The Experts below are selected from a list of 2127 Experts worldwide ranked by ideXlab platform
Johannes Khinast - One of the best experts on this subject based on the ideXlab platform.
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Validating a Numerical Simulation of the ConsiGma(R) Coater.
AAPS PharmSciTech, 2020Co-Authors: P. Boehling, Frederik Detobel, James Holman, Laura Wareham, Matthew Metzger, Dalibor Jacevic, Johannes KhinastAbstract:Continuous manufacturing is increasingly used in the pharmaceutical industry, as it promises to deliver better product quality while simultaneously increasing production flexibility. GEA developed a semi-continuous Tablet coater which can be integrated into a continuous Tableting line, accelerating the switch from traditional batch production to the continuous mode of operation. The latter offers certain advantages over batch production, e.g., operational flexibility, increased process/product quality, and decreased cost. However, process understanding is the key element for process control. In this regard, computational tools can improve the fundamental understanding and process performance, especially those related to new processes, such as continuous Tablet Coating where process mechanics remain unclear. The discrete element method (DEM) and computational fluid dynamics (CFD) are two methods that allow transition from empirical process design to a mechanistic understanding of the individual process units. The developed coupling model allows to track the heat, mass, and momentum exchange between the Tablet and fluid phase. The goal of this work was to develop and validate a high-fidelity CFD-DEM simulation model of the Tablet Coating process in the GEA ConsiGma® coater. After the model development, simulation results for the Tablet movement, Coating quality, and heat and mass transfer during the Coating process were validated and compared to the experimental outcomes. The experimental and simulation results agreed well on all accounts measured, indicating that the model can be used in further studies to investigate the operating space of the continuous Tablet Coating process.
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industrial scale simulations of Tablet Coating using gpu based dem a validation study
Chemical Engineering Science, 2019Co-Authors: Hermann Kureck, P. Boehling, Nicolin Govender, Eva Siegmann, Charles Radeke, Johannes KhinastAbstract:Abstract The Coating of Tablets to prevent product degradation or control dissolution is a typical process in its production. Coating uniformity is critical for the quality of final product and batch acceptance. Therefore, the Coating process needs to be optimized in order to achieve the desired uniformity and reduce manufacturing costs. Thus, understanding how process parameters such as spray properties, equipment geometry and Tablet shape influence the Coating process is critical for process optimization and approval by regulatory bodies. However this is a non-trivial task as obtaining information about the detailed processes in a Tablet coater via experimental means is limited. Thus, computational modeling is the most feasible option to obtain information about the physical processes affecting the performance of Tablet coaters. The most widely used computational method for such numerical modelling is the Discrete Element Method (DEM) where individual particles (Tablets) are simulated. However, the computational cost of representing the typical shape of Tablets is high for industrially relevant simulations. Thus Tablet shape is typically approximated by simpler shapes such as spheres or multi spheres. Even with such simplifications, typical simulations take months to complete making it unfeasible for process optimization and design. In the last decade, the Graphical Processor Unit (GPU) has enabled large-scale simulations of tens of millions of spheres and millions of shaped particles using the XPS code. In this paper, we present an algorithm for modeling accurate bi-convex Tablets that is tailored to the GPU. We firstly validate the algorithm and implementation against a number of experiments. Finally we perform a simulation of 20 million Tablets in a drum coater to illustrate the usefulness of GPU computing for industrial Coating applications. We found that the proposed method yields a good match against the lab scale experiments. For the industrial simulation the proposed method gave a more accurate result compared to the multi sphere approach while being significantly faster.
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Comparison of video analysis and simulations of a drum Coating process.
European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences, 2017Co-Authors: P. Boehling, Adrian Funke, Peter Kleinebudde, Gregor Toschkoff, H. Rehbaum, Sarah Just, R. Dreu, Johannes KhinastAbstract:Tablet Coating is a common unit operation in the pharmaceutical industry. To improve currently established processes, it is important to understand the influence of the process parameters on the Coating quality. One of the critical parameters is the Tablet velocity. In this work, numerical results are compared to results obtained experimentally. Tablet movement in the drums was simulated using the Discrete Element Method (DEM). The simulation parameters were adapted to fit the simulation to the experimental data. A comparison of the experimental and simulation results showed that the simulation correctly represents the real Tablet velocity. A change in the velocity over time and its dependence on the rotation rates and the baffle position in the simulation were similar to the experimental results. In summary, simulations can improve the understanding of Tablet Coating processes and will thus provide insights into the underlying process mechanics, which cannot be obtained via ordinary experiments.
