The Experts below are selected from a list of 17163 Experts worldwide ranked by ideXlab platform
Lisa M Kaminskas - One of the best experts on this subject based on the ideXlab platform.
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reducing dendrimer generation and peg chain length increases Drug Release and promotes anticancer activity of pegylated polylysine dendrimers conjugated with doxorubicin via a cathepsin cleavable peptide linker
Molecular Pharmaceutics, 2018Co-Authors: Dharmini C Mehta, Nathania Leong, Victoria M Mcleod, Brian D Kelly, Rashmi Pathak, David J Owen, Christopher J H Porter, Lisa M KaminskasAbstract:PEGylation typically improves the systemic exposure and tumor biodistribution of polymeric Drug delivery systems, but may also restrict enzyme access to peptide-based Drug linkers. The impact of dendrimer generation (G4 vs G5) and PEG length (570 vs 1100 Da) on the pharmacoKinetics, tumor biodistribution, Drug Release Kinetics, and anticancer activity of a series of PEGylated polylysine dendrimers conjugated with doxorubicin via a cathepsin-B cleavable valine-citrulline linker was therefore investigated in rodents. Although the smallest G4 PEG570 dendrimer showed the most efficient cathepsin-mediated doxorubicin Release, systemic exposure and tumor uptake were limited. The largest G5 PEG1100 dendrimer showed good tumor uptake and retention but restricted Drug liberation and therefore limited anticancer activity. Superior anticancer activity was achieved using an intermediate sized dendrimer that showed better Drug Release Kinetics, systemic exposure, tumor uptake, and retention. The data suggest that bala...
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Reducing Dendrimer Generation and PEG Chain Length Increases Drug Release and Promotes Anticancer Activity of PEGylated Polylysine Dendrimers Conjugated with Doxorubicin via a Cathepsin-Cleavable Peptide Linker
2018Co-Authors: Dharmini Mehta, Nathania Leong, Victoria M Mcleod, Brian D Kelly, Rashmi Pathak, David J Owen, Christopher J H Porter, Lisa M KaminskasAbstract:PEGylation typically improves the systemic exposure and tumor biodistribution of polymeric Drug delivery systems, but may also restrict enzyme access to peptide-based Drug linkers. The impact of dendrimer generation (G4 vs G5) and PEG length (570 vs 1100 Da) on the pharmacoKinetics, tumor biodistribution, Drug Release Kinetics, and anticancer activity of a series of PEGylated polylysine dendrimers conjugated with doxorubicin via a cathepsin-B cleavable valine-citrulline linker was therefore investigated in rodents. Although the smallest G4 PEG570 dendrimer showed the most efficient cathepsin-mediated doxorubicin Release, systemic exposure and tumor uptake were limited. The largest G5 PEG1100 dendrimer showed good tumor uptake and retention but restricted Drug liberation and therefore limited anticancer activity. Superior anticancer activity was achieved using an intermediate sized dendrimer that showed better Drug Release Kinetics, systemic exposure, tumor uptake, and retention. The data suggest that balancing PEG molecular weight and dendrimer size is critical when designing chemotherapeutic dendrimers
Nicholas A Peppas - One of the best experts on this subject based on the ideXlab platform.
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Drug volume fraction profile in the gel phase and Drug Release Kinetics in hydroxypropylmethyl cellulose matrices containing a soluble Drug
European Journal of Pharmaceutical Sciences, 1999Co-Authors: Paolo Colombo, Ruggero Bettini, P L Catellani, Patrizia Santi, Nicholas A PeppasAbstract:In the present work, the Drug volume fraction profiles of a colored and very soluble Drug, buflomedil pyridoxal phosphate, in the gel layer of initially glassy hydroxypropylmethyl cellulose matrices were studied, using image analysis of pictures of the matrices during swelling and Release. The goal was to correlate the Drug Release Kinetics with the dynamic behavior of the Drug gradient in the gel layer. An inert (nonswellable) matrix, manufactured by substituting hydroxypropylmethyl cellulose with an inert polymer and containing the same amount of buflomedil pyridoxal phosphate, was prepared as well. The Drug color gradient in the partially extracted region and the flux of this matrix were compared to the swellable matrix. The Drug gradient in the dissolved Drug gel layer of swellable matrices was observed. It was demonstrated that Drug Release Kinetics does not only depend on Drug diffusion and matrix erosion, but also on Drug dissolution in the gel and on polymer relaxation.
