Continuous high-shear granulation: Mechanistic understanding of the influence of process parameters on critical quality attributes via elucidating the internal physical and chemical microstructure

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60461373%3A22340%2F19%3A43919143" target="_blank" >RIV/60461373:22340/19:43919143 - isvavai.cz</a>

Výsledek na webu

<a href="https://doi.org/10.1016/j.apt.2019.04.028" target="_blank" >https://doi.org/10.1016/j.apt.2019.04.028</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.apt.2019.04.028" target="_blank" >10.1016/j.apt.2019.04.028</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Continuous high-shear granulation: Mechanistic understanding of the influence of process parameters on critical quality attributes via elucidating the internal physical and chemical microstructure

Popis výsledku v původním jazyce

Over the past decade, continuous wet granulation has been emerging as a promising technology in drug product development. In this paper, the continuous high-shear mixer granulator, Lӧdige CoriMix® CM5, was investigated using a low-dose formulation with acetaminophen as the model drug. Design of experiments was deployed in conjunction with multivariate data analysis to explore the granulator design space and comprehensively understand the interrelation between process parameters and critical attributes of granules and tablets. Moreover, several complementary imaging techniques were implemented to unveil the underlying mechanisms of physical and chemical microstructure in affecting the tablet performance. The results indicated that L/S ratio and impeller speed outweighed materials feeding rate in modifying the granule and tablet properties. Increasing the degree of liquid saturation and mechanical shear input in the granulation system principally produced granules of larger size, smaller porosity, improved flowability and enhanced sphericity, which after compression generated tablets with slower disintegration process and drug release kinetics due to highly consolidated physical microstructure. Besides, in comparison to batch mixing, continuous mixing integrated with a conical mill enabled better powder de-agglomeration effect, thus accelerating the drug dissolution with increased surface area. © 2019

Název v anglickém jazyce

Continuous high-shear granulation: Mechanistic understanding of the influence of process parameters on critical quality attributes via elucidating the internal physical and chemical microstructure

Popis výsledku anglicky

Over the past decade, continuous wet granulation has been emerging as a promising technology in drug product development. In this paper, the continuous high-shear mixer granulator, Lӧdige CoriMix® CM5, was investigated using a low-dose formulation with acetaminophen as the model drug. Design of experiments was deployed in conjunction with multivariate data analysis to explore the granulator design space and comprehensively understand the interrelation between process parameters and critical attributes of granules and tablets. Moreover, several complementary imaging techniques were implemented to unveil the underlying mechanisms of physical and chemical microstructure in affecting the tablet performance. The results indicated that L/S ratio and impeller speed outweighed materials feeding rate in modifying the granule and tablet properties. Increasing the degree of liquid saturation and mechanical shear input in the granulation system principally produced granules of larger size, smaller porosity, improved flowability and enhanced sphericity, which after compression generated tablets with slower disintegration process and drug release kinetics due to highly consolidated physical microstructure. Besides, in comparison to batch mixing, continuous mixing integrated with a conical mill enabled better powder de-agglomeration effect, thus accelerating the drug dissolution with increased surface area. © 2019

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

20401 - Chemical engineering (plants, products)

Projekt

—

Návaznosti

S - Specificky vyzkum na vysokych skolach<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2019

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Advanced Powder Technology

ISSN

0921-8831

e-ISSN

—

Svazek periodika

30

Číslo periodika v rámci svazku

9

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

17

Strana od-do

1765-1781

Kód UT WoS článku

000474829300003

EID výsledku v databázi Scopus

2-s2.0-85067009312