In Vitro and In Vivo Evaluation of 3D Printed Capsules with Pressure Triggered Release Mechanism for Oral Peptide Delivery

• Published in: Journal of pharmaceutical sciences 2021-01, Vol.110 (1), p.228-238
• Main Authors: Berg, Staffan, Krause, Julius, Björkbom, Anders, Walter, Katrin, Harun, Said, Granfeldt, Andreas, Janzén, David, Nunes, Sandro Filipe, Antonsson, Malin, Van Zuydam, Natalie, Skrtic, Stanko, Hugerth, Andreas, Weitschies, Werner, Davies, Nigel, Abrahamsson, Bertil, Bergström, Christel A.S.
• Format: Article
• Language: English
• Subjects: beagle dogs; Bioavailability; Chemistry; delivery; Farmakologi och toxikologi; gastric residence time; intestinal-absorption; Macromolecular drug; Macromolecular drug delivery; octreotide; Oral drug delivery; Peptide delivery; Permeation enhancer(s); pharmacokinetics; Pharmacology & Pharmacy; Pharmacology and Toxicology; predicting drug disposition; profiles; tablets
• ISSN: 0022-3549; 1520-6017; 1520-6017
• DOI: 10.1016/j.xphs.2020.10.066

In this study a 3D printed capsule designed to break from the physiological pressures in the antropyloric region was evaluated for its ability to deliver the synthetic octapeptide octreotide in beagle dogs when co-formulated with the permeation enhancer sodium caprate. The pressure sensitive capsules were compared to traditional enteric coated hard gelatin capsules and enteric coated tablets. Paracetamol, which is completely absorbed in dogs, was included in the formulations and used as an absorption marker to give information about the in vivo performance of the dosage forms. The pressure sensitive capsules released drug in 50% of the dogs. In the cases where drug was released, there was no difference in octreotide bioavailability or Cmax compared to the enteric coated dosage forms. When comparing all dosage forms, a correlation was seen between paracetamol Cmax and octreotide bioavailability, suggesting that a high drug release rate may be beneficial for peptide absorption when delivered together with sodium caprate.