Salcaprozate Sodium (SNAC): A Key Enabler for Oral Drug Delivery

Introduction

Salcaprozate Sodium, more commonly known in pharmaceutical circles by its acronym SNAC, is a critically important absorption enhancer used to facilitate the oral delivery of

poorly permeable active pharmaceutical ingredients (APIs). Its CAS (Chemical Abstracts Service) registry number is 203787-91-1. This molecule has garnered significant

attention for its role in revolutionizing how certain drugs, particularly peptides and macromolecules, are administered, moving away from injections toward more

patient-friendly oral tablets.

Chemical Profile

· Chemical Name: Sodium N-(8-(2-hydroxybenzoyl) amino) caprylate

· Synonyms: SNAC, Salcaprozate Sodium

· CAS Number: 203787-91-1

· Molecular Formula: C₁₅H₁₉NNaO₄

· Molecular Weight: 300.30 g/mol

SNAC is an organic sodium salt derived from salicylic acid and caprylic acid. Its structure is uniquely designed to be amphiphilic, meaning it possesses both hydrophilic

(water-attracting) and hydrophobic (water-repelling) regions. This property is fundamental to its mechanism of action.

Mechanism of Action: How SNAC Works The primary challenge with oral delivery of large molecules like peptides (e.g., insulin, semaglutide) or highly insoluble drugs is the

harsh environment of the gastrointestinal (GI) tract and the low permeability of the intestinal epithelium. SNAC addresses this through a multi-faceted mechanism:

1. Permeation Enhancement: SNAC's amphiphilic nature allows it to interact with and temporarily disrupt the phospholipid bilayer of cell membranes in the GI tract. This action

increases the paracellular (between cells) and transcellular (through cells) permeability, creating a transient "window" for the co-administered drug to pass through into the

bloodstream.

2. Buffering Effect: SNAC has an intrinsic ability to raise the local micro-environmental pH immediately surrounding the drug. For drugs that are susceptible to degradation in

the highly acidic stomach, this buffering effect offers protection, increasing their stability and chances of survival until absorption.

3. Solubilization: For hydrophobic (fat-soluble) drugs, SNAC can act as a surfactant, helping to solubilize the drug and improve its dissolution in the GI fluids, which is a critical

first step for absorption.

It is crucial to note that SNAC's action is localized and transient. It does not cause widespread or permanent damage to the intestinal lining, making it a relatively safe

excipient for chronic use.

Primary Applications and landmark Use The most prominent and successful application of SNAC is in the groundbreaking oral formulation of the glucagon-like peptide-1

(GLP-1) receptor agonist, semaglutide.

· Product: Rybelsus® (oral semaglutide)

· Indication: Type 2 diabetes

· Significance: Before Rybelsus®, GLP-1 agonists were exclusively available as subcutaneous injections. The tablet formulation, enabled by SNAC, was a monumental

achievement in pharmaceuticals, offering a highly effective and convenient oral alternative for millions of patients.

SNAC is also being extensively researched for its potential to enable the oral delivery of other biologics, including heparin, insulin, and various other peptides and proteins

that were previously thought to be "undruggable" via the oral route.

Safety and Regulatory Status SNAC is classified as an inactive ingredient or excipient. It has undergone rigorous toxicological studies and has been deemed safe for human

use at the approved dosages. The U.S. Food and Drug Administration (FDA) and other global regulatory agencies have approved its use in the Rybelsus® tablet. Its safety

profile is well-established, with no significant systemic absorption of SNAC itself—it performs its function locally in the GI tract and is subsequently excreted.

Future Outlook The success of SNAC with oral semaglutide has validated the concept of absorption-enhancing technology. It has opened new avenues for research and

development in oral drug delivery. Scientists are exploring:

· Other delivery-enhancing agents with similar or improved properties.

· Combinations of enhancers for a synergistic effect.

· The application of SNAC technology for a wider range of biologic drugs, potentially expanding treatment options for various diseases.

Conclusion Salcaprozate Sodium (SNAC, CAS 203787-91-1) is far more than a simple chemical compound; it is a pivotal technological innovation in pharmaceutical science.

By overcoming the fundamental biological barriers of the GI tract, SNAC has successfully bridged the gap between injectable biologics and oral medications. Its role in

enabling the first oral GLP-1 therapy has made it a cornerstone of modern drug delivery, promising a future where more effective and convenient treatments are accessible

to patients worldwide.