Supersaturated Lipid-Based Formulations to Enhance the Oral Bioavailability of Venetoclax
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Authors
Koehl, Niklas
Author (Corporation)
Publication date
18.06.2020
Typ of student thesis
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Type
01A - Journal article
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Parent work
Pharmaceutics
Special issue
DOI of the original publication
Series
Series number
Volume
12
Issue / Number
6
Pages / Duration
564
Patent number
Publisher / Publishing institution
Elsevier
Place of publication / Event location
Edition
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Abstract
Increasing numbers of beyond Rule-of-Five drugs are emerging from discovery pipelines, generating a need for bio-enabling formulation approaches, such as lipid-based formulations (LBF), to ensure maximal in vivo exposure. However, many drug candidates display insufficient lipid solubility, leading to dose-loading limitations in LBFs. The aim of this study was to explore the potential of supersaturated LBFs (sLBF) for the beyond Rule-of-Five drug venetoclax. Temperature-induced sLBFs of venetoclax were obtained in olive oil, Captex® 1000, Peceol® and Capmul MCM®, respectively. A Peceol®-based sLBF displayed the highest drug loading and was therefore evaluated further. In vitro lipolysis demonstrated that the Peceol®-based sLBF was able to generate higher venetoclax concentrations in the aqueous phase compared to a Peceol®-based suspension and an aqueous suspension. A subsequent bioavailability study in pigs demonstrated for sLBF a 3.8-fold and 2.1-fold higher bioavailability compared to the drug powder and Peceol®-based suspension, respectively. In conclusion, sLBF is a promising bio-enabling formulation approach to enhance in vivo exposure of beyond Rule-of-Five drugs, such as venetoclax. The in vitro lipolysis results correctly predicted a higher exposure of the sLBF in vivo. The findings of this study are of particular relevance to pre-clinical drug development, where maximum exposure is required.
Keywords
SEDDS, Super-SNEDDS, amorphous solubility, landrace pigs, lipid suspensions, lipid-based formulation, self-emulsifying drug delivery system, supersaturated lipid-based formulations, supersaturation, venetoclax
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ISBN
ISSN
0378-5173
1873-3476
1873-3476
Language
English
Created during FHNW affiliation
Yes
Strategic action fields FHNW
Publication status
Published
Review
Peer review of the complete publication
Open access category
License
Citation
Koehl, N., & Kuentz, M. (2020). Supersaturated Lipid-Based Formulations to Enhance the Oral Bioavailability of Venetoclax. Pharmaceutics, 12(6), 564. https://doi.org/10.3390/pharmaceutics12060564