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Nofrerias Roig Isaac - One of the best experts on this subject based on the ideXlab platform.
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Aplicació de la simulació de compressió a l’estudi del comportament i optimització de comprimits elaborats per compressió directa utilitzant el sistema expert SeDeM
'Edicions de la Universitat de Barcelona', 2019Co-Authors: Nofrerias Roig IsaacAbstract:[cat] El comprimit és la forma farmacèutica més freqüent al mercat. El procés tecnològic d’elaboració de comprimits d’elecció és la compressió directa perquè permet un estalvi en el nombre d’etapes. Tanmateix, aquest procés requereix que les pólvores presentin unes característiques adequades per la compressió per se. La necessitat de dissenyar ràpidament una fórmula farmacèutica que compleixi els estàndards de compressió i l’escalat a producció industrial, ha portat a la creació de sistemes experts i simuladors de compressió. En la present tesis, s’optimitza el sistema expert de diagrama SeDeM i es contrasta amb compressions industrials amb el simulador Styl’One. En primer lloc, es proposa una modificació en la metodologia per la determinació del paràmetre de l’Índex de cohesivitat del diagrama SeDeM, l’únic paràmetre que té en compte la compactabilitat de la mescla. Aquest paràmetre presentava desviacions per les mescles pulverulentes amb una densitat aparent molt elevada o molt baixa. També s’augmenta el nombre de paràmetres del SeDeM, afegint dos paràmetres mecànics en relació a la lubrificació. Aquests paràmetres són el punt de fusió (Mp) i la força d’ejecció (Fe). Els resultats del sistema expert de diagrama SeDeM són contrastats amb els resultats de compressió en condicions industrials. Cinc formulacions diferents es comprimeixen sota diferents perfils de compressió utilitzant un simulador de compressió industrial Styl’One. Els resultats indiquen que un ajust del pes del comprimit en funció de la densitat aparent de la pólvora permet la obtenció de comprimits de dimensions similars, evitant les desviacions esmentades. Fet demostrat en el desenvolupament d’una formulació la comparació de cel·luloses microcristal·lines de diferents fabricants i graus o tipus. També s’ha establert una metodologia ràpida i accessible per la determinació dels dos nous paràmetres mecànics i una conversió del valor experimental al valor radi. Fet que permet la seva integració en el sistema SeDeM. Els dos paràmetres integrats han demostrat tenir una rellevància en els resultats de la compressió i han permès augmentar el valor de l’índex de fiabilitat del SeDeM. Finalment, tres fórmules dissenyades per compressió directa i dues per granulació via humida es comprimeixen amb l’Styl’One simulant diferents perfils de compressió (Korsch XL 400, Fette 2909, Fette 3100, Kilian RX 47 i Kilian S 250) de màquines de comprimir rotatòries sota condicions de compressió diferents. Els resultats de la compressió demostren la precisió dels resultats previs obtinguts en els diagrames SeDeM i indiquen una relació entre valors deficients per l’Índex de Carr i l’Índex d’esponjositat i problemes d’exfoliació durant la compressió. L’addició d’una força de precompressió permet solucionar els problemes d’exfoliació en la majoria de les Referències. Els resultats indiquen que les referències desenvolupades per compressió directa presenten uns resultats equiparables o superiors a les referències per granulació via humida, amb un impacte econòmic menor (temps i costos) en el seu desenvolupament. En conclusió, s’ha optimitzat el sistema SeDeM, corregint desviacions i augmentant l’índex de fiabilitat. El simulador de compressió Styl’One ha posat de manifest la precisió i robustesa del sistema SeDeM en la selecció de la formulació més òptima i permet seleccionar les condicions de compressió més òptimes, maximitzar l’eficiència del procés i facilitar l’escalat.[eng] Tablets are the most common solid oral dosage forms. Direct Compression (DC) is a good methodology due to its low manufacturing times and a reduced number of steps. However, this methodology requires powders which display adequate properties in order to be compressible. The need of a swift design of pharmaceutical formulations which fulfill the compression standards and the scale-up led to create expert systems and press simulators. In this thesis, the expert system SeDeM is optimized: a new methodology to determine the Cohesion Index is stablished and two new mechanical parameters are introduced (Melting point and Ejection Force). Then, the results obtained from the SeDeM diagram are compared against the results obtained from the Styl’ONE press simulator in simulated industrial conditions. The results indicates that the new methodology is more accurate and it has been demonstrated in the development of a formula, and the comparison of different Microcrystalline Celluloses from different manufacturers. The inclusion of the two new mechanical parameters has increased the SeDeM’s