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Simulation of a Tablet Coating process at different scales using DEM.
European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences, 2016Co-Authors: P. Boehling, Adrian Funke, Peter Kleinebudde, Klaus Knop, Gregor Toschkoff, H. Rehbaum, Sarah Just, P. Rajniak, Johannes KhinastAbstract:Spray Coating of Tablets is an important unit operation in the pharmaceutical industry and is mainly used for modified release, enteric protection, better appearance and brand recognition. It can also be used to apply an additional active pharmaceutical ingredient to the Tablet core. Scale-up of such a process is an important step in commercialization. However, scale-up is not trivial and frequently, at manufacturing scales the required Coating quality cannot be reached. Thus, we propose a method where laboratory experiments are carried out, yet scale-up is done via computational methods, i.e., by extrapolating results to larger scales. In the recent years, the Discrete Element Method (DEM) has widely been used to simulate Tablet behavior in a laboratory scale drum coater. Due the increasing computational power and more sophisticated DEM algorithms, it has become possible to simulate millions of particles on regular PCs and model industrial scale Tablet Coating devices. In this work, simulations were performed on the laboratory, pilot and industrial scales and DEM was used to study how different scale-up rules influence the bed behavior on larger scales. The material parameters of the Tablets were measured in the laboratory and a glued sphere approach was applied to model the Tablet shape. The results include a vast amount of qualitative and quantitative data at the different scales. In conclusion, the evolution of the inter-Tablet Coating variation for the different scales and process parameters is presented. The results suggest that keeping the Froude number constant during the scale up process leads to faster processes as the cycle time is shorter and the spray residence time is more uniform when compared to keeping the circumferential velocity constant.
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Analysis of large-scale Tablet Coating: Modeling, simulation and experiments.
European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences, 2015Co-Authors: P. Boehling, Adrian Funke, Peter Kleinebudde, Klaus Knop, Gregor Toschkoff, S. Just, H. Rehbaum, Johannes KhinastAbstract:This work concerns a Tablet Coating process in an industrial-scale drum coater. We set up a full-scale Design of Simulation Experiment (DoSE) using the Discrete Element Method (DEM) to investigate the influence of various process parameters (the spray rate, the number of nozzles, the rotation rate and the drum load) on the coefficient of inter-Tablet Coating variation (cv,inter). The coater was filled with up to 290kg of material, which is equivalent to 1,028,369 Tablets. To mimic the Tablet shape, the glued sphere approach was followed, and each modeled Tablet consisted of eight spheres. We simulated the process via the eXtended Particle System (XPS), proving that it is possible to accurately simulate the Tablet Coating process on the industrial scale. The process time required to reach a uniform Tablet Coating was extrapolated based on the simulated data and was in good agreement with experimental results. The results are provided at various levels of details, from thorough investigation of the influence that the process parameters have on the cv,inter and the amount of Tablets that visit the spray zone during the simulated 90s to the velocity in the spray zone and the spray and bed cycle time. It was found that increasing the number of nozzles and decreasing the spray rate had the highest influence on the cv,inter. Although increasing the drum load and the rotation rate increased the Tablet velocity, it did not have a relevant influence on the cv,inter and the process time.
Jean-manuel Péan - One of the best experts on this subject based on the ideXlab platform.
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comparative static curing versus dynamic curing on Tablet Coating structures
International Journal of Pharmaceutics, 2013Co-Authors: Claire Gendre, Olivier Lecoq, Mathieu Boiret, Arafat Tfayli, Pierre Chaminade, Michel Baron, Muriel Genty, Barbara Fayard, Jean-manuel PéanAbstract:Abstract Curing is generally required to stabilize film Coating from aqueous polymer dispersion. This post-Coating drying step is traditionally carried out in static conditions, requiring the transfer of solid dosage forms to an oven. But, curing operation performed directly inside the Coating equipment stands for an attractive industrial application. Recently, the use of various advanced physico-chemical characterization techniques i.e., X-ray micro-computed tomography, vibrational spectroscopies (near infrared and Raman) and X-ray microdiffraction, allowed new insights into the film-Coating structures of dynamically cured Tablets. Dynamic curing end-point was efficiently determined after 4 h. The aim of the present work was to elucidate the influence of curing conditions on film-Coating structures. Results demonstrated that 24 h of static curing and 4 h of dynamic curing, both performed at 60 °C and ambient relative humidity, led to similar Coating layers in terms of drug release properties, porosity, water content, structural rearrangement of polymer chains and crystalline distribution. Furthermore, X-ray microdiffraction measurements pointed out different crystalline Coating compositions depending on sample storage time. An aging mechanism might have occur during storage, resulting in the crystallization and the upward migration of cetyl alcohol, coupled to the downward migration of crystalline sodium lauryl sulfate within the Coating layer. Interestingly, this new study clearly provided further knowledge into film-Coating structures after a curing step and confirmed that curing operation could be performed in dynamic conditions.
