Numerical and experimental investigation of capping mechanisms during pharmaceutical tablet compaction

Wu, Chuan‐Yu; Hancock, Bruno C.; Mills, Andrew R.; Bentham, A.C.; Best, SM; Elliott, James A.

doi:10.1016/j.powtec.2006.12.017

Cited by 155 publications

(87 citation statements)

References 26 publications

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“…The parameters were adapted to the specifications of the monograph for tablets given in the Brazilian Pharmacopoeia 2010. The hardness values of >3.5Kgf, the good results obtained in the friability test and the non-occurrence of capping, cracks or lamination demonstrated the mechanical strength of the cores (Wu et al, 2008). The omeprazole contents were determined by HPLC and were in agreement with the compositions detailed in Table I.…”

Section: Evaluation Of Mixtures and Mini-tablets Obtainedsupporting

confidence: 70%

Development of a multiparticulate system containing enteric-release mini-tablets of omeprazole

Filho¹,

Andreazza²,

Sato³

et al. 2014

Braz. J. Pharm. Sci.

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The main aim of this study was to develop a multiparticulate system containing mini-tablets of omeprazole formulated with