reliability index. Then, three formulas developed by DC and two developed by wet granulation were compressed by means of Styl’One press simulator. Five different rotatory press’ compression profiles were simulated (Korsch XL 400, Fette 2090, Fette 3100, Kilian RX 47 I Kilian S 250) under different compression conditions. The results show the accuracy of SeDeM system and seems to indicate a correlation between Carr’s Index and Inter particle porosity Index, low radius values and capping phenomenon during the compression process. These issues where solved by applying a pre-compression Force. Moreover, the DC formulas display results similar or higher than the wet granulation formulas. In conclusion, the SeDeM expert system has been optimized, correcting the Cohesion Index deviations and increasing the reliability index by adding two mechanical parameters. The Styl’One press simulator has enabled to highlight the SeDeM system’s accuracy and robustness on choosing the most optimal formulation as well as the most optimal compression conditions in order to maximize the process’ efficiency and the scale-up
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Aplicació de la simulació de compressió a l’estudi del comportament i optimització de comprimits elaborats per compressió directa utilitzant el sistema expert SeDeM
'Edicions de la Universitat de Barcelona', 2019Co-Authors: Nofrerias Roig IsaacAbstract:El comprimit és la forma farmacèutica més freqüent al mercat. El procés tecnològic d’elaboració de comprimits d’elecció és la compressió directa perquè permet un estalvi en el nombre d’etapes. Tanmateix, aquest procés requereix que les pólvores presentin unes característiques adequades per la compressió per se. La necessitat de dissenyar ràpidament una fórmula farmacèutica que compleixi els estàndards de compressió i l’escalat a producció industrial, ha portat a la creació de sistemes experts i simuladors de compressió. En la present tesis, s’optimitza el sistema expert de diagrama SeDeM i es contrasta amb compressions industrials amb el simulador Styl’One. En primer lloc, es proposa una modificació en la metodologia per la determinació del paràmetre de l’Índex de cohesivitat del diagrama SeDeM, l’únic paràmetre que té en compte la compactabilitat de la mescla. Aquest paràmetre presentava desviacions per les mescles pulverulentes amb una densitat aparent molt elevada o molt baixa. També s’augmenta el nombre de paràmetres del SeDeM, afegint dos paràmetres mecànics en relació a la lubrificació. Aquests paràmetres són el punt de fusió (Mp) i la força d’ejecció (Fe). Els resultats del sistema expert de diagrama SeDeM són contrastats amb els resultats de compressió en condicions industrials. Cinc formulacions diferents es comprimeixen sota diferents perfils de compressió utilitzant un simulador de compressió industrial Styl’One. Els resultats indiquen que un ajust del pes del comprimit en funció de la densitat aparent de la pólvora permet la obtenció de comprimits de dimensions similars, evitant les desviacions esmentades. Fet demostrat en el desenvolupament d’una formulació la comparació de cel·luloses microcristal·lines de diferents fabricants i graus o tipus. També s’ha establert una metodologia ràpida i accessible per la determinació dels dos nous paràmetres mecànics i una conversió del valor experimental al valor radi. Fet que permet la seva integració en el sistema SeDeM. Els dos paràmetres integrats han demostrat tenir una rellevància en els resultats de la compressió i han permès augmentar el valor de l’índex de fiabilitat del SeDeM. Finalment, tres fórmules dissenyades per compressió directa i dues per granulació via humida es comprimeixen amb l’Styl’One simulant diferents perfils de compressió (Korsch XL 400, Fette 2909, Fette 3100, Kilian RX 47 i Kilian S 250) de màquines de comprimir rotatòries sota condicions de compressió diferents. Els resultats de la compressió demostren la precisió dels resultats previs obtinguts en els diagrames SeDeM i indiquen una relació entre valors deficients per l’Índex de Carr i l’Índex d’esponjositat i problemes d’exfoliació durant la compressió. L’addició d’una força de precompressió permet solucionar els problemes d’exfoliació en la majoria de les Referències. Els resultats indiquen que les referències desenvolupades per compressió directa presenten uns resultats equiparables o superiors a les referències per granulació via humida, amb un impacte econòmic menor (temps i costos) en el seu desenvolupament. En conclusió, s’ha optimitzat el sistema SeDeM, corregint desviacions i augmentant l’índex de fiabilitat. El simulador de compressió Styl’One ha posat de manifest la precisió i robustesa del sistema SeDeM en la selecció de la formulació més òptima i permet seleccionar les condicions de compressió més òptimes, maximitzar l’eficiència del procés i facilitar l’escalat.Tablets are the most common solid oral dosage forms. Direct Compression (DC) is a good methodology due to its low manufacturing