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Comparative static curing versus dynamic curing on Tablet Coating structures
International Journal of Pharmaceutics, 2013Co-Authors: Claire Gendre, Olivier Lecoq, Mathieu Boiret, Arafat Tfayli, Pierre Chaminade, Michel Baron, Muriel Genty, Barbara Fayard, Jean-manuel PéanAbstract:Curing is generally required to stabilize film Coating from aqueous polymer dispersion. This post-Coating drying step is traditionally carried out in static conditions, requiring the transfer of solid dosage forms to an oven. But, curing operation performed directly inside the Coating equipment stands for an attractive industrial application. Recently, the use of various advanced physico-chemical characterization techniques i.e., X-ray micro-computed tomography, vibrational spectroscopies (near infrared and Raman) and X-ray microdiffraction, allowed new insights into the film-Coating structures of dynamically cured Tablets. Dynamic curing end-point was efficiently determined after 4 h. The aim of the present work was to elucidate the influence of curing conditions on film-Coating structures. Results demonstrated that 24 h of static curing and 4 h of dynamic curing, both performed at 60 degrees C and ambient relative humidity, led to similar Coating layers in terms of drug release properties, porosity, water content, structural rearrangement of polymer chains and crystalline distribution. Furthermore, X-ray microdiffraction measurements pointed out different crystalline Coating compositions depending on sample storage time. An aging mechanism might have occur during storage, resulting in the crystallization and the upward migration of cetyl alcohol, coupled to the downward migration of crystalline sodium lauryl sulfate within the Coating layer. Interestingly, this new study clearly provided further knowledge into film-Coating structures after a curing step and confirmed that curing operation could be performed in dynamic conditions. (C) 2013 Elsevier B.V. All rights reserved.
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Comparative static curing versus dynamic curing on Tablet Coating structures
International Journal of Pharmaceutics, 2013Co-Authors: Claire Gendre, Olivier Lecoq, Mathieu Boiret, Arafat Tfayli, Pierre Chaminade, Michel Baron, Muriel Genty, Barbara Fayard, Jean-manuel PéanAbstract:Curing is generally required to stabilize film Coating from aqueous polymer dispersion. This post-Coating drying step is traditionally carried out in static conditions, requiring the transfer of solid dosage forms to an oven. But, curing operation performed directly inside the Coating equipment stands for an attractive industrial application. Recently, the use of various advanced physico-chemical characterization techniques i.e., X-ray micro-computed tomography, vibrational spectroscopies (near infrared and Raman) and X-ray microdiffraction, allowed new insights into the film-Coating structures of dynamically cured Tablets. Dynamic curing end-point was efficiently determined after 4 h. The aim of the present work was to elucidate the influence of curing conditions on film-Coating structures. Results demonstrated that 24 h of static curing and 4 h of dynamic curing, both performed at 60 degrees C and ambient relative humidity, led to similar Coating layers in terms of drug release properties, porosity, water content, structural rearrangement of polymer chains and crystalline distribution. Furthermore, X-ray microdiffraction measurements pointed out different crystalline Coating compositions depending on sample storage time. An aging mechanism might have occur during storage, resulting in the crystallization and the upward migration of cetyl alcohol, coupled to the downward migration of crystalline sodium lauryl sulfate within the Coating layer. Interestingly, this new study clearly provided further knowledge into film-Coating structures after a curing step and confirmed that curing operation could be performed in dynamic conditions.
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Comprehensive study of dynamic curing effect on Tablet Coating structure.
