Elsevier

Drug Discovery Today

Volume 25, Issue 8, August 2020, Pages 1374-1388
Drug Discovery Today

Review
Keynote
pH-dependent ileocolonic drug delivery, part II: preclinical evaluation of novel drugs and novel excipients

https://doi.org/10.1016/j.drudis.2020.06.012Get rights and content
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Highlights

  • Novel drugs and novel excipients have to be evaluated in laboratory animals.

  • Different laboratory animals have been used to verify ileocolonic drug delivery.

  • The rabbit has gastrointestinal pH values comparable to those in humans.

  • Novel drugs are best tested by non-invasive imaging techniques with blood sampling.

  • Novel excipients are best tested by the theophylline-sulfasalazine method.

Safety issues require that novel drugs and novel excipients, formulated in pH-dependent ileocolonic drug delivery systems, are tested in appropriate animal species before they are evaluated in humans. In a literature search, we found that, of the most frequently used laboratory animal species, the rabbit is the best choice. Its gastrointestinal (GI) pH values most resembles those in humans. In cases where rabbits cannot be used, pigs, dogs, and rats can serve as an alternative provided that GI pH values of individual animals are checked. Various methods to investigate the performance of ileocolonic drug delivery systems are available. We recommend testing novel drugs with non-invasive imaging techniques in combination with plasma sampling, whereas novel excipients are best tested with the theophylline-sulfasalazine method.

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Annemarie Broesder received her MSc in pharmacy from the University of Groningen (The Netherlands). Currently, she is pursuing her PhD in the Department of Pharmaceutical Technology and Biopharmacy at the University of Groningen under the supervision of Prof. Dr H.W. Frijlink and Dr. W.L.J. Hinrichs. Her research focuses on oral pH-dependent ileocolonic drug delivery and the suitability of these systems for different dosage forms.

Wouter L.J. Hinrichs studied chemistry at the University of Groningen and received his PhD from the University of Twente (The Netherlands) in 1993. Thereafter, he worked as a postdoc in the University of Twente and Utrecht University (The Netherlands) until 1998. Since then, he has been an assistant professor at the Department of Pharmaceutical Technology and Biopharmacy at Groningen Research Institute of Pharmacy (The Netherlands). One of his research interests is oral dosage forms. He has (co-)authored more than 140 original articles in peer-reviewed journals and book chapters.

Henderik W. Frijlink has been a professor and chairman of the Department of Pharmaceutical Technology and Biopharmacy at the Groningen Research Institute of Pharmacy since 1998. He is interested in solid oral dosage forms, their technological and biopharmaceutical aspects and gastrointestinal targeting strategy. Further interests of his current research are technical and biopharmaceutical aspects of pulmonary drug delivery. The formulation of biopharmaceuticals, such as peptides, proteins, vaccines, and gene-based products, using stabilizing sugar glasses is a further research topic in his department. He has published over 200 peer-reviewed papers in the field.