Profound effects of gastric secretion rate variations on the precipitation of erlotinib in duodenum – An in vitro investigation

Yiwang Guo; Changquan Calvin Sun

doi:10.1016/j.ijpharm.2022.121722

Profound effects of gastric secretion rate variations on the precipitation of erlotinib in duodenum – An in vitro investigation

Yiwang Guo, Changquan Calvin Sun

Pharmaceutics

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1 Scopus citations

Abstract

Using an artificial stomach and duodenum (ASD), we investigated the pH-dependent precipitation of erlotinib (ERL) during dissolution in the gastrointestinal (GI) tract by varying the rate of gastric fluid secretion (RGFS). Results show that decreasing RGFS from 2.5 to 0.5 mL/min leads to an increased degree of supersaturation in the duodenum fluid due to elevated pH, resulting in precipitation of ERL and a reduced area under the curve (AUC) of the concentration – time profiles from 14,000 to 3,000 (μg‧min)/mL. Such a change in AUC is expected to lower the bioavailability of ERL, a BCS II drug, in patients with a low RGFS. This example demonstrates the potential use of ASD as an effective tool for guiding the efficient development of robust tablet formulations by better understanding the impact of GI tract pH on the fate of drugs in the duodenal fluid.

Original language	English (US)
Article number	121722
Journal	International journal of pharmaceutics
Volume	619
DOIs	https://doi.org/10.1016/j.ijpharm.2022.121722
State	Published - May 10 2022

Bibliographical note

Funding Information:
We thank Dr. Michael Hawley for guidance with setting up the artificial stomach and duodenum apparatus. Y.G. thanks the Graduate School of the University of Minnesota for a Doctoral Dissertation Fellowship (2020 – 2021) and the Department of Pharmaceutics, University of Minnesota for a David J.W. Grant & Marilyn J. Grant Fellowship in Physical Pharmacy (2020 – 2021). C.C.S. thanks the National Science Foundation for support through the Industry University Collaborative Research Center grant IIP-2137264, Center for Integrated Materials Science and Engineering for Pharmaceutical Products (CIMSEPP).

Publisher Copyright:
© 2022 Elsevier B.V.

Keywords

Artificial stomach and duodenum
Biorelevant dissolution
Erlotinib HCl
pH
Precipitation

PubMed: MeSH publication types

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abstract = "Using an artificial stomach and duodenum (ASD), we investigated the pH-dependent precipitation of erlotinib (ERL) during dissolution in the gastrointestinal (GI) tract by varying the rate of gastric fluid secretion (RGFS). Results show that decreasing RGFS from 2.5 to 0.5 mL/min leads to an increased degree of supersaturation in the duodenum fluid due to elevated pH, resulting in precipitation of ERL and a reduced area under the curve (AUC) of the concentration – time profiles from 14,000 to 3,000 (μg‧min)/mL. Such a change in AUC is expected to lower the bioavailability of ERL, a BCS II drug, in patients with a low RGFS. This example demonstrates the potential use of ASD as an effective tool for guiding the efficient development of robust tablet formulations by better understanding the impact of GI tract pH on the fate of drugs in the duodenal fluid.",

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Profound effects of gastric secretion rate variations on the precipitation of erlotinib in duodenum – An in vitro investigation

Abstract

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