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a new model describing the swelling and Drug Release Kinetics from hydroxypropyl methylcellulose tablets
Journal of Pharmaceutical Sciences, 1999Co-Authors: J Siepmann, Kairali Podual, M Sriwongjanya, Nicholas A Peppas, Roland BodmeierAbstract:A novel mathematical model for the water transport into and Drug Release from hydroxypropyl methylcellulose (HPMC) tablets is presented. Fick's second law of diffusion is used to describe the mass transfer processes in the three-component system Drug/polymer/ water. Numerical solutions of the respective set of partial differential equations are provided, considering axial and radial diffusion within cylindrical tablets. It is shown that the diffusion coefficients strongly depend on the water concentration (parameters quantifying this dependence have been determined). Swelling of the device is considered using moving boundary conditions, whereas dissolution processes are neglected. Experiments proved the applicability of the theory. The practical benefit of the new model is to calculate the required shape and dimensions of HPMC tablets to achieve a desired Release profile.
F Siepmann - One of the best experts on this subject based on the ideXlab platform.
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how to adjust dexamethasone mobility in silicone matrices a quantitative treatment
European Journal of Pharmaceutics and Biopharmaceutics, 2016Co-Authors: F Siepmann, Juergen Siepmann, M Gehrke, J Sircoglou, C VincentAbstract:Abstract Silicone-based Drug delivery systems offer a great potential to improve the therapeutic efficacy and safety of a large variety of medical treatments, e.g. allowing for local long-term delivery of active agents to the inner ear. Different formulation parameters can be varied to adjust desired Drug Release Kinetics. However, often only qualitative information is available on their effects, and product optimization is cumbersome. The aim of this study was to provide a quantitative analysis, allowing also for theoretical predictions of the impact of the device design on system performance. Dexamethasone was incorporated into thin films based on different types of silicones (e.g. varying in the type of side chains and contents of amorphous silica), optionally containing different types and amounts of poly(ethylene glycol) (PEG) (5% or 10%). Furthermore, the initial Drug content was altered (from 10% to 50%). In most cases, an analytical solution of Fick’s second law could be used to describe the resulting Drug Release Kinetics from the films and to determine the respective “apparent” diffusion coefficient of the Drug (which varied from 2 × 10 −14 to 2 × 10 −12 cm 2 /s, depending on the system’s composition). Thus, the impact of the investigated formulation parameters on Drug mobility in the polymeric matrices could be quantitatively described. Importantly, the knowledge of the “apparent” Drug diffusivity can be used to theoretically predict the resulting Release Kinetics from dosage forms of arbitrary size and shape. For instance, dexamethasone Release was theoretically predicted from cylindrical extrudates based on a selection of different silicone types. Interestingly, these predictions could be confirmed by independent experiments. Hence, this type of quantitative analysis can replace time-consuming and cost-intensive series of trial-and-error experiments during product optimization. This is particularly helpful, if long-term Drug Release (e.g., during several weeks, months or years) is targeted.
