Processo di granulazione ad umido
La granulazione è definita come il processo di trasformazione fisica delle dimensioni di una particella di polvere. Il meccanismo di funzionamento del processo di granulazione e il suo scale-up possono essere considerati come parte integrante dell’ingegneria quantitativa.
La granulazione ad umido è un processo mediante il quale piccole particelle polverulenti sono agglomerate, per mezzo di sostanze specifiche denominate leganti, in masse coerenti e stabili (granuli) in cui le particelle originali sono ancora identificabili. Essendo che le caratteristiche del granulato finale dipendono dalla perfetta combinazione di una serie di fattori (dimensioni delle polveri, viscosità della soluzione legante, angolo di contatto, tensione superficiale liquido-solido, quantità e modalità di aggiunta del legante, durata del processo e velocità di rotazione della girante) si può parlare di “progettazione delle particelle”.
La granulazione ad umido è considerato un meccanismo complesso perché è sviluppato in tre fasi, bagnatura e nucleazione, crescita e consolidazione, attrito e rottura, che avvengono simultaneamente nella “camera di processo” e che contribuisco ad influenzare quelle che poi saranno le proprietà dei granuli ottenuti.
La granulazione ad umido è l’operazione più comune in campo farmaceutico per prevenire la segregazione dei componenti in una miscela di polveri fini migliorando le caratteristiche di flowability, di compressibilità e di omogeneità, nonché per produrre sistemi capaci di veicolare molecole funzionali.
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Le linee di ricerca
Il gruppo TPP affronta lo studio dei fenomeni alla base del processo di granulazione ad umido e dei parametri operativi più rilevanti per l’ottimizzazione di processo e per l’ottenimento di prodotti granulati con le caratteristiche tecnologiche desiderate (buone proprietà di flusso, cinetiche di rilascio controllate delle molecole attive incorporate). Le nostre ricerche sono riassumibili in:
- Analisi fenomenologica degli stadi di granulazione
- Analisi dei parametri operativi
- Caratterizzazione del granulato
- Analisi dell’immagine
- Analisi texture
- Analisi delle proprietà di bulk
- Analisi del rilascio del principio attivo
Pubblicazioni relative:
Read More2019
Simone, Veronica De; Dalmoro, Annalisa; Lamberti, Gaetano; Caccavo, Diego; D'Amore, Matteo; Barba, Anna Angela
Effect of binder and load solubility properties on HPMC granules produced by wet granulation process Journal Article
In: Journal of Drug Delivery Science and Technology, vol. 49, pp. 513-520, 2019.
@article{Simone}2019,
title = {Effect of binder and load solubility properties on HPMC granules produced by wet granulation process},
author = {Veronica {De Simone} and Annalisa Dalmoro and Gaetano Lamberti and Diego Caccavo and Matteo D'Amore and Anna Angela Barba},
url = {https://www.sciencedirect.com/science/article/pii/S1773224718311043},
doi = {10.1016/j.jddst.2018.12.030},
year = {2019},
date = {2019-02-01},
journal = {Journal of Drug Delivery Science and Technology},
volume = {49},
pages = {513-520},
abstract = {Hydroxypropyl methylcellulose (HPMC) is one of the most important hydrophilic ingredients used in hydrogel matrices preparation (tablets or granules). In this work, HPMC was used to produce granules loaded with hydrophilic and hydrophobic active molecules to investigate their possible use as release dosage forms for pharmaceutical and nutraceutical applications. Unloaded and vitamins loaded HPMC granules were produced by wet granulation to investigate the effect of molecule solubility and granulation liquid type, on physical, mechanical and release properties. Water-soluble vitamin B12 and water-insoluble vitamin D2 were used as model molecules. Due to their different solubility, two granulation liquid phases were also used: distilled water for granules with B12, and ethanol-water for granules with D2. Results showed that use of ethanol in the liquid phase reduces the granulation yield and produces granules having a less defined shape, a smaller mean size, a less hard structure and a worse flowability. Moreover, ethanol slightly enhances the polymer erosion rate. Results also emphasized that the vitamins solubility does not affect either the physical and the mechanical properties of the produced granules. However, it plays a significant relevant role on the molecule release mechanism, being B12 and D2 were released by diffusion and erosion mechanism, respectively.},