times and a reduced number of steps. However, this methodology requires powders which display adequate properties in order to be compressible. The need of a swift design of pharmaceutical formulations which fulfill the compression standards and the scale-up led to create expert systems and press simulators. In this thesis, the expert system SeDeM is optimized: a new methodology to determine the Cohesion Index is stablished and two new mechanical parameters are introduced (Melting point and Ejection Force). Then, the results obtained from the SeDeM diagram are compared against the results obtained from the Styl’ONE press simulator in simulated industrial conditions. The results indicates that the new methodology is more accurate and it has been demonstrated in the development of a formula, and the comparison of different Microcrystalline Celluloses from different manufacturers. The inclusion of the two new mechanical parameters has increased the SeDeM’s reliability index. Then, three formulas developed by DC and two developed by wet granulation were compressed by means of Styl’One press simulator. Five different rotatory press’ compression profiles were simulated (Korsch XL 400, Fette 2090, Fette 3100, Kilian RX 47 I Kilian S 250) under different compression conditions. The results show the accuracy of SeDeM system and seems to indicate a correlation between Carr’s Index and Inter particle porosity Index, low radius values and capping phenomenon during the compression process. These issues where solved by applying a pre-compression Force. Moreover, the DC formulas display results similar or higher than the wet granulation formulas. In conclusion, the SeDeM expert system has been optimized, correcting the Cohesion Index deviations and increasing the reliability index by adding two mechanical parameters. The Styl’One press simulator has enabled to highlight the SeDeM system’s accuracy and robustness on choosing the most optimal formulation as well as the most optimal compression conditions in order to maximize the process’ efficiency and the scale-up
Giovanni Lucchetta - One of the best experts on this subject based on the ideXlab platform.
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Effect of ultrasound vibration on the Ejection friction in microinjection molding
The International Journal of Advanced Manufacturing Technology, 2018Co-Authors: Davide Masato, Marco Sorgato, Giovanni LucchettaAbstract:The form accuracy of microinjection-molded parts is significantly affected by the friction at the interface with the mold during the Ejection phase. In this work, an ultrasound-assisted Ejection system was designed and tested for different polymers (PS, COC, and POM) and mold topographies. The proposed innovative solution aims at reducing the Ejection friction by decreasing the adhesion component of the frictional Force, which is controlled by the real contact area generated during the filling phase of the injection molding process. The experiments indicate a positive effect of ultrasound vibration on the friction Force values acquired during Ejection, with a maximum reduction of 16% for PS. The effect depends on polymer selection and it increases for higher mold roughness. Moreover, the combined effect on the Ejection Force of mold surface roughness, melt viscosity during filling and polymer elastic modulus at Ejection was modeled to the experimental data. This demonstrated that the effect of ultrasound vibration on the Ejection friction reduction is due to the heating of the contact interface and the consequent reduction of the polymer elastic modulus.
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effects of machined cavity texture on Ejection Force in micro injection molding
Precision Engineering-journal of The International Societies for Precision Engineering and Nanotechnology, 2017Co-Authors: Marco Sorgato, Davide Masato, Giovanni LucchettaAbstract:Abstract The friction Force developed in the demolding phase of the micro injection molding process is mainly determined by mold surface finish, which affects the tribological phenomena occurring at the polymer–tool interface. In this work, the effects on the Ejection Force of two cavity surfaces machined with different technologies (viz. micro milling and micro electro discharge machining), but with similar value of Ra , were investigated. The relations between different surface topography parameters and the Ejection Force were then analyzed, in order to identify the parameters that most appropriately describe the friction at the polymer–tool interface. The experimental results showed the strong interactions between the mold surface texture and the micro injection molding process parameters that promote the replication, such as mold temperature and holding pressure. The different machining technologies generated two mold textures that have a similar value of Ra , but their influence on friction can be properly described only using several other surface topography parameters.
