Peptide drugs and protein drugs, compared to traditional small molecule drugs, has the following disadvantages:

- Injection is a common route of administration for peptide drugs. The invasive nature lowers the patient compliance.

- Most peptides and protein drugs have short circulation time and thus short half-lives. They are prone to intracellular and extracellular degradation, and renal elimination.

- Higher immunogenicity due to large sizes.

- Low permeability.

For peptide drugs, one development trend is to optimize the drug delivery from the unpleasant injection to oral ingestion. Apart from covalent modifcation such as lipidation seen in approved peptide drugs such as Semaglutide, a class of excipients known as absorption promotor also draws a great attention.

About SNAC

Salcaprozate sodium (SNAC, CAS No. 203787-91-1), first developed by Emisphere in the 1990s, is an oral absorption promoter / permeation enhancer. SNAC is a synthetic N-acetylated amino acid derivatives of salicylic acid, and can be used to overcome the challenges of oral pepetide delivery.

The molecular structure of SNAC

We offer the SNAC of the highest quality and customization. For instance, the D90 can be customized less than 30 microns, although the normal limit is 100 microns and smaller particle sizes may cause operation difficulty. The product has been commercially supplied to CMOs.

For example, Semaglutide (Rybelsus), the first approved oral GLP-1RA formulation, achieved up to 4.2 billion USD sales in 2023 Q1. Part of the success can be attributed to the excipient SNAC. By co-formulating with SNAC, Semaglutide could safely reach the stomach with little enzymatic degradation in the local buffering environment provided by SNAC. In addition, the ionic stength of SNAC reduces hydrophobic interactions and promotes the Semaglutide monomerization. Another possible mechanism of SNAC in increasing the absorption is through an indirect action of SNAC. By incorporting into the lipid membranes, it fluidizes the lipid bilayers and thereby allowing Semaglutide to pass the gastric lining and enter the blood stream.

MOA of SNAC in assisting Semaglutide absorption. src: Aroda, V.R., Blonde, L. & Pratley, R.E. A new era for oral peptides: SNAC and the development of oral semaglutide for the treatment of type 2 diabetes. Rev Endocr Metab Disord 23, 979–994 (2022). https://doi.org/10.1007/s11154-022-09735-8