European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V, 2012Co-Authors: Claire Gendre, Olivier Lecoq, Mathieu Boiret, Arafat Tfayli, Pierre Chaminade, Michel Baron, Muriel Genty, Julio Cesar Da Silva, Jean-manuel PéanAbstract:The dissolution method is still widely used to determine curing end-points to ensure long-term stability of film Coatings. Nevertheless, the process of curing has not yet been fully investigated. For the first time, joint techniques were used to elucidate the mechanisms of dynamic curing over time from ethylcellulose (Aquacoat)-based coated Tablets. X-ray micro-computed tomography (XμCT), Near Infrared (NIR), and Raman spectroscopies as well as X-ray microdiffraction were employed as non-destructive techniques to perform direct measurements on Tablets. All techniques indicated that after a dynamic curing period of 4h, reproducible drug release can be achieved and no changes in the microstructure of the Coating were any longer detected. XμCT analysis highlighted the reduced internal porosity, while both NIR and Raman measurements showed that spectral information remained unaltered after further curing. X-ray microdiffraction revealed densification of the Coating layer with a decrease in the overall Coating thickness of about 10 μm as a result of curing. In addition, Coating heterogeneity attributed to cetyl alcohol was observed from microscopic images and Raman analysis. This observation was confirmed by X-ray microdiffraction that showed that crystalline cetyl alcohol melted and spread over the Coating surface with curing. Prior to curing, X-ray microdiffraction also revealed the existence of two Coating zones differing in crystalline cetyl alcohol and sodium lauryl sulfate concentrations which could be explained by migration of these constituents within the Coating layer. Therefore, the use of non-destructive techniques allowed new insights into Tablet Coating structures and provided precise determination of the curing end-point compared to traditional dissolution testing. This thorough study may open up new possibilities for process and formulation control.
Peter Kleinebudde - One of the best experts on this subject based on the ideXlab platform.
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Effect of Coating time on inter- and intra-Tablet Coating uniformity.
European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences, 2019Co-Authors: Juliana Radtke, Raphael Wiedey, Peter KleinebuddeAbstract:Film Tablets are a common oral dosage from. For many of the functions film layers can have on pharmaceutical Tablets, a high degree of Coating uniformity is required. In studies on Coating uniformity the coefficient of variation is commonly used as a marker. Previous studies regarding the trend were mostly extrapolations from simulations of short Coating times. Based on these it was stated that the inter Tablet coefficient of variation decreases proportionally to one over the square root of Coating time and hence diverge asymptotically towards zero. Extrapolations of experimental data suggested however a decrease converging to a residual value. Based on these results it can be hypothesized that the coefficient of variation decreases proportionally to one over time towards a residual value. Regarding intra-Tablet Coating homogeneity, no data on time dependency has been published so far. In this study, three long time Coating experiments were performed to test the described hypotheses. The inter-Tablet uniformity was derived gravimetrically, while the intra-Tablet data was derived using micro-computed tomography and confocal chromatic thickness determination. Towards the end of the Coating experiments, a non-zero plateau of inter-Tablet uniformity was reached. Furthermore, the data showed non-random deviations from the hypothesized one-over-square-root-of-time-model. The data for intra-Tablet uniformity showed a non-linear decrease as well, but did not allow falsification of either hypothesis. It was additionally found that the cap-to-band ratio was below one at short Coating times and increased to values above 1 during the process, which implies that existing declarations from literature might be limited to certain process durations.
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Optimization of a semi-batch Tablet Coating process for a continuous manufacturing line by design of experiments
International journal of pharmaceutics, 2018Co-Authors: Shirin Barimani, Rok Šibanc, Peter KleinebuddeAbstract:Abstract The aim of the study was to optimize a Tablet Coating process for a continuous manufacturing line. High throughputs should be achieved while inter-Tablet Coating variability should be as small as possible. Drug-free cores were coated with a colored suspension. All processes were monitored in-line with Raman spectroscopy. A statistical design of experiment was performed to find optimum process parameters. Tablet loading, spray rate and drum rotation speed were studied. Image analysis was performed using a computer scanner. Tablet hue and saturation were evaluated to obtain information about the inter-Tablet color variabilities and the numbers of outliers. Low variabilities could be achieved using low spray rates and high rotation speeds and they were independent from the Tablet batch sizes in the studied factor space. For the prediction of the Coating thickness, univariate analysis was compared to PLS-regression. Calibration models were built based on the three center points of the statistical design of experiment resulting in RMSEC of 1.07% of sprayed suspension with R2 of 0.9989 and Q2 of 0.9987. Model prediction was possible independent from loading, spray rate and drum rotation speed. The experiment with lowest color variability was conducted with a desired throughput rate of 25 kg/h and with a RMSEP of 2.5%.