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Hydroxypropyl methylcellulose (HPMC) is one of the most important hydrophilic ingredients used in hydrogel matrices preparation (tablets or granules). In this work, HPMC was used to produce granules loaded with hydrophilic and hydrophobic active molecules to investigate their possible use as release dosage forms for pharmaceutical and nutraceutical applications. Unloaded and vitamins loaded HPMC granules were produced by wet granulation to investigate the effect of molecule solubility and granulation liquid type, on physical, mechanical and release properties. Water-soluble vitamin B12 and water-insoluble vitamin D2 were used as model molecules. Due to their different solubility, two granulation liquid phases were also used: distilled water for granules with B12, and ethanol-water for granules with D2. Results showed that use of ethanol in the liquid phase reduces the granulation yield and produces granules having a less defined shape, a smaller mean size, a less hard structure and a worse flowability. Moreover, ethanol slightly enhances the polymer erosion rate. Results also emphasized that the vitamins solubility does not affect either the physical and the mechanical properties of the produced granules. However, it plays a significant relevant role on the molecule release mechanism, being B12 and D2 were released by diffusion and erosion mechanism, respectively.2018
Simone, Veronica De; Caccavo, Diego; Lamberti, Gaetano; D'Amore, Matteo; Barba, Anna Angela
Wet-granulation process: phenomenological analysis and process parameters optimization Journal Article
In: Powder Technology, vol. 340, pp. 411-419, 2018.
@article{Simone}2018b,
title = {Wet-granulation process: phenomenological analysis and process parameters optimization},
author = {Veronica {De Simone} and Diego Caccavo and Gaetano Lamberti and Matteo D'Amore and Anna Angela Barba},
url = {https://www.sciencedirect.com/science/article/pii/S0032591018307800},
doi = {10.1016/j.powtec.2018.09.053},
year = {2018},
date = {2018-12-01},
journal = {Powder Technology},
volume = {340},
pages = {411-419},
abstract = {Wet granulation is a size-enlargement process applied in many industrial fields, such as pharmaceutical, nutraceutical, zootecnichal, to improve flowability and compressibility properties of powders. In this work analysis of the particle size distribution (PSD) of granules was performed to understand the phenomena involved during the granulation process and to optimize the operating conditions. Hydroxypropyl methylcellulose (HPMC) granules were produced spraying distilled water as liquid binder on powders in a low-shear granulator. The experimental campaign was planned using the full factorial design statistical technique varying two factors (impeller rotation speed and binder flow rate), each at three intensities. PSDs of HPMC granules at different granulation times were obtained by an ad hoc dynamic image analysis device based on the free falling particle scheme. PSD measurements showed that wet granules size depends on the simultaneous presence of nucleation, agglomeration and breakage phenomena. The process parameters optimization was carried out using response surface methodology (RSM) and using the granulation yield (% w/w of wet granules within the size range 2000\textendash10,000 μm) as the main variable of interest.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Wet granulation is a size-enlargement process applied in many industrial fields, such as pharmaceutical, nutraceutical, zootecnichal, to improve flowability and compressibility properties of powders. In this work analysis of the particle size distribution (PSD) of granules was performed to understand the phenomena involved during the granulation process and to optimize the operating conditions. Hydroxypropyl methylcellulose (HPMC) granules were produced spraying distilled water as liquid binder on powders in a low-shear granulator. The experimental campaign was planned using the full factorial design statistical technique varying two factors (impeller rotation speed and binder flow rate), each at three intensities. PSDs of HPMC granules at different granulation times were obtained by an ad hoc dynamic image analysis device based on the free falling particle scheme. PSD measurements showed that wet granules size depends on the simultaneous presence of nucleation, agglomeration and breakage phenomena. The process parameters optimization was carried out using response surface methodology (RSM) and using the granulation yield (% w/w of wet granules within the size range 2000–10,000 μm) as the main variable of interest.Simone, Veronica De; Caccavo, Diego; Dalmoro, Annalisa; Lamberti, Gaetano; D'Amore, Matteo; Barba, Anna Angela
Inside the Phenomenological Aspects of Wet Granulation: Role of Process Parameters Book Chapter
In: Kyzas, George (Ed.): Chapter 5, IntechOpen, 2018, ISBN: 978-1-78984-308-8.
