Kuentz, Martin

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Kuentz
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Martin
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Kuentz, Martin

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2018 - 201912020 - 20221
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Autor:in: Holm, Rene × Autor:in: Koehl, Niklas × Autor:in: Kuentz, Martin × Item-Typ: Publikation × Dateien dazu vorhanden?: Nein ×

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  • Vorschaubild nicht verfügbar
    Publikation
    Lipophilic salts and lipid-based formulations for bridging the food effect gap of venetoclax
    (Elsevier, 01/2022) Koehl, Niklas; Henze, Laura; Holm, Rene; Kuentz, Martin; Keating, John; De Vijlder, Thomas; Marx, Andreas; Griffin, Brendan [in: Journal of Pharmaceutical Sciences]
    Lipid based formulations (LBF) have shown to overcome food dependent bioavailability for some poorly water-soluble drugs. However, the utility of LBFs can be limited by low dose loading due to a low drug solubility in LBF vehicles. This study investigated the solubility and drug loading increases in LBFs using lipophilic counterions to form lipophilic salts of venetoclax. Venetoclax docusate was formed from venetoclax free base and verified by 1H NMR. Formation of stable venetoclax-fatty acid associations with either oleic acid or decanoic acid were attempted, however, the molecular associations were less consistent based on 1H NMR. Venetoclax docusate displayed a up to 6.2-fold higher solubility in self-emulsifying drug delivery systems (SEDDS) when compared to the venetoclax free base solubility resulting in a higher dose loading. A subsequent bioavailability study in landrace pigs demonstrated a 2.5-fold higher bioavailability for the lipophilic salt containing long chain SEDDS compared to the commercially available solid dispersion Venclyxto® in the fasted state. The bioavailability of all lipophilic salt SEDDS in the fasted state was similar to Venclyxto® in the fed state. This study confirmed that lipophilic drug salts increase the dose loading in LBFs and showed that lipophilic salt-SEDDS combinations may be able to overcome bioavailability limitations of drugs with low inherent dose loading in lipid vehicles. Furthermore, the present study demonstrated the utility of a LBF approach, in combination with lipophilic salts, to overcome food dependent variable oral bioavailability of drugs.
    01A - Beitrag in wissenschaftlicher Zeitschrift
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    Publikation
    Approaches to increase mechanistic understanding and aid in the selection of precipitation inhibitors for supersaturating formulations – a PEARRL review
    (Wiley, 05/2018) Price, Daniel J.; Ditzinger, Felix; Koehl, Niklas; Jankovic, Sandra; Tsakiridou, Georgia; Nair, Anita; Holm, Rene; Kuentz, Martin; Dressman, Jennifer; Saal, Christoph [in: Journal of Pharmacy and Pharmacology]
    Objectives Supersaturating formulations hold great promise for delivery of poorly soluble active pharmaceutical ingredients (APIs). To profit from supersaturating formulations, precipitation is hindered with precipitation inhibitors (PIs), maintaining drug concentrations for as long as possible. This review provides a brief overview of supersaturation and precipitation, focusing on precipitation inhibition. Trial‐and‐error PI selection will be examined alongside established PI screening techniques. Primarily, however, this review will focus on recent advances that utilise advanced analytical techniques to increase mechanistic understanding of PI action and systematic PI selection. Key findings Advances in mechanistic understanding have been made possible by the use of analytical tools such as spectroscopy, microscopy and mathematical and molecular modelling, which have been reviewed herein. Using these techniques, PI selection can be guided by molecular rationale. However, more work is required to see widespread application of such an approach for PI selection. Summary Precipitation inhibitors are becoming increasingly important in enabling formulations. Trial‐and‐error approaches have seen success thus far. However, it is essential to learn more about the mode of action of PIs if the most optimal formulations are to be realised. Robust analytical tools, and the knowledge of where and how they can be applied, will be essential in this endeavour.
    01A - Beitrag in wissenschaftlicher Zeitschrift