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Surface footprint in molds micromilling and effect on part demoldability in micro injection molding
Journal of Manufacturing Processes, 2017Co-Authors: Paolo Parenti, Marco Sorgato, Davide Masato, Giovanni Lucchetta, Massimiliano AnnoniAbstract:Accuracy of micromilled molds play an important role in complex process chains enabling mass production of polymer micro components, such as lab-on-chips, fabricated by micro injection molding. Surface footprint of micromilling is defined as the technological signature left by machining process on the generated mold surface. This is sensitive to selected tools and machining parameters and, when not controlled properly, can badly affect mold topography and functionality (e.g. part demoldability). In case of complex mold geometry, the impact of micromilling footprint increases, in particular during the demolding phase due to the friction generated by the polymer shrinking around cores. This work studies these effects on molds characterized by sub-millimetric cylindrical cores. A physical and statistical modeling was developed to provide deep insights about the effects of milling strategies and cutting parameters on the generated footprint on the mold cores. These effects are investigated by machining cylindrical pins whose roughness and surface form errors, caused by static deflection of tool and parts, were controlled in the range of Sa = 150–400 μm and ΔRmax = 1–10 μm (profile radial deviation), respectively. Micro injection molding experiments proved that mold topography has a relevant effect on the Ejection Force. The demolding Force generated by a specifically developed polystyrene micro part reached the highest value with the mold machined with the most unfavorable milling conditions. Proper controlling of machine parameters and conditions led to a reduction greater than 60% of the demolding Force peak, confirming the feasibility of the conjunct approach to processes optimization. The results of this work move a step forward into the integrated optimization of micro manufacturing process chains.
Massimiliano Annoni - One of the best experts on this subject based on the ideXlab platform.
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Surface footprint in molds micromilling and effect on part demoldability in micro injection molding
Journal of Manufacturing Processes, 2017Co-Authors: Paolo Parenti, Marco Sorgato, Davide Masato, Giovanni Lucchetta, Massimiliano AnnoniAbstract:Accuracy of micromilled molds play an important role in complex process chains enabling mass production of polymer micro components, such as lab-on-chips, fabricated by micro injection molding. Surface footprint of micromilling is defined as the technological signature left by machining process on the generated mold surface. This is sensitive to selected tools and machining parameters and, when not controlled properly, can badly affect mold topography and functionality (e.g. part demoldability). In case of complex mold geometry, the impact of micromilling footprint increases, in particular during the demolding phase due to the friction generated by the polymer shrinking around cores. This work studies these effects on molds characterized by sub-millimetric cylindrical cores. A physical and statistical modeling was developed to provide deep insights about the effects of milling strategies and cutting parameters on the generated footprint on the mold cores. These effects are investigated by machining cylindrical pins whose roughness and surface form errors, caused by static deflection of tool and parts, were controlled in the range of Sa = 150–400 μm and ΔRmax = 1–10 μm (profile radial deviation), respectively. Micro injection molding experiments proved that mold topography has a relevant effect on the Ejection Force. The demolding Force generated by a specifically developed polystyrene micro part reached the highest value with the mold machined with the most unfavorable milling conditions. Proper controlling of machine parameters and conditions led to a reduction greater than 60% of the demolding Force peak, confirming the feasibility of the conjunct approach to processes optimization. The results of this work move a step forward into the integrated optimization of micro manufacturing process chains.
Marco Sorgato - One of the best experts on this subject based on the ideXlab platform.
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Effect of ultrasound vibration on the Ejection friction in microinjection molding
The International Journal of Advanced Manufacturing Technology, 2018Co-Authors: Davide Masato, Marco Sorgato, Giovanni LucchettaAbstract:The form accuracy of microinjection-molded parts is significantly affected by the friction at the interface with the mold during the Ejection phase. In this work, an ultrasound-assisted Ejection system was designed and tested for different polymers (PS, COC, and POM) and mold topographies. The proposed innovative solution aims at reducing the Ejection friction by decreasing the adhesion component of the frictional Force, which is controlled by the real contact area generated during the filling phase of the injection molding process. The experiments indicate a positive effect of ultrasound vibration on the friction Force values acquired during Ejection, with a maximum reduction of 16% for PS. The effect depends on polymer selection and it increases for higher mold roughness. Moreover, the combined effect on the Ejection Force of mold surface roughness, melt viscosity during filling and polymer elastic modulus at Ejection was modeled to the experimental data. This demonstrated that the effect of ultrasound vibration on the Ejection friction reduction is due to the heating of the contact interface and the consequent reduction of the polymer elastic modulus.