@inbook{Simone}2018c,
title = {Inside the Phenomenological Aspects of Wet Granulation: Role of Process Parameters},
author = {Veronica {De Simone} and Diego Caccavo and Annalisa Dalmoro and Gaetano Lamberti and Matteo D'Amore and Anna Angela Barba},
editor = {George Kyzas},
url = {https://www.intechopen.com/books/granularity-in-materials-science/inside-the-phenomenological-aspects-of-wet-granulation-role-of-process-parameters},
doi = {10.5772/intechopen.79840},
isbn = {978-1-78984-308-8},
year = {2018},
date = {2018-10-24},
publisher = {IntechOpen},
chapter = {5},
abstract = {Granulation is a size-enlargement process by which small particles are bonded, by means of various techniques, in coherent and stable masses (granules), in which the original particles are still identifiable. In wet granulation processes, the powder particles are aggregated through the use of a liquid phase called binder. The main purposes of size-enlargement process of a powder or mixture of powders are to improve technological properties and/or to realize suitable forms of commercial products. A modern and rational approach in the production of granular structures with tailored features (in terms of size and size distribution, flowability, mechanical and release properties, etc.) requires a deep understanding of phenomena involved during granules formation. By this knowledge, suitable predictive tools can be developed with the aim to choose right process conditions to be used in developing new formulations by avoiding or reducing costs for new tests. In this chapter, after introductive notes on granulation process, the phenomenological aspects involved in the formation of the granules with respect to the main process parameters are presented by experimental demonstration. Possible mathematical approaches in the granulation process description are also presented and the one involving the population mass balances equations is detailed.},
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Granulation is a size-enlargement process by which small particles are bonded, by means of various techniques, in coherent and stable masses (granules), in which the original particles are still identifiable. In wet granulation processes, the powder particles are aggregated through the use of a liquid phase called binder. The main purposes of size-enlargement process of a powder or mixture of powders are to improve technological properties and/or to realize suitable forms of commercial products. A modern and rational approach in the production of granular structures with tailored features (in terms of size and size distribution, flowability, mechanical and release properties, etc.) requires a deep understanding of phenomena involved during granules formation. By this knowledge, suitable predictive tools can be developed with the aim to choose right process conditions to be used in developing new formulations by avoiding or reducing costs for new tests. In this chapter, after introductive notes on granulation process, the phenomenological aspects involved in the formation of the granules with respect to the main process parameters are presented by experimental demonstration. Possible mathematical approaches in the granulation process description are also presented and the one involving the population mass balances equations is detailed.Simone, Veronica De; Dalmoro, Annalisa; Lamberti, Gaetano; Caccavo, Diego; D'Amore, Matteo; Barba, Anna Angela
HPMC granules by wet granulation process: Effect of vitamin load on physicochemical, mechanical and release properties Journal Article
In: Carbohydrate Polymers, vol. 181, pp. 939-947, 2018.
@article{{DeSimone}2018,
title = {HPMC granules by wet granulation process: Effect of vitamin load on physicochemical, mechanical and release properties},
author = {Veronica {De Simone} and Annalisa Dalmoro and Gaetano Lamberti and Diego Caccavo and Matteo D'Amore and Anna Angela Barba },
url = {http://www.sciencedirect.com/science/article/pii/S0144861717313425},
doi = {10.1016/j.carbpol.2017.11.056},
year = {2018},
date = {2018-02-01},
journal = {Carbohydrate Polymers},
volume = {181},
pages = {939-947},
abstract = {Due to its versatile properties, hydroxypropyl methylcellulose (HPMC) is largely used in many applications and deeply studied in the various elds such as pharmaceuticals, biomaterials, agriculture, food, water puri cation. In this work, vitamin B12 loaded HPMC granules were produced to investigate their potential application as nutraceutical products. To this aim the impact of vitamin load on physico-chemical, mechanical and release properties of granules, achieved by wet granulation process, was investigated. In particular, three different loads of B12 (1%, 2.3% and 5% w/w) were assayed. Unloaded granules (used as control) and loaded granules were dried, sieved, and then the suitable fraction for practical uses, 0.45\textendash2 mm in size, was fully characterized. Re- sults showed that the vitamin incorporation of 5% reduced the granulation performance in the range size of 0.45\textendash2 mm and led granules with higher porosity, more rigid and less elastic structures compared to unloaded granules and those loaded at 1% and 2.3% of B12. Vitamin release kinetics of fresh and aged granules were roughly found the same trends for all the prepared lots; however, the vitamin B12 was released more slowly when added with a load at 1% w/w, suggesting a better incorporation.