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- Section Writer: Dr. Om J Lakhani
- Section Editor: Dr. Om J Lakhani

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• Q. What exactly is SNAC ?
  • It is an intestinal "permeation enhancer"
  • It is also called Salcaprozate sodium
  • It is a fatty acid derivative
  • This does following things:
    • Increases the pH around the tablet
      • protect the tablet from degradation by pepsin
    • creates monomers which helps it to easily absorb
    • induces membrane fluidization and surface epithelial sloughing in the gastric mucosa which helps in absorption of the drug
• Q. SNAC is used for what type of drugs ?
  • It is mainly used for hydrophilic drugs
• Q. Which other drugs in the past have used SNAC ?
  • Vitamin B12
  • Ibradronate
• Q. Which drugs in future are likely to use SNAC ?
  • Calcitonin
  • Octreotide
  • Oral PTH
• Q. In which conditions would you not use SNAC ?
  • "A conservative approach would suggest that PE-containing formulations should not be prescribed for patients with inflammatory bowel disease, irritable bowel syndrome or coeliac disease"
• Q. Which 5 peptides are marketed for oral delivery at present ?
  • 
• Q. What is bioavailablity of Oral semaglutide ?
  • 0.5-1% only !
• Q. What is the half life of Semaglutide ?
  • 160 hours
• Q. What are the challenges for oral delivery of peptides ?
  • 
• Q. What are the mechanisms by which oral delivery of peptides can be improved ?
  • 
• Q. What is the difference between a peptide and a protein ?
  • Peptides are generally considered to be short chains of two or more amino acids. Meanwhile, proteins are long molecules made up of multiple peptide subunits, and are also known as polypeptides
• Q. What is the challenge with oral insulin from point of view of the pH of the GI tract ?
  • "Insulin dissolves in dilute acid but not at neutral pH, which could manifest as poor dissolution in the small intestine"
  • Peptides that have a MW >6000 Da do not have any appreciable intestinal permeability when delivered orally, this makes insulin (5808 Da) especially challenging, with difficulty decreasing in the order of teriparatide (4118 Da) > exenatide (4187 Da) > sCT (3532 Da) > octreotide (1019 Da).
• Q. Amongst the various mechanisms of GI absorption shown below, what it the mechanism followed by SNAC ?
  • 
  • SNAC has a transcellular absorption
• Q. What is the brand name of Vitamin B12 pills having SNAC ?
  • Eligen B12
• Q. What are the concerns with the use of permeation enhances like SNAC ?
  • "There are theoretical concerns that PE-based oral peptide formulations that open TJs might be too toxic due to nonspecific absorption of bystanders (e.g 80](https://www.tandfonline.com/doi/full/10.1080/17425247.2021.1942838#)]) or that the presence of excipients and food emulsifiers might initiate autoimmune disease 81](https://www.tandfonline.com/doi/full/10.1080/17425247.2021.1942838#)].
  • The clinical trials for oral octreotide, however, provided more than 13 months of data on several hundred subjects and there was no evidence that TPE® encouraged absorption of microorganisms or lipopolysaccharide fragments.
  • This conclusion also applied to the use of SNAC in RYBELSUS®. More information on this topic may become apparent during post-marketing surveillance of both products.
  • It remains unclear whether amphiphilic excipient-induced changes in the gut microbiome can be linked to human pathology 82](https://www.tandfonline.com/doi/full/10.1080/17425247.2021.1942838#),83], but more data on this controversial topic can be expected because of the expanding amount of microbiome research and because many emulsifiers and other surfactants are used as excipients and food additives
• Q. Oral semaglutide is absorbed from Stomach or intestine ?
  • it is absorbed from the stomach and not intestine
  • It does two thing:
    • 1. Neutralize the pH in the stomach
    • 2. protects from enzymatic degradation (reduces pepsin activity)
• Q. What are the three most important variables impacting Oral semaglutide exposure ?
  • 1. Period of fasting
    • Longer the better
  • 2. Amount of water intake
    • Lesser the better
  • 3. Body weight
• Q. What is within subject variablity of Oral semaglutide ?
  • 137% before steady state is achieved
  • 33% after steady state is achieved