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. 2021 Oct 8:3:100097.
doi: 10.1016/j.ijpx.2021.100097. eCollection 2021 Dec.

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  1 , Constantin Itin  1 , Jonathan C Y Tang  2 , Hillel Galitzer  1 , William D Fraser  2   3 , Phillip Schwartz  1
Affiliations

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 et al. Int J Pharm X. .

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.

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Conflict of interest statement

None.

Figures

Unlabelled Image
Graphical abstract
Fig. 1
Fig. 1
Delivery of the formulation in the form of a dry granulate (indicated by an arrow) to the duodenum by a custom-made endoscope-based device. The size bar shows the dimensions of the administered granules.
Fig. 2
Fig. 2
Teriparatide plasma concentration vs. time plot (mean ± SEM) following administration of formulations in the form of a dry granulate containing 0.75 mg teriparatide acetate (0.69 mg teriparatide as a free base) directly to the duodenum of female pigs by a custom-made endoscope-based device; SNAC – salcaprozate sodium, SBTI – soybean trypsin inhibitor, hPTH(1–34) – teriparatide (as acetate); SNAC/SBTI/hPTH(1–34) formulation: n = 5; SNAC/hPTH(1–34) formulation: n = 5; SBTI/hPTH(1–34) formulation: n = 4.
See this image and copyright information in PMC

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