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Due to its versatile properties, hydroxypropyl methylcellulose (HPMC) is largely used in many applications and deeply studied in the various elds such as pharmaceuticals, biomaterials, agriculture, food, water puri cation. In this work, vitamin B12 loaded HPMC granules were produced to investigate their potential application as nutraceutical products. To this aim the impact of vitamin load on physico-chemical, mechanical and release properties of granules, achieved by wet granulation process, was investigated. In particular, three different loads of B12 (1%, 2.3% and 5% w/w) were assayed. Unloaded granules (used as control) and loaded granules were dried, sieved, and then the suitable fraction for practical uses, 0.45–2 mm in size, was fully characterized. Re- sults showed that the vitamin incorporation of 5% reduced the granulation performance in the range size of 0.45–2 mm and led granules with higher porosity, more rigid and less elastic structures compared to unloaded granules and those loaded at 1% and 2.3% of B12. Vitamin release kinetics of fresh and aged granules were roughly found the same trends for all the prepared lots; however, the vitamin B12 was released more slowly when added with a load at 1% w/w, suggesting a better incorporation.2017
Caccavo, Diego; Cascone, Sara; Apicella, Pietro; Lamberti, Gaetano; Barba, Anna Angela
HPMC-Based Granules for Prolonged Release of Phytostrengtheners in Agriculture Journal Article
In: Chemical Engineering Communications, vol. 204, no 12, pp. 1333-1340, 2017, ISSN: 0098-6445.
@article{Caccavo2017b,
title = {HPMC-Based Granules for Prolonged Release of Phytostrengtheners in Agriculture},
author = {Diego Caccavo and Sara Cascone and Pietro Apicella and Gaetano Lamberti and Anna Angela Barba},
url = {http://www.tandfonline.com/doi/full/10.1080/00986445.2017.1362398},
doi = {10.1080/00986445.2017.1362398 },
issn = {0098-6445},
year = {2017},
date = {2017-12-01},
journal = {Chemical Engineering Communications},
volume = {204},
number = {12},
pages = {1333-1340},
abstract = {One of the main aim in agriculture is to guarantee soil wellness, which is a fundamental requirement to produce high quality crops with high yields. Focused on this aim, periodical administrations of nutrients or phytostrengtheners are often necessary. The most relevant disadvantages of these administrations are the high dosage number required and the low availability of the substance within the soil. For these reasons, a crucial goal to increase the economic and environmental sustainability of the cultivation process is to reduce the dosage number, which can be obtained increasing the active substance availability in the soil. A granular HPMC (HydroxyPropyl MethylCellulose) matrix, produced using the wet granulation process, was used to encapsulate a phytostrengthener and to guarantee its controlled release. The granular product was characterized in terms of granules properties and phytostrengtheners leaching within the soil. The results showed good flowability and mechanical properties of the granules as well as the possibility to reduce the product leaching with the phytostrengtheners encapsulation in the HPMC matrices.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
One of the main aim in agriculture is to guarantee soil wellness, which is a fundamental requirement to produce high quality crops with high yields. Focused on this aim, periodical administrations of nutrients or phytostrengtheners are often necessary. The most relevant disadvantages of these administrations are the high dosage number required and the low availability of the substance within the soil. For these reasons, a crucial goal to increase the economic and environmental sustainability of the cultivation process is to reduce the dosage number, which can be obtained increasing the active substance availability in the soil. A granular HPMC (HydroxyPropyl MethylCellulose) matrix, produced using the wet granulation process, was used to encapsulate a phytostrengthener and to guarantee its controlled release. The granular product was characterized in terms of granules properties and phytostrengtheners leaching within the soil. The results showed good flowability and mechanical properties of the granules as well as the possibility to reduce the product leaching with the phytostrengtheners encapsulation in the HPMC matrices.Simone, Veronica De; Dalmoro, Annalisa; Lamberti, Gaetano; D'Amore, Matteo; Barba, Anna Angela
Central Composite Design in HPMC granulation and correlations between product properties and process parameters Journal Article
In: New Journal of Chemistry, vol. 41, no 14, pp. 6504-6513, 2017.