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Monitoring of Tablet Coating processes with colored Coatings
Talanta, 2017Co-Authors: Shirin Barimani, Peter KleinebuddeAbstract:Abstract Endpoints of Coating processes for colored Tablets were determined using in-line Raman spectroscopy. Coatings were performed with six commercially available formulations of pink, yellow, red, beige, green and blue color. The Coatings were comprising pigments and/or dyes, some causing fluorescence and interfering the Raman signal. Using non-contact optics, a Raman probe was used as process analytical technology (PAT) tool, and acquired spectra were correlated to the sprayed mass of aqueous Coating suspension. Process endpoints were determined using univariate (UV) data analysis and three multivariate analysis methods, namely Projection to Latent Structures (PLS)-regression, Science-Based Calibration (SBC) and Multivariate Curve Resolution (MCR). The methods were compared regarding model performance parameters. The endpoints of all Coating experiments could be predicted until a total Coating time of 50 min corresponding to Coating thicknesses between 21 and 38 µm, depending on the density of the coat formulation. With the exception of SBC, all calibration methods resulted in R2 values higher than 0.9. Additionally, the methods were evaluated regarding their capability for in-line process monitoring. For each color, at least two methods were feasible to do this. Overall, PLS-regression led to best model performance parameters.
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Comparison of video analysis and simulations of a drum Coating process.
European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences, 2017Co-Authors: P. Boehling, Adrian Funke, Peter Kleinebudde, Gregor Toschkoff, H. Rehbaum, Sarah Just, R. Dreu, Johannes KhinastAbstract:Tablet Coating is a common unit operation in the pharmaceutical industry. To improve currently established processes, it is important to understand the influence of the process parameters on the Coating quality. One of the critical parameters is the Tablet velocity. In this work, numerical results are compared to results obtained experimentally. Tablet movement in the drums was simulated using the Discrete Element Method (DEM). The simulation parameters were adapted to fit the simulation to the experimental data. A comparison of the experimental and simulation results showed that the simulation correctly represents the real Tablet velocity. A change in the velocity over time and its dependence on the rotation rates and the baffle position in the simulation were similar to the experimental results. In summary, simulations can improve the understanding of Tablet Coating processes and will thus provide insights into the underlying process mechanics, which cannot be obtained via ordinary experiments.
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Simulation of a Tablet Coating process at different scales using DEM.
European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences, 2016Co-Authors: P. Boehling, Adrian Funke, Peter Kleinebudde, Klaus Knop, Gregor Toschkoff, H. Rehbaum, Sarah Just, P. Rajniak, Johannes KhinastAbstract:Spray Coating of Tablets is an important unit operation in the pharmaceutical industry and is mainly used for modified release, enteric protection, better appearance and brand recognition. It can also be used to apply an additional active pharmaceutical ingredient to the Tablet core. Scale-up of such a process is an important step in commercialization. However, scale-up is not trivial and frequently, at manufacturing scales the required Coating quality cannot be reached. Thus, we propose a method where laboratory experiments are carried out, yet scale-up is done via computational methods, i.e., by extrapolating results to larger scales. In the recent years, the Discrete Element Method (DEM) has widely been used to simulate Tablet behavior in a laboratory scale drum coater. Due the increasing computational power and more sophisticated DEM algorithms, it has become possible to simulate millions of particles on regular PCs and model industrial scale Tablet Coating devices. In this work, simulations were performed on the laboratory, pilot and industrial scales and DEM was used to study how different scale-up rules influence the bed behavior on larger scales. The material parameters of the Tablets were measured in the laboratory and a glued sphere approach was applied to model the Tablet shape. The results include a vast amount of qualitative and quantitative data at the different scales. In conclusion, the evolution of the inter-Tablet Coating variation for the different scales and process parameters is presented. The results suggest that keeping the Froude number constant during the scale up process leads to faster processes as the cycle time is shorter and the spray residence time is more uniform when compared to keeping the circumferential velocity constant.
J. Axel Zeitler - One of the best experts on this subject based on the ideXlab platform.
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Investigating Intra-Tablet Coating Uniformity With Spectral-Domain Optical Coherence Tomography.