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ethanol resistant ethylcellulose guar gum coatings importance of formulation parameters
European Journal of Pharmaceutics and Biopharmaceutics, 2013Co-Authors: Y Rosiaux, C Velghe, S Muschert, R Chokshi, Bruno Leclercq, F SiepmannAbstract:Abstract Recently, ethylcellulose/guar gum blends have been reported to provide ethanol-resistant Drug Release Kinetics from coated dosage forms. This is because the ethanol insoluble guar gum effectively avoids undesired ethylcellulose dissolution in ethanol-rich bulk fluids. However, so far the importance of crucial formulation parameters, including the minimum amount of guar gum to be incorporated and the minimum required guar gum viscosity, remains unclear. The aim of this study was to identify the most important film coating properties, determining whether or not the resulting Drug Release Kinetics is ethanol-resistant. Theophylline matrix cores were coated in a fluid bed with blends of the aqueous ethylcellulose dispersion “Aquacoat® ECD 30” and guar gum. The polymer blend ratio, guar gum viscosity, and degree of dilution of the final coating dispersion were varied. Importantly, it was found that more than 5% guar gum (referred to the total polymer content) must be incorporated in the film coating and that the apparent viscosity of a 1% aqueous guar gum solution must be greater than 150 cP to provide ethanol-resistance. In contrast, the investigated degree of coating dispersion dilution was not found to be decisive for the ethanol sensitivity. Furthermore, all investigated formulations were long term stable, even upon open storage under stress conditions for 6 months.
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controlled Drug Release from gelucire based matrix pellets experiment and theory
International Journal of Pharmaceutics, 2006Co-Authors: F Siepmann, S Muschert, M P Flament, P Leterme, A Gayot, Juergen SiepmannAbstract:The aim of this work was to elucidate the underlying Drug Release mechanisms from lipidic matrix pellets, using theophylline and Gelucire 50/02 as model Drug and carrier material, respectively. Pellets were prepared by two different techniques: melt-solidification and extrusion-spheronization. The effects of different formulations and processing parameters on the resulting Drug Release Kinetics in 0.1N HCl and phosphate buffer pH 7.4 were studied and the obtained results analyzed using adequate mathematical models in order to get further insight into the underlying mass transport mechanisms. The type of preparation technique was found to strongly affect the underlying Drug Release mechanisms. Drug Release from pellets prepared by the melt-solidification method was primarily controlled by pure diffusion, whereas Drug Release from pellets prepared by the extrusion-spheronization method was purely diffusion-controlled only at early time points. After approximately 2 h, the pellets started to disintegrate, resulting in decreased diffusion pathway lengths and, thus, increased Drug Release rates. Furthermore, the curing conditions significantly affected the theophylline Release Kinetics, whereas varying the initial Drug loading from 20 to 50% (w/w) resulted only in a slight increase in the relative Drug Release rate. Interestingly, the effects of the size of pellets prepared by the melt-solidification method on the resulting Drug Release Kinetics could be quantitatively predicted using an analytical solution of Fick's second law of diffusion. These predictions could be verified by independent experiments.
Paolo Colombo - One of the best experts on this subject based on the ideXlab platform.
