Fabrication of 3D-printed octreotide acetate-loaded oral solid dosage forms by means of semi-solid extrusion printing

Aikaterini-Theodora Chatzitaki; Georgios Eleftheriadis; Konstantinos Tsongas; Dimitrios Tzetzis; Apostolos Spyros; Ioannis S Vizirianakis; Dimitrios G Fatouros

doi:10.1016/j.ijpharm.2022.122569

Fabrication of 3D-printed octreotide acetate-loaded oral solid dosage forms by means of semi-solid extrusion printing

Int J Pharm. 2023 Feb 5:632:122569. doi: 10.1016/j.ijpharm.2022.122569. Epub 2022 Dec 30.

Authors

Aikaterini-Theodora Chatzitaki¹, Georgios Eleftheriadis², Konstantinos Tsongas³, Dimitrios Tzetzis³, Apostolos Spyros⁴, Ioannis S Vizirianakis⁵, Dimitrios G Fatouros¹

Affiliations

¹ Laboratory of Pharmaceutical Technology, Department of Pharmacy, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece.
² Laboratory of Pharmaceutical Technology, Department of Pharmacy, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece. Electronic address: gkelefth@pharm.auth.gr.
³ Digital Manufacturing and Materials Characterization Laboratory, School of Science and Technology, International Hellenic University, 57001 Thermi, Greece.
⁴ NMR Laboratory, Department of Chemistry, University of Crete, Voutes Campus, P.O. Box 2208, GR-71003 Heraklion, Crete, Greece.
⁵ Laboratory of Pharmacology, School of Pharmacy, Faculty of Health Sciences, Aristotle University of Thessaloniki, GR-54124 Thessaloniki, Greece; Department of Life & Health Sciences, School of Sciences and Engineering, University of Nicosia, Nicosia 1700, Cyprus.

PMID: 36592893
DOI: 10.1016/j.ijpharm.2022.122569

Abstract

Semi-solid extrusion (SSE) 3D printing technology was utilized for the encapsulation of octreotide acetate (OCT) into 3D-printed oral dosage forms in ambient conditions. The inks and the OCT-loaded 3D-printed oral dosage forms were characterized by means of rheology, Fourier-transform infrared (FTIR) spectroscopy and Nuclear Magnetic Resonance (NMR). In vitro studies demonstrated that the formulations released OCT in a controlled manner. The application of these formulations to Caco-2 cell monolayers revealed their capability to induce the transient opening of tight junctions in a reversible manner as evidenced by Transepithelial Resistance (TEER) measurements. Cellular assays (CCK-8 assay) demonstrated the viability of intestinal cells in the presence of these formulations. The in vitro transport studies across Caco-2 monolayers demonstrated the ability of these formulations to enhance the OCT uptake across the cell monolayer over time due to opening of the tight junctions.

Keywords: 3D printing; Cytotoxicity; NMR analysis; Octreotide; Oral peptide delivery; Semi-solid extrusion.

MeSH terms

Caco-2 Cells
Dosage Forms
Drug Compounding / methods
Drug Liberation
Humans
Octreotide*
Printing, Three-Dimensional*
Technology, Pharmaceutical / methods

Substances

Octreotide
Dosage Forms