Journal of pharmaceutical sciences, 2016Co-Authors: Yue Dong, J. Axel Zeitler, Hungyen Lin, Vahid Abolghasemi, Lu Gan, Yao-chun ShenAbstract:Spectral domain optical coherence tomography (SD-OCT) has recently attracted a lot of interest in the pharmaceutical industry as a fast and non-destructive modality for direct quantification of thin film Coatings that cannot easily be resolved with other techniques. While previous studies with SD-OCT have estimated the intra-Tablet Coating uniformity, the estimates were based on limited number of B-scans. In order to obtain a more accurate estimate, a greater number of B-scans are required that can quickly lead to an overwhelming amount of data. To better manage the data so as to generate a more accurate representation of the intra-Tablet Coating uniformity without compromising on the achievable axial resolution and imaging depth, we comprehensively examine an algebraic reconstruction technique with OCT to significantly reduce the data required. Specifically, a set of coated pharmaceutical Tablets with film Coating thickness in the range of 60-100 μm is investigated. Results obtained from performing the reconstruction reveal that only 30% of the acquired data are actually required leading to a faster convergence time and a generally good agreement with benchmark data against the intra-Tablet Coating uniformity measured with terahertz pulsed imaging technology.
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Comparisons of intra-Tablet Coating variability using DEM simulations, asymptotic limit models, and experiments
Chemical Engineering Science, 2015Co-Authors: Ben Freireich, William R. Ketterhagen, Rahul Kumar, Carl Wassgren, J. Axel ZeitlerAbstract:Abstract Discrete element method (DEM) computer simulations are used to investigate intra-Tablet Coating thickness variability. Two new post-processing algorithms are presented. The first algorithm uses an image-based method to track the exposure to a simulated spray of small area panels on each Tablet׳s surface so that the distribution of spray exposure times over the Tablet׳s surface can be determined directly from DEM data. The second algorithm predicts the asymptotic limit of intra-Tablet Coating uniformity. This second algorithm includes the influence of Tablet orientation and shadowing when considering exposure to the spray, averaged over many Tablets. The DEM simulations produce the first direct evidence that non-spherical Tablets approach asymptotic intra-Tablet Coating variability values. The asymptotic limits are predicted well using the new asymptotic prediction model. In general, Tablet caps have thicker Coatings than Tablet bands. Moreover, Tablets that have a more elongated shape tend to have less Coating on the smaller radius of curvature portions of the bands. Of particular importance in this new asymptotic modeling approach is the inclusion of shadowing effects. When shadowing is not included and only Tablet orientation is considered, the predictions over-predict the asymptotic intra-Tablet Coating variability values and also change the observed rank order of the asymptotic values for different Tablet shapes. The asymptotic intra-Tablet Coating variability values using the new algorithm correlate reasonably well with Tablet sphericity, with increasing sphericity improving Coating uniformity. This paper also presents the first attempt to directly compare experimental and simulated Coating thickness distributions. The asymptotic Coating thickness predictions compare well qualitatively with terahertz thickness measurements made on Tablets from Coating experiments. Unfortunately, only qualitative comparisons could be made due to the limited number of Tablets sampled experimentally and differences in spray zone areas and flux distributions. The Tablets in the experiments, however, displayed similar features as those found in the simulations.
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Evaluation of critical process parameters for intra-Tablet Coating uniformity using terahertz pulsed imaging.
European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V, 2013Co-Authors: Daniela Brock, Adrian Funke, J. Axel Zeitler, Klaus Knop, Peter KleinebuddeAbstract:The purpose of this study was to evaluate the intra-Tablet Coating uniformity and the identification of critical process parameters in an active pan Coating process using terahertz pulsed imaging (TPI). A design of experiments (DoE) was performed with drum load, drum speed, spray rate, run duration and spray pressure as factors. Different measures of intra-Tablet uniformity were investigated: the average thickness on the individual Tablet faces, spatial variation in layer thickness over the Tablet surface, and the coefficient of variation (CV(intra)). Data analysis revealed that the process parameters in the investigated parameter space had hardly any influence on the difference in layer thickness of the Tablet faces and centre band. No increase or decrease in layer thickness--as described in the literature--was found towards the edges of the Tablet face. In overwetted process conditions a higher layer thickness at the centre band edges could be observed. Still, the highest variability in Coating thickness was found along the circumference of the centre band rather than the height. In general, higher CV(intra) of layer thickness were found on the centre bands in comparison with the Tablet faces. The analysis of the DoE model revealed that the run duration had the highest influence on the CV(intra) on the Tablet faces. TPI showed high potential in the assessment of intra-Tablet uniformity and layer thickness distributions over the whole Tablet surface. It was successfully used to identify critical process parameters regarding intra-Tablet Coating uniformity.
