Journal of controlled release : official journal of the Controlled Release SocietyNov 20, 2024

Salcaprozate-based ionic liquids may improve stomach delivery of GLP-1: Understanding how they work in living bodies

GLP-1 Therapies Weekly Brief ↗PubMed ↗DOI ↗

Updated Jan 20, 2026

Abstract

The new salcaprozate-based ionic liquid formulation, choline salcaprozate (CHONAC), showed faster absorption of a glucagon-like peptide-1 analogue in vivo compared to reference formulations.

In vitro studies indicated that the CHONAC formulation accommodated a higher concentration of permeation enhancer in the same volume compared to traditional tablets.
The release of the active pharmaceutical ingredient and permeation enhancer from the CHONAC formulation was faster than that from the reference tablet.
In vivo evaluations demonstrated that the CHONAC formulation led to quicker absorption of the peptide in rats and anesthetized dogs.
However, in awake dogs, the overall exposure to the peptide from the CHONAC formulation was lower than that from the tablet reference, likely due to gastric physiology effects.
Repeated dosing studies in anesthetized dogs suggested the potential for sustained peptide absorption with a consistent rate, highlighting the importance of formulation interaction with the stomach epithelium.

Simplified

Oral delivery of peptides requires formulations with high concentrations of permeation enhancer (PE) to promote absorption, and often necessitates fasting time between dosing and food ingestion. Improved formulations promoting a more rapid absorption would increase convenience of use but requires a faster onset of action. We have developed a salcaprozate-based ionic liquid (IL) formulation, namely choline salcaprozate (CHONAC), for oral delivery of a glucagon-like peptide-1 (GLP-1) analogue via gastric absorption. In vitro studies confirmed the higher amount of PE accommodated in the same volume of dosage form as well as faster release of the active pharmaceutical ingredient (API) and PE compared to the tablet reference. Storage stability of the CHONAC formulation was demonstrated for up to 3 weeks at 4 °C. The peptide absorption efficacy of the IL formulation was first evaluated in vivo in rats and anesthetized dogs, showing a faster absorption compared to the reference formulations. In awake dogs, while the CHONAC formulation still enabled earlier API absorption, its overall exposure was inferior to the tablet reference. This was attributed mostly to the gastric physiology, causing formulation dilution in the presence of additional fluid as well as fast transit of liquids into the duodenum, where peptides liable to proteolytic degradation such as the one used in this study showed a negligible absorption, potentially also due to a lower permeation-enhancing capability of CHONAC in the duodenal region. Exploring these issues, an in vivo study in anesthetized dogs involving repeated dosing of a liquid salcaprozate-based formulation in the stomach revealed the potential to sustain peptide absorption throughout the dosing period with a constant absorption rate. In conclusion, combining the advantages of high PE amounts and fast onset of action provided by the IL formulation, and ensuring a prolonged interaction of peptide and PE at a relevant concentration with the stomach epithelium, are necessary to enhance oral peptide bioavailability via gastric delivery.

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Salcaprozate-based ionic liquids may improve stomach delivery of GLP-1: Understanding how they work in living bodies

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