Kuentz, Martin

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Kuentz
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Martin
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Kuentz, Martin

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2018 - 201932020 - 20232
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Autor:in: Dressman, Jennifer × Hochschule: Hochschule für Life Sciences ×

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Gerade angezeigt 1 - 5 von 5
  • Vorschaubild
    Publikation
    Leveraging the use of in vitro and computational methods to support the development of enabling oral drug products. An InPharma commentary
    (Elsevier, 01.09.2023) Reppas, Christos; Kuentz, Martin; Bauer-Brandl, Annette; Carlert, Sara; Dallmann, André; Dietrich, Shirin; Dressman, Jennifer; Ejskjaer, Lotte; Frechen, Sebastian; Guidetti, Matteo; Holm, René; Holzem, Florentin Lukas; Karlsson, Εva; Kostewicz, Edmund; Panbachi, Shaida; Paulus, Felix; Senniksen, Malte Bøgh; Stillhart, Cordula; Turner, David B.; Vertzoni, Maria; Vrenken, Paul; Zöller, Laurin; Griffin, Brendan T.; O'Dwyer, Patrick J. [in: European Journal of Pharmaceutical Sciences]
    01A - Beitrag in wissenschaftlicher Zeitschrift
  • Vorschaubild nicht verfügbar
    Publikation
    Incorporation of HPMCAS during loading of glibenclamide onto mesoporous silica improves dissolution and inhibits precipitation
    (Elsevier, 01/2020) Price, Daniel J.; Nair, Anita; Becker-Baldus, Johanna; Glaubitz, Clemens; Kuentz, Martin; Dressman, Jennifer; Saal, Christoph [in: European Journal of Pharmaceutical Sciences]
    Mesoporous silica has emerged as an enabling formulation for poorly soluble active pharmaceutical ingredients (APIs). Unlike other formulations, mesoporous silica typically does not inhibit precipitation of supersaturated API therefore, a suitable precipitation inhibitor (PI) should be added to increase absorption from the gastrointestinal (GI) tract. However, there is limited research about optimal processes for combining PIs with silica formulations. Typically, the PI is added by simply blending the API-loaded silica mechanically with the selected PI. This has the drawback of an additional blending step and may also not be optimal with regard to release of drug and PI. By contrast, loading PI simultaneously with the API onto mesoporous silica, i.e. co-incorporation, is attractive from both a performance and practical perspective. The aim of this study was to demonstrate the utility of a co-incorporation approach for combining PIs with silica formulations, and to develop a mechanistic rationale for improvement of the performance of silica formulations using the co-incorporation approach. The results indicate that co-incorporating HPMCAS with glibenclamide onto silica significantly improved the extent and duration of drug supersaturation in single-medium and transfer dissolution experiments. Extensive spectroscopic characterization of the formulation revealed that the improved performance was related to the formation of drug-polymer interactions already in the solid state; the immobilization of API-loaded silica on HPMCAS plates, which prevents premature release and precipitation of API; and drug-polymer proximity on disintegration of the formulation, allowing for rapid onset of precipitation inhibition. The data suggests that co-incorporating the PI with the API is appealing for silica formulations from both a practical and formulation performance perspective.
    01A - Beitrag in wissenschaftlicher Zeitschrift
  • Vorschaubild
    Publikation
    Opportunities for Successful Stabilization of Poor Glass-Forming Drugs: A Stability-Based Comparison of Mesoporous Silica Versus Hot Melt Extrusion Technologies
    (Elsevier, 04.11.2019) Ditzinger, Felix; Price, Daniel J.; Nair, Anita; Becker-Baldus, Johanna; Glaubitz, Clemens; Dressman, Jennifer; Saal, Christoph; Kuentz, Martin [in: Pharmaceutics]
    Amorphous formulation technologies to improve oral absorption of poorly soluble active pharmaceutical ingredients (APIs) have become increasingly prevalent. Currently, polymer-based amorphous formulations manufactured by spray drying, hot melt extrusion (HME), or co-precipitation are most common. However, these technologies have challenges in terms of the successful stabilization of poor glass former compounds in the amorphous form. An alternative approach is mesoporous silica, which stabilizes APIs in non-crystalline form via molecular adsorption inside nano-scale pores. In line with these considerations, two poor glass formers, haloperidol and carbamazepine, were formulated as polymer-based solid dispersion via HME and with mesoporous silica, and their stability was compared under accelerated conditions. Changes were monitored over three months with respect to solid-state form and dissolution. The results were supported by solid-state nuclear magnetic resonance spectroscopy (SS-NMR) and scanning electron microscopy (SEM). It was demonstrated that mesoporous silica was more successful than HME in the stabilization of the selected poor glass formers. While both drugs remained non-crystalline during the study using mesoporous silica, polymer-based HME formulations showed recrystallization after one week. Thus, mesoporous silica represents an attractive technology to extend the formulation toolbox to poorly soluble poor glass formers.
    01A - Beitrag in wissenschaftlicher Zeitschrift
  • Vorschaubild nicht verfügbar
    Publikation
    In vitro methods to assess drug precipitation in the fasted small intestine – a PEARRL review
    (Wiley, 06/2018) O'Dwyer, Patrick J.; Litou, Chara; Box, Karl, J.; Dressman, Jennifer; Kostewicz, Edmund, S.; Kuentz, Martin; Reppas, Christos [in: Journal of Pharmacy and Pharmacology]
    Objectives Drug precipitation in vivo poses a significant challenge for the pharmaceutical industry. During the drug development process, the impact of drug supersaturation or precipitation on the in vivo behaviour of drug products is evaluated with in vitro techniques. This review focuses on the small and full scale in vitro methods to assess drug precipitation in the fasted small intestine. Key findings Many methods have been developed in an attempt to evaluate drug precipitation in the fasted state, with varying degrees of complexity and scale. In early stages of drug development, when drug quantities are typically limited, small‐scale tests facilitate an early evaluation of the potential precipitation risk in vivo and allow rapid screening of prototype formulations. At later stages of formulation development, full‐scale methods are necessary to predict the behaviour of formulations at clinically relevant doses. Multicompartment models allow the evaluation of drug precipitation after transfer from stomach to the upper small intestine. Optimisation of available biopharmaceutics tools for evaluating precipitation in the fasted small intestine is crucial for accelerating the development of novel breakthrough medicines and reducing the development costs. Summary Despite the progress from compendial quality control dissolution methods, further work is required to validate the usefulness of proposed setups and to increase their biorelevance, particularly in simulating the absorption of drug along the intestinal lumen. Coupling results from in vitro testing with physiologically based pharmacokinetic modelling holds significant promise and requires further evaluation.
    01A - Beitrag in wissenschaftlicher Zeitschrift
  • Vorschaubild nicht verfügbar
    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