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Studying pharmaceutical Tablet Coating process with real-time terahertz in-line sensing
2013 38th International Conference on Infrared Millimeter and Terahertz Waves (IRMMW-THz), 2013Co-Authors: Hungyen Lin, Shun-cong Zhong, Yao-chun Shen, Robert K. May, Lynn F. Gladden, Michael J. Evans, Ian Warr, J. Axel ZeitlerAbstract:Terahertz in-line sensing was successfully demonstrated previously for measuring the Coating thickness of individual pharmaceutical Tablets during a production scale film Coating process. This paper investigates how this technology can be used to evaluate the impact of changes in the process conditions on the inter-Tablet Coating thickness distribution. The process changes that were investigated in this study were the removal of the mixing baffles from the Coating pan, blockage of one of the spray guns and the addition of uncoated Tablet cores to a bed of partially coated Tablets. Using the terahertz sensor the Coating thickness of more than 20 individual Tablets was sampled per minute in situ throughout the Coating process. By analysing the resulting variation in Coating thickness distribution it was possible to resolve the effect of all these process changes on the Coating thickness homogeneity within the batch.
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Quantification of thin-film Coating thickness of pharmaceutical Tablets using wavelet analysis of terahertz pulsed imaging data
34th International Conference on Infrared Millimeter and Terahertz Waves IRMMW-THz 2009, 2009Co-Authors: Shun-cong Zhong, Mike Evans, Yao-chun Shen, Robert K. May, Lynn F. Gladden, J. Axel Zeitler, Chris ByersAbstract:Terahertz pulsed imaging (TPI) is a powerful tool for nondestructive and quantitative characterization of pharmaceutical Tablet Coatings. In this paper, we present various processing methods for determining Coating thickness from the measured terahertz waveform. We demonstrate that a wavelet-based method can be used to characterize the Tablet Coating with a thickness down to 25 microns, which is better than a conventional “peak-finding” method. Experimental results demonstrated that this new method is also applicable to real-time in-situ monitoring and control of pharmaceutical manufacture processes.
Claire Gendre - One of the best experts on this subject based on the ideXlab platform.
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comparative static curing versus dynamic curing on Tablet Coating structures
International Journal of Pharmaceutics, 2013Co-Authors: Claire Gendre, Olivier Lecoq, Mathieu Boiret, Arafat Tfayli, Pierre Chaminade, Michel Baron, Muriel Genty, Barbara Fayard, Jean-manuel PéanAbstract:Abstract Curing is generally required to stabilize film Coating from aqueous polymer dispersion. This post-Coating drying step is traditionally carried out in static conditions, requiring the transfer of solid dosage forms to an oven. But, curing operation performed directly inside the Coating equipment stands for an attractive industrial application. Recently, the use of various advanced physico-chemical characterization techniques i.e., X-ray micro-computed tomography, vibrational spectroscopies (near infrared and Raman) and X-ray microdiffraction, allowed new insights into the film-Coating structures of dynamically cured Tablets. Dynamic curing end-point was efficiently determined after 4 h. The aim of the present work was to elucidate the influence of curing conditions on film-Coating structures. Results demonstrated that 24 h of static curing and 4 h of dynamic curing, both performed at 60 °C and ambient relative humidity, led to similar Coating layers in terms of drug release properties, porosity, water content, structural rearrangement of polymer chains and crystalline distribution. Furthermore, X-ray microdiffraction measurements pointed out different crystalline Coating compositions depending on sample storage time. An aging mechanism might have occur during storage, resulting in the crystallization and the upward migration of cetyl alcohol, coupled to the downward migration of crystalline sodium lauryl sulfate within the Coating layer. Interestingly, this new study clearly provided further knowledge into film-Coating structures after a curing step and confirmed that curing operation could be performed in dynamic conditions.
