The combined effect of permeation enhancement and proteolysis inhibition on the systemic exposure of orally administrated peptides: Salcaprozate sodium, soybean trypsin inhibitor, and teriparatide study in pigs

Gregory Burshtein; Constantin Itin; Jonathan C Y Tang; Hillel Galitzer; William D Fraser; Phillip Schwartz

doi:10.1016/j.ijpx.2021.100097

The combined effect of permeation enhancement and proteolysis inhibition on the systemic exposure of orally administrated peptides: Salcaprozate sodium, soybean trypsin inhibitor, and teriparatide study in pigs

Int J Pharm X. 2021 Oct 8:3:100097. doi: 10.1016/j.ijpx.2021.100097. eCollection 2021 Dec.

Authors

Gregory Burshtein¹, Constantin Itin¹, Jonathan C Y Tang², Hillel Galitzer¹, William D Fraser^{2

3}, Phillip Schwartz¹

Affiliations

¹ Entera Bio Ltd., Jerusalem BioPark, Jerusalem 9112002, Israel.
² Bioanalytical Facility, Biomedical Research Centre, Norwich Medical School, Faculty of Medicine and Health Sciences, University of East Anglia, Norwich, UK.
³ Departments of Endocrinology and Clinical Biochemistry, Norfolk and Norwich University Hospital, Norwich, UK.

Abstract

Oral delivery of peptides and proteins is hindered by their rapid proteolysis in the gastrointestinal tract and their inability to permeate biological membranes. Various drug delivery approaches are being investigated and implemented to overcome these obstacles. In the discussed study conducted in pigs, an investigation was undertaken to assess the effect of combination of a permeation enhancer - salcaprozate sodium, and a proteolysis inhibitor - soybean trypsin inhibitor, on the systemic exposure of the peptide teriparatide, following intraduodenal administration. Results demonstrate that this combination achieves significantly higher Cmax and AUC (~10- and ~20-fold respectively) compared to each of these methodologies on their own. It was thus concluded that an appropriate combination of different technological approaches may considerably contribute to an efficient oral delivery of biological macromolecules.

Keywords: GIT, gastrointestinal tract; Oral delivery; PK, pharmacokinetics; PTH, parathyroid hormone; Permeation enhancer; Pharmacokinetics; SBTI, soybean trypsin inhibitor; SNAC; SNAC, salcaprozate sodium; Salcaprozate sodium; Soybean trypsin inhibitor; Teriparatide; hPTH(1–34), teriparatide.