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effects of machined cavity texture on Ejection Force in micro injection molding
Precision Engineering-journal of The International Societies for Precision Engineering and Nanotechnology, 2017Co-Authors: Marco Sorgato, Davide Masato, Giovanni LucchettaAbstract:Abstract The friction Force developed in the demolding phase of the micro injection molding process is mainly determined by mold surface finish, which affects the tribological phenomena occurring at the polymer–tool interface. In this work, the effects on the Ejection Force of two cavity surfaces machined with different technologies (viz. micro milling and micro electro discharge machining), but with similar value of Ra , were investigated. The relations between different surface topography parameters and the Ejection Force were then analyzed, in order to identify the parameters that most appropriately describe the friction at the polymer–tool interface. The experimental results showed the strong interactions between the mold surface texture and the micro injection molding process parameters that promote the replication, such as mold temperature and holding pressure. The different machining technologies generated two mold textures that have a similar value of Ra , but their influence on friction can be properly described only using several other surface topography parameters.
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Surface footprint in molds micromilling and effect on part demoldability in micro injection molding
Journal of Manufacturing Processes, 2017Co-Authors: Paolo Parenti, Marco Sorgato, Davide Masato, Giovanni Lucchetta, Massimiliano AnnoniAbstract:Accuracy of micromilled molds play an important role in complex process chains enabling mass production of polymer micro components, such as lab-on-chips, fabricated by micro injection molding. Surface footprint of micromilling is defined as the technological signature left by machining process on the generated mold surface. This is sensitive to selected tools and machining parameters and, when not controlled properly, can badly affect mold topography and functionality (e.g. part demoldability). In case of complex mold geometry, the impact of micromilling footprint increases, in particular during the demolding phase due to the friction generated by the polymer shrinking around cores. This work studies these effects on molds characterized by sub-millimetric cylindrical cores. A physical and statistical modeling was developed to provide deep insights about the effects of milling strategies and cutting parameters on the generated footprint on the mold cores. These effects are investigated by machining cylindrical pins whose roughness and surface form errors, caused by static deflection of tool and parts, were controlled in the range of Sa = 150–400 μm and ΔRmax = 1–10 μm (profile radial deviation), respectively. Micro injection molding experiments proved that mold topography has a relevant effect on the Ejection Force. The demolding Force generated by a specifically developed polystyrene micro part reached the highest value with the mold machined with the most unfavorable milling conditions. Proper controlling of machine parameters and conditions led to a reduction greater than 60% of the demolding Force peak, confirming the feasibility of the conjunct approach to processes optimization. The results of this work move a step forward into the integrated optimization of micro manufacturing process chains.
Douglas E. Smith - One of the best experts on this subject based on the ideXlab platform.
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Experimental comparison of Forces resisting viral DNA packaging and driving DNA Ejection
Physical Review E, 2017Co-Authors: Nicholas Keller, Paul J. Jardine, Zachary T Berndsen, Douglas E. SmithAbstract:We compare Forces resisting DNA packaging and Forces driving DNA Ejection in bacteriophage phi29 with theoretical predictions. Ejection of DNA from prohead-motor complexes is triggered by heating complexes after in vitro packaging and Force is inferred from the suppression of Ejection by applied osmotic pressure. Ejection Force from $0%$ to $80%$ filling is found to be in quantitative agreement with predictions of a continuum mechanics model that assumes a repulsive DNA-DNA interaction potential based on DNA condensation studies and predicts an inverse-spool conformation. Force resisting DNA packaging from $\ensuremath{\sim}80%$ to $100%$ filling inferred from optical tweezers studies is also consistent with the predictions of this model. The striking agreement with these two different measurements suggests that the overall energetics of DNA packaging is well described by the model. However, since electron microscopy studies of phi29 do not reveal a spool conformation, our findings suggest that the spool model overestimates the role of bending rigidity and underestimates the role of intrastrand repulsion. Below $\ensuremath{\sim}80%$ filling the inferred Forces resisting packaging are unexpectedly lower than the inferred Ejection Forces, suggesting that in this filling range the Forces are less accurately determined or strongly temperature dependent.