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| Naji, M. |
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| Motta, Antonella |
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| Aletan, Dirar |
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| Mohamed, Tarek |
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| Ertürk, Emre |
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| Taccardi, Nicola |
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| Kononenko, Denys |
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| Petrov, R. H. | Madrid |
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| Alshaaer, Mazen | Brussels |
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| Bih, L. |
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| Casati, R. |
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| Muller, Hermance |
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| Kočí, Jan | Prague |
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| Šuljagić, Marija |
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| Kalteremidou, Kalliopi-Artemi | Brussels |
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| Azam, Siraj |
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| Ospanova, Alyiya |
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| Blanpain, Bart |
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| Ali, M. A. |
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| Popa, V. |
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| Rančić, M. |
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| Ollier, Nadège |
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| Azevedo, Nuno Monteiro |
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| Landes, Michael |
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| Rignanese, Gian-Marco |
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Alam, K.
in Cooperation with on an Cooperation-Score of 37%
Topics
Publications (19/19 displayed)
- 2023Effect of drill quality on biological damage in bone drillingcitations
- 2022Simulation of buckling-driven progressive damage in composite wind turbine blade under extreme wind loadscitations
- 2022Mechanistic modeling of drug products applied to the skin: A workshop summary report.citations
- 2022Mechanistic Modeling of In Vitro Skin Permeation and Extrapolation to In Vivo for Topically Applied Metronidazole Drug Products Using a Physiologically Based Pharmacokinetic Model.citations
- 2018Influence of Tool Material on Forces, Temperature and Surface Quality of Ti-15333 Alloy in CT and UATcitations
- 2018EXPERIMENTAL STUDY on the EFFECT of DRILL QUALITY on BONE TEMPERATURE in DRILLINGcitations
- 20143D finite-element modelling of drilling cortical bone: Temperature analysis
- 2014Comparative study of conventional and ultrasonically-assisted bone drillingcitations
- 2014Analysis of temperature in conventional and ultrasonically-assisted drilling of cortical bone with infrared thermographycitations
- 2013Analysis of forces in conventional and ultrasonically assisted plane cutting of cortical bonecitations
- 2012On-line analysis of cracking in cortical bone under wedge penetrationcitations
- 2011Experimental investigations of forces and torque in conventional and ultrasonically-assisted drilling of cortical bonecitations
- 2011Experimental investigation of the mechanics of conventional and ultrasonically-assisted drilling of cortical bonecitations
- 2011Analysis of anisotropic viscoelastoplastic properties of cortical bone tissuescitations
- 2010Thermal analysis of orthogonal cutting of cortical bone using finite element simulationscitations
- 2009Measurements of Surface Roughness in Conventional and Ultrasonically Assisted Bone Drillingcitations
- 2009Temperature calculations in orthogonal cutting of cortical bone using finite element analysiscitations
- 2009Finite element analysis of forces of plane cutting of cortical bonecitations
- 2009Stresses in ultrasonically assisted bone cuttingcitations
Places of action
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article
Mechanistic Modeling of In Vitro Skin Permeation and Extrapolation to In Vivo for Topically Applied Metronidazole Drug Products Using a Physiologically Based Pharmacokinetic Model.
Abstract
Physiologically based pharmacokinetic (PBPK) modeling has increasingly been employed in dermal drug development and regulatory assessment, providing a framework to integrate relevant information including drug and drug product attributes, skin physiology parameters, and population variability. The current study aimed to develop a stepwise modeling workflow with knowledge gained from modeling in vitro skin permeation testing (IVPT) to describe in vivo exposure of metronidazole locally in the stratum corneum following topical application of complex semisolid drug products. The initial PBPK model of metronidazole in vitro skin permeation was developed using infinite and finite dose aqueous metronidazole solution. Parameters such as stratum corneum lipid-water partition coefficient (K<sub>sclip/water</sub>) and stratum corneum lipid diffusion coefficient (<i>D</i><sub>sclip</sub>) of metronidazole were optimized using <i>IVPT</i> data from simple aqueous solutions (infinite) and MetroGel (10 mg/cm<sup>2</sup> dose application), respectively. The optimized model, when parameterized with physical and structural characteristics of the drug products, was able to accurately predict the mean cumulative amount permeated (cm<sup>2</sup>/h) and flux (μg/cm<sup>2</sup>/h) profiles of metronidazole following application of different doses of MetroGel and MetroCream. Thus, the model was able to capture the impact of differences in drug product microstructure and metamorphosis of the dosage form on in vitro metronidazole permeation. The PBPK model informed by IVPT study data was able to predict the metronidazole amount in the stratum corneum as reported in clinical studies. In summary, the proposed model provides an enhanced understanding of the potential impact of drug product attributes in influencing in vitro skin permeation of metronidazole. Key kinetic parameters derived from modeling the metronidazole IVPT data improved the predictions of the developed PBPK model of in vivo local metronidazole concentrations in the stratum corneum. Overall, this work improves our confidence in the proposed workflow that accounts for drug product attributes and utilizes IVPT data toward improving predictions from advanced modeling and simulation tools.