Next Article in Journal / Special Issue
Development of a Biphasic-Release Multiple-Unit Pellet System with Diclofenac Sodium Using Novel Calcium Phosphate-Based Starter Pellets
Previous Article in Journal
Biomaterials for the Prevention of Oral Candidiasis Development
Previous Article in Special Issue
Buccal Resveratrol Delivery System as a Potential New Concept for the Periodontitis Treatment
Article

Development and Bio-Predictive Evaluation of Biopharmaceutical Properties of Sustained-Release Tablets with a Novel GPR40 Agonist for a First-in-Human Clinical Trial

1
Research and Development Center, Celon Pharma S.A., Marymoncka 15, 05-052 Kazuń Nowy, Poland
2
Physiolution Polska sp. z o.o., 74 Piłsudskiego St., 50-020 Wrocław, Poland
3
Physiolution GmbH, Walther Rathenau Strasse 49a, 17489 Greifswald, Germany
4
Department of Physical Pharmacy and Pharmacokinetics, Poznan University of Medical Sciences, 6 Święcickiego St., 60-781 Poznań, Poland
*
Author to whom correspondence should be addressed.
Academic Editor: Peter Timmins
Pharmaceutics 2021, 13(6), 804; https://doi.org/10.3390/pharmaceutics13060804
Received: 30 April 2021 / Revised: 20 May 2021 / Accepted: 25 May 2021 / Published: 28 May 2021
Sustained-release (SR) formulations may appear advantageous in first-in-human (FIH) study of innovative medicines. The newly developed SR matrix tablets require prolonged maintenance of API concentration in plasma and should be reliably assessed for the risk of uncontrolled release of the drug. In the present study, we describe the development of a robust SR matrix tablet with a novel G-protein-coupled receptor 40 (GPR40) agonist for first-in-human studies and introduce a general workflow for the successful development of SR formulations for innovative APIs. The hydrophilic matrix tablets containing the labeled API dose of 5, 30, or 120 mg were evaluated with several methods: standard USP II dissolution, bio-predictive dissolution tests, and the texture and matrix formation analysis. The standard dissolution tests allowed preselection of the prototypes with the targeted dissolution rate, while the subsequent studies in physiologically relevant conditions revealed unwanted and potentially harmful effects, such as dose dumping under an increased mechanical agitation. The developed formulations were exceptionally robust toward the mechanical and physicochemical conditions of the bio-predictive tests and assured a comparable drug delivery rate regardless of the prandial state and dose labeled. In conclusion, the introduced development strategy, when implemented into the development cycle of SR formulations with innovative APIs, may allow not only to reduce the risk of formulation-related failure of phase I clinical trial but also effectively and timely provide safe and reliable medicines for patients in the trial and their further therapy. View Full-Text
Keywords: GPR40 agonist; sustained-release tablets; first in human clinical trials; simulation of gastrointestinal passage; biorelevant dissolution testing; stress test device GPR40 agonist; sustained-release tablets; first in human clinical trials; simulation of gastrointestinal passage; biorelevant dissolution testing; stress test device
Show Figures

Graphical abstract

MDPI and ACS Style

Juszczyk, E.; Kisło, K.; Żero, P.; Tratkiewicz, E.; Wieczorek, M.; Paszkowska, J.; Banach, G.; Wiater, M.; Hoc, D.; Garbacz, G.; Sczodrok, J.; Danielak, D. Development and Bio-Predictive Evaluation of Biopharmaceutical Properties of Sustained-Release Tablets with a Novel GPR40 Agonist for a First-in-Human Clinical Trial. Pharmaceutics 2021, 13, 804. https://doi.org/10.3390/pharmaceutics13060804

AMA Style

Juszczyk E, Kisło K, Żero P, Tratkiewicz E, Wieczorek M, Paszkowska J, Banach G, Wiater M, Hoc D, Garbacz G, Sczodrok J, Danielak D. Development and Bio-Predictive Evaluation of Biopharmaceutical Properties of Sustained-Release Tablets with a Novel GPR40 Agonist for a First-in-Human Clinical Trial. Pharmaceutics. 2021; 13(6):804. https://doi.org/10.3390/pharmaceutics13060804

Chicago/Turabian Style

Juszczyk, Ewelina, Kamil Kisło, Paweł Żero, Ewa Tratkiewicz, Maciej Wieczorek, Jadwiga Paszkowska, Grzegorz Banach, Marcela Wiater, Dagmara Hoc, Grzegorz Garbacz, Jaroslaw Sczodrok, and Dorota Danielak. 2021. "Development and Bio-Predictive Evaluation of Biopharmaceutical Properties of Sustained-Release Tablets with a Novel GPR40 Agonist for a First-in-Human Clinical Trial" Pharmaceutics 13, no. 6: 804. https://doi.org/10.3390/pharmaceutics13060804

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop