permeability of gastrointestinal epithelial cells may be related to membrane perturbation, membrane fluidization, and changes in API solubility. It also may improve transcellular permeability by increasing its hydrophobic role through non-covalent bond binding to API.


The successful preparation of semaglutide tablets depends on its co-formulation with SNAC.

  • SNAC promotes the monosomy of semaglutide, making it more permeable. For semaglutide molecules, most semaglutide exists in the form of oligomers in the stomach; However, SNAC triggered a change in polarity of the solution containing the dissolved tablet, weakening the hydrophobic interaction necessary for oligomerization.
  • Since SNAC is lipophilic, it efficiently inserts into the cell membrane of the gastric epithelium, altering the intrinsic integrity of cholesterol phospholipids and proteins, which in turn affect the fluidity of the cell membrane. It was confirmed that SNAC enhances the intracellular uptake of semaglutide by gastric epithelial cells, thus supporting the notion that SNAC promotes transcellular transport of semaglutide.
  • SNAC can effectively increase the local pH value around the semaglutide molecule in the stomach, prevent the degradation of peptides by pepsin, and make semaglutide penetrate the gastric mucosa and be absorbed into blood by the concentration gradient on the surface of the cell membrane.

The use of SNAC is of great significance for oral semaglutide tablets. FarmaSino can provide high purity and high quality SNAC together with Semaglutide API* and intermediates include semaglutide-related fragments, main chains, and side chains of different steps. Please check following links for more information.