An integrated Quality by Design (QbD) approach towards design space definition of a blending unit operation by Discrete Element Method (DEM) simulation

Adam, Siegfried; Suzzi, Daniele; Radeke, Charles; Khinast, Johannes G.

doi:10.1016/j.ejps.2010.10.013

Cited by 98 publications

(48 citation statements)

References 39 publications

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“…In recent years, the drastic increase in affordable computational power has allowed DEM simulations to become a versatile tool for industrial applications (2). DEM simulations have been used in various industrial fields to study processes such as mixing (3), granule breakage (4), silo filling and discharge (5,6), or milling (7). In the pharmaceutical industry, DEM simulations have been applied for nearly all major particulate processes.…”

Section: Introductionmentioning

confidence: 99%

Experimental Analysis of Tablet Properties for Discrete Element Modeling of an Active Coating Process

et al. 2013

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Abstract. Coating of solid dosage forms is an important unit operation in the pharmaceutical industry. In recent years, numerical simulations of drug manufacturing processes have been gaining interest as process analytical technology tools. The discrete element method (DEM) in particular is suitable to model tabletcoating processes. For the development of accurate simulations, information on the material properties of the tablets is required. In this study, the mechanical parameters Young's modulus, coefficient of restitution (CoR), and coefficients of friction (CoF) of gastrointestinal therapeutic systems (GITS) and of activecoated GITS were measured experimentally. The dynamic angle of repose of these tablets in a drum coater was investigated to revise the CoF. The resulting values were used as input data in DEM simulations to compare simulation and experiment. A mean value of Young's modulus of 31.9 MPa was determined by the uniaxial compression test. The CoR was found to be 0.78. For both tablet-steel and tablet-tablet friction, active-coated GITS showed a higher CoF compared with GITS. According to the values of the dynamic angle of repose, the CoF was adjusted to obtain consistent tablet motion in the simulation and in the experiment. On the basis of this experimental characterization, mechanical parameters are integrated into DEM simulation programs to perform numerical analysis of coating processes.

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Section: Introductionmentioning

confidence: 99%

Experimental Analysis of Tablet Properties for Discrete Element Modeling of an Active Coating Process

et al. 2013

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“…(2) and (3), where σ is the standard deviation of the concentration, n is the number of samples, W i is the concentration of sample i, and W is the mean concentration of the samples [40].…”

Section: Blendingmentioning

confidence: 99%

“…The RSD may be affected by the sample size, and Lacey's Index (M) is a metric that corrects for these effects [40,41], given in Eq. (4), where the subscript s denotes a completely segregated mixture and the subscript r denotes a perfectly random mixture.…”

Section: Blendingmentioning

confidence: 99%

Discrete Element Modeling of Solid Dosage Manufacturing Processes

Barrasso

Ramachandran

2016

Methods in Pharmacology and Toxicology

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Solid dosage manufacturing primarily involves powder process operations, such as mixing, granulation, and compaction. A model-based approach can be used to develop a better scientific understanding of these processes and implement Quality by Design. These models must predict the critical quality attributes of the product based on process parameters, equipment geometry, and material properties. Discrete element modeling (DEM) is often used to capture mechanistic, particle-scale information, such as velocity and force profiles. In this chapter, recent literature studies that use the DEM to model solid dosage manufacturing processes will be presented and discussed.

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“…From the perspective of pharmaceutical engineers, mathematical modeling methods play a prominent role in implementing the QbD initiative to develop a pharmaceutical process. 5 In recent years, several contributions have been reported to develop new processes under the framework of QbD using modeling methods including first-principle models, 6,7 response surface models based on design of experiments 8,9,10 and multivariate statistical models. 2,11,12 For developing a tablet production process which consists of multiple units, it is difficult to establish a deterministic model to describe the process comprehensively.…”

Section: Introductionmentioning

confidence: 99%

Latent variable modeling to analyze the effects of process parameters on the dissolution of paracetamol tablet

Sun

Zhang

et al. 2016

Bioengineered

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The dissolution is one of the critical quality attributes (CQAs) of oral solid dosage forms because it relates to the absorption of drug. In this paper, the influence of raw materials, granules and process parameters on the dissolution of paracetamol tablet was analyzed using latent variable modeling methods. The variability in raw materials and granules was understood based on the principle component analysis (PCA), respectively. A multi-block partial least squares (MBPLS) model was used to determine the critical factors affecting the dissolution. The results showed that the binder amount, the post granulation time, the API content in granule, the fill depth and the punch tip separation distance were the critical factors with variable importance in the projection (VIP) values larger than 1. The importance of each unit of the whole process was also ranked using the block importance in the projection (BIP) index. It was concluded that latent variable models (LVMs) were very useful tools to extract information from the available data and improve the understanding on dissolution behavior of paracetamol tablet. The obtained LVMs were also helpful to propose the process design space and to design control strategies in the further research.

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An integrated Quality by Design (QbD) approach towards design space definition of a blending unit operation by Discrete Element Method (DEM) simulation

Cited by 98 publications

References 39 publications

Experimental Analysis of Tablet Properties for Discrete Element Modeling of an Active Coating Process

Experimental Analysis of Tablet Properties for Discrete Element Modeling of an Active Coating Process

Discrete Element Modeling of Solid Dosage Manufacturing Processes

Latent variable modeling to analyze the effects of process parameters on the dissolution of paracetamol tablet

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