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Drug Release Kinetics and Front Movement in Matrix Tablets Containing Diltiazem or Metoprolol/λ-Carrageenan Complexes
Hindawi Limited, 2014Co-Authors: Ruggero Bettini, Paolo Colombo, Maria Cristina Bonferoni, Laura Zanelotti, Carla CaramellaAbstract:In this work we investigated the moving boundaries and the associated Drug Release Kinetics in matrix tablets prepared with two complexes between λ-carrageenan and two soluble model Drugs, namely, diltiazem HCl and metoprolol tartrate aiming at clarifying the role played by Drug/polymer interaction on the water uptake, swelling, Drug dissolution, and Drug Release performance of the matrix. The two studied complexes Released the Drug with different mechanism indicating two different Drug/polymer interaction strengths. The comparison between the Drug Release behaviour of the complexes and the relevant physical mixtures indicates that diltiazem gave rise to a less soluble and more stable complex with carrageenan than metoprolol. The less stable metoprolol complex afforded an erodible matrix, whereas the stronger interaction between diltiazem and carrageenan resulted in a poorly soluble, slowly dissolving matrix. It was concluded that the different stability of the studied complexes affords two distinct Drug delivery systems: in the case of MTP, the dissociation of the complex, as a consequence of the interaction with water, affords a classical soluble matrix type delivery system; in the case of DTZ, the dissolving/diffusing species is the complex itself because of the very strong interaction between the Drug and the polymer
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Drug volume fraction profile in the gel phase and Drug Release Kinetics in hydroxypropylmethyl cellulose matrices containing a soluble Drug
European Journal of Pharmaceutical Sciences, 1999Co-Authors: Paolo Colombo, Ruggero Bettini, P L Catellani, Patrizia Santi, Nicholas A PeppasAbstract:In the present work, the Drug volume fraction profiles of a colored and very soluble Drug, buflomedil pyridoxal phosphate, in the gel layer of initially glassy hydroxypropylmethyl cellulose matrices were studied, using image analysis of pictures of the matrices during swelling and Release. The goal was to correlate the Drug Release Kinetics with the dynamic behavior of the Drug gradient in the gel layer. An inert (nonswellable) matrix, manufactured by substituting hydroxypropylmethyl cellulose with an inert polymer and containing the same amount of buflomedil pyridoxal phosphate, was prepared as well. The Drug color gradient in the partially extracted region and the flux of this matrix were compared to the swellable matrix. The Drug gradient in the dissolved Drug gel layer of swellable matrices was observed. It was demonstrated that Drug Release Kinetics does not only depend on Drug diffusion and matrix erosion, but also on Drug dissolution in the gel and on polymer relaxation.
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Drug volume fraction profile in the gel phase and Drug Release Kinetics in hydroxypropylmethyl cellulose matrices containing a soluble Drug
1999Co-Authors: Paolo Colombo, Ruggero Bettini, P L Catellani, Patrizia Santi, Nikolaos A PeppasAbstract:In the present work, the Drug volume fraction profiles of a colored and very soluble Drug, buflomedil pyridoxal phosphate, in the gel layer of initially glassy hydroxypropylmethyl cellulose matrices were studied, using image analysis of pictures of the matrices during swelling and Release. The goal was to correlate the Drug Release Kinetics with the dynamic behavior of the Drug gradient in the gel layer. An inert (nonswellable) matrix, manufactured by substituting hydroxypropylmethyl cellulose with an inert polymer and containing the ..
Weiyuan John Kao - One of the best experts on this subject based on the ideXlab platform.
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Drug Release Kinetics and transport mechanisms of non degradable and degradable polymeric delivery systems
Expert Opinion on Drug Delivery, 2010Co-Authors: Weiyuan John KaoAbstract:Importance of the field: The advancement in material design and engineering has led to the rapid development of new materials with increasing complexity and functions. Both non-degradable and degradable polymers have found wide applications in the controlled delivery field. Studies on Drug Release Kinetics provide important information into the function of material systems. To elucidate the detailed transport mechanism and the structure-function relationship of a material system, it is critical to bridge the gap between the macroscopic data and the transport behavior at the molecular level.Areas covered in this review: The structure and function information of selected non-degradable and degradable polymers have been collected and summarized from literature published after the 1990s. The Release Kinetics of selected Drug compounds from various material systems is discussed in case studies. Recent progress in the mathematical models based on different transport mechanisms is highlighted.What the reader wil...
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Drug Release Kinetics and transport mechanisms from semi interpenetrating networks of gelatin and poly ethylene glycol diacrylate
Pharmaceutical Research, 2009Co-Authors: Weiyuan John KaoAbstract:Purpose To elucidate the key parameters affecting solute transport from semi-interpenetrating networks (sIPNs) comprised of poly(ethylene glycol) diacrylate (PEGdA) and gelatin that are partially crosslinked, water-swellable and biodegradable. Effects of material compositions, solute size, solubility, and loading density have been investigated.