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Comparative static curing versus dynamic curing on Tablet Coating structures
International Journal of Pharmaceutics, 2013Co-Authors: Claire Gendre, Olivier Lecoq, Mathieu Boiret, Arafat Tfayli, Pierre Chaminade, Michel Baron, Muriel Genty, Barbara Fayard, Jean-manuel PéanAbstract:Curing is generally required to stabilize film Coating from aqueous polymer dispersion. This post-Coating drying step is traditionally carried out in static conditions, requiring the transfer of solid dosage forms to an oven. But, curing operation performed directly inside the Coating equipment stands for an attractive industrial application. Recently, the use of various advanced physico-chemical characterization techniques i.e., X-ray micro-computed tomography, vibrational spectroscopies (near infrared and Raman) and X-ray microdiffraction, allowed new insights into the film-Coating structures of dynamically cured Tablets. Dynamic curing end-point was efficiently determined after 4 h. The aim of the present work was to elucidate the influence of curing conditions on film-Coating structures. Results demonstrated that 24 h of static curing and 4 h of dynamic curing, both performed at 60 degrees C and ambient relative humidity, led to similar Coating layers in terms of drug release properties, porosity, water content, structural rearrangement of polymer chains and crystalline distribution. Furthermore, X-ray microdiffraction measurements pointed out different crystalline Coating compositions depending on sample storage time. An aging mechanism might have occur during storage, resulting in the crystallization and the upward migration of cetyl alcohol, coupled to the downward migration of crystalline sodium lauryl sulfate within the Coating layer. Interestingly, this new study clearly provided further knowledge into film-Coating structures after a curing step and confirmed that curing operation could be performed in dynamic conditions. (C) 2013 Elsevier B.V. All rights reserved.
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Comparative static curing versus dynamic curing on Tablet Coating structures
International Journal of Pharmaceutics, 2013Co-Authors: Claire Gendre, Olivier Lecoq, Mathieu Boiret, Arafat Tfayli, Pierre Chaminade, Michel Baron, Muriel Genty, Barbara Fayard, Jean-manuel PéanAbstract:Curing is generally required to stabilize film Coating from aqueous polymer dispersion. This post-Coating drying step is traditionally carried out in static conditions, requiring the transfer of solid dosage forms to an oven. But, curing operation performed directly inside the Coating equipment stands for an attractive industrial application. Recently, the use of various advanced physico-chemical characterization techniques i.e., X-ray micro-computed tomography, vibrational spectroscopies (near infrared and Raman) and X-ray microdiffraction, allowed new insights into the film-Coating structures of dynamically cured Tablets. Dynamic curing end-point was efficiently determined after 4 h. The aim of the present work was to elucidate the influence of curing conditions on film-Coating structures. Results demonstrated that 24 h of static curing and 4 h of dynamic curing, both performed at 60 degrees C and ambient relative humidity, led to similar Coating layers in terms of drug release properties, porosity, water content, structural rearrangement of polymer chains and crystalline distribution. Furthermore, X-ray microdiffraction measurements pointed out different crystalline Coating compositions depending on sample storage time. An aging mechanism might have occur during storage, resulting in the crystallization and the upward migration of cetyl alcohol, coupled to the downward migration of crystalline sodium lauryl sulfate within the Coating layer. Interestingly, this new study clearly provided further knowledge into film-Coating structures after a curing step and confirmed that curing operation could be performed in dynamic conditions.
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Comprehensive study of dynamic curing effect on Tablet Coating structure.
European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V, 2012Co-Authors: Claire Gendre, Olivier Lecoq, Mathieu Boiret, Arafat Tfayli, Pierre Chaminade, Michel Baron, Muriel Genty, Julio Cesar Da Silva, Jean-manuel PéanAbstract:The dissolution method is still widely used to determine curing end-points to ensure long-term stability of film Coatings. Nevertheless, the process of curing has not yet been fully investigated. For the first time, joint techniques were used to elucidate the mechanisms of dynamic curing over time from ethylcellulose (Aquacoat)-based coated Tablets. X-ray micro-computed tomography (XμCT), Near Infrared (NIR), and Raman spectroscopies as well as X-ray microdiffraction were employed as non-destructive techniques to perform direct measurements on Tablets. All techniques indicated that after a dynamic curing period of 4h, reproducible drug release can be achieved and no changes in the microstructure of the Coating were any longer detected. XμCT analysis highlighted the reduced internal porosity, while both NIR and Raman measurements showed that spectral information remained unaltered after further curing. X-ray microdiffraction revealed densification of the Coating layer with a decrease in the overall Coating thickness of about 10 μm as a result of curing. In addition, Coating heterogeneity attributed to cetyl alcohol was observed from microscopic images and Raman analysis. This observation was confirmed by X-ray microdiffraction that showed that crystalline cetyl alcohol melted and spread over the Coating surface with curing. Prior to curing, X-ray microdiffraction also revealed the existence of two Coating zones differing in crystalline cetyl alcohol and sodium lauryl sulfate concentrations which could be explained by migration of these constituents within the Coating layer. Therefore, the use of non-destructive techniques allowed new insights into Tablet Coating structures and provided precise determination of the curing end-point compared to traditional dissolution testing. This thorough study may open up new possibilities for process and formulation control.
