Targeted oral peptide delivery using multi-unit particulates: Drug and permeation enhancer layering approach

Puneet Tyagi; Ruchit Trivedi; Sergei Pechenov; Chandresh Patel; Jefferson Revell; Sarah Wills; Yue Huang; Anton I Rosenbaum; J Anand Subramony

doi:10.1016/j.jconrel.2021.09.002

Targeted oral peptide delivery using multi-unit particulates: Drug and permeation enhancer layering approach

J Control Release. 2021 Oct 10:338:784-791. doi: 10.1016/j.jconrel.2021.09.002. Epub 2021 Sep 6.

Authors

Puneet Tyagi¹, Ruchit Trivedi², Sergei Pechenov¹, Chandresh Patel¹, Jefferson Revell³, Sarah Wills⁴, Yue Huang⁵, Anton I Rosenbaum⁵, J Anand Subramony⁶

Affiliations

¹ Dosage Form Design and Development, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA.
² Bioduro, San Diego, CA, USA.
³ Antibody Discovery & Protein Engineering, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK.
⁴ Bioscience Metabolism, Research and Early Development, Cardiovascular, Renal and Metabolism, Biopharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA.
⁵ Integrated Bioanalysis, Clinical Pharmacology and Quantitative Pharmacology, Clinical Pharmacology & Safety Sciences, R&D, AstraZeneca, South San Francisco, CA, USA.
⁶ Antibody Discovery and Protein Engineering, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA. Electronic address: anand.subramony@astrazeneca.com.

PMID: 34499981
DOI: 10.1016/j.jconrel.2021.09.002

Abstract

Oral delivery of peptides is a challenge due to their instability and their limited transport and absorption characteristics within the gastrointestinal tract. In this work, we used layering techniques in a fluidized bed dryer to create a configuration in which the active peptide, permeation enhancers, and polymers are coated to control the release of the peptide. Formulations were developed to disintegrate at pH values of 5.5 and 7.0. In addition, sustained-release or mucoadhesive polymers were coated to trigger release at a desired site in the gastrointestinal tract. Dissolution studies with a USP Type I (basket) apparatus confirmed the duration of release. Pharmacokinetic studies were performed in beagle dogs to evaluate bioavailability. A high-disintegration pH was found to be advantageous in enhancing bioavailability.

Keywords: Dissolution; Dog; Multi-unit particulate system; Oral peptide delivery; Sustained delivery.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Administration, Oral
Animals
Biological Availability
Dogs
Peptides
Pharmaceutical Preparations*
Polymers
Solubility

Substances

Peptides
Pharmaceutical Preparations
Polymers