@article{Simone}2017,
title = {Central Composite Design in HPMC granulation and correlations between product properties and process parameters},
author = {Veronica {De Simone} and Annalisa Dalmoro and Gaetano Lamberti and Matteo D'Amore and Anna Angela Barba},
url = {http://pubs.rsc.org/en/Content/ArticleLanding/2017/NJ/C7NJ01280B#!divAbstract},
doi = {10.1039/C7NJ01280B},
year = {2017},
date = {2017-07-21},
journal = {New Journal of Chemistry},
volume = {41},
number = {14},
pages = {6504-6513},
abstract = {Particulate solids have a great interest in many industrial fields for both marketing reasons and technological aspects. In this study granular systems were achieved by wet granulation process using HydroxyPropyl MethylCellulose (HPMC) and distilled water as binder phase. Particulates with a defined size (450-2000 µm) and good flowability together with a high granulation process yield to reduce manufacturing scrap, were produced. To this aim a bench scale low-shear rate granulator apparatus was used; three process parameters were varied (impeller rotation speed, binder volume at constant mass, binder flow rate) and, for each parameter, three intensities have been used. HPMC granules production was planned by the Central Composite Design (CCD) statistical protocol, which has allowed to minimize the number of runs to perform for obtaining information about the relationship between granules properties and process parameters. The produced granules were stabilized by a dedicated dynamic drying apparatus, then separated by sieving and then characterized in terms of size and flowability properties. The results of the experimental campaign have been used to develop semi-empirical correlations between granulated products properties and process parameters. A second-order polynomial law has shown the best comparison between experimental data and model predicted values. These correlations can constitute a reliable tool to know more on the effect of operative parameters changes in HMPC or similar particulate solids production.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Particulate solids have a great interest in many industrial fields for both marketing reasons and technological aspects. In this study granular systems were achieved by wet granulation process using HydroxyPropyl MethylCellulose (HPMC) and distilled water as binder phase. Particulates with a defined size (450-2000 µm) and good flowability together with a high granulation process yield to reduce manufacturing scrap, were produced. To this aim a bench scale low-shear rate granulator apparatus was used; three process parameters were varied (impeller rotation speed, binder volume at constant mass, binder flow rate) and, for each parameter, three intensities have been used. HPMC granules production was planned by the Central Composite Design (CCD) statistical protocol, which has allowed to minimize the number of runs to perform for obtaining information about the relationship between granules properties and process parameters. The produced granules were stabilized by a dedicated dynamic drying apparatus, then separated by sieving and then characterized in terms of size and flowability properties. The results of the experimental campaign have been used to develop semi-empirical correlations between granulated products properties and process parameters. A second-order polynomial law has shown the best comparison between experimental data and model predicted values. These correlations can constitute a reliable tool to know more on the effect of operative parameters changes in HMPC or similar particulate solids production.2015
Caccavo, Diego; Cascone, Sara; Amoroso, Maria Chiara; Apicella, Pietro; Lamberti, Gaetano; Barba, Anna Angela
Hydrogel-based Granular Phytostrengtheners for Prolonged Release: Production and Characterization Journal Article
In: Chemical Engineering Transaction, vol. 44, pp. 235–240, 2015.
@article{Caccavo2015,
title = {Hydrogel-based Granular Phytostrengtheners for Prolonged Release: Production and Characterization},
author = { Diego Caccavo and Sara Cascone and Maria Chiara Amoroso and Pietro Apicella and Gaetano Lamberti and Anna Angela Barba},
url = {http://www.aidic.it/cet/15/44/040.pdf},
doi = {10.3303/CET1544040},
year = {2015},
date = {2015-01-01},
journal = {Chemical Engineering Transaction},
volume = {44},
pages = {235--240},
abstract = {Soil wellness is an indispensable requirement to obtain fruits and vegetables with finest quality and with high yields. To the purpose, periodical administrations of nutrients, as well as phytostrengtheners could be required. Crucial goals to maximize the economic and environmental sustainability of the whole cultivation are the decrease of the dosages number together with the increase of the active substance availability within the soil. With these aims a controlled release phytostrengtheners encapsulated in a granular Hydroxypropyl methylcellulose matrix has been developed exploiting the wet granulation process. The granular product has been analyzed in terms of Particle Size Distribution (PSD), morphology and flowability. The results showed the effectiveness of the granulation process and the good flowability of the granules, highly desirable features for the product handling and commercialization.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Soil wellness is an indispensable requirement to obtain fruits and vegetables with finest quality and with high yields. To the purpose, periodical administrations of nutrients, as well as phytostrengtheners could be required. Crucial goals to maximize the economic and environmental sustainability of the whole cultivation are the decrease of the dosages number together with the increase of the active substance availability within the soil. With these aims a controlled release phytostrengtheners encapsulated in a granular Hydroxypropyl methylcellulose matrix has been developed exploiting the wet granulation process. The granular product has been analyzed in terms of Particle Size Distribution (PSD), morphology and flowability. The results showed the effectiveness of the granulation process and the good flowability of the granules, highly desirable features for the product handling and commercialization.2013
Barba, Anna Angela; Dalmoro, Annalisa; D'Amore, Matteo
Microwave assisted drying of cellulose derivative (HPMC) granular solids Journal Article
In: Powder Technology, vol. 237, pp. 581–585, 2013, ISSN: 00325910.
@article{Barba2013a,
title = {Microwave assisted drying of cellulose derivative (HPMC) granular solids},
author = { Anna Angela Barba and Annalisa Dalmoro and Matteo D'Amore},
url = {http://www.sciencedirect.com/science/article/pii/S0032591013000156},
doi = {10.1016/j.powtec.2012.12.060},
issn = {00325910},
year = {2013},
date = {2013-03-01},
journal = {Powder Technology},
volume = {237},
pages = {581--585},
abstract = {Drying constitutes a critical unit operation in the manufacturing of pharmaceutical powders and their associated products. In this work, the drying processes of cellulose derivative (hydroxypropyl methyl cellulose, HPMC) granules were investigated. Granules of HPMC powders were produced by a wet granulation process using a hydro-alcoholic solution as binder phase, then they were dried with different drying methods based on traditional (by convective heating) and innovative (by microwave heating) techniques. To compare drying kinetics, experimental data were fitted by Lewis equation obtaining drying coefficients, and time/temperature process parameters were investigated. Microwave assisted drying showed reduced process times and, under some conditions, it allowed no drastic process temperatures. Since granular solids have a great relevance in pharmaceutical solid dosage form preparations, novel methods of drying with better performances appeared an issue of great interest for industry.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Drying constitutes a critical unit operation in the manufacturing of pharmaceutical powders and their associated products. In this work, the drying processes of cellulose derivative (hydroxypropyl methyl cellulose, HPMC) granules were investigated. Granules of HPMC powders were produced by a wet granulation process using a hydro-alcoholic solution as binder phase, then they were dried with different drying methods based on traditional (by convective heating) and innovative (by microwave heating) techniques. To compare drying kinetics, experimental data were fitted by Lewis equation obtaining drying coefficients, and time/temperature process parameters were investigated. Microwave assisted drying showed reduced process times and, under some conditions, it allowed no drastic process temperatures. Since granular solids have a great relevance in pharmaceutical solid dosage form preparations, novel methods of drying with better performances appeared an issue of great interest for industry.2011
Caccavo, Diego; Cascone, Sara; Lamberti, Gaetano
Criteri per progettare e gestire il processo di granulazione Journal Article
In: ICP Rivista dell'Industria Chimica, vol. 4, pp. 74–78, 2011.
@article{Caccavo2011,
title = {Criteri per progettare e gestire il processo di granulazione},
author = { Diego Caccavo and Sara Cascone and Gaetano Lamberti},
year = {2011},
date = {2011-01-01},
journal = {ICP Rivista dell'Industria Chimica},
volume = {4},
pages = {74--78},
abstract = {Un approccio ingegneristico, basato su poche misure e ripetibili, e coaudiuvato dalla modellazione fisico-matematica, pu\`{o} essere di grande aiuto nella gestione del processo di granulazione.},
keywords = {},
pubstate = {published},
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}
Un approccio ingegneristico, basato su poche misure e ripetibili, e coaudiuvato dalla modellazione fisico-matematica, può essere di grande aiuto nella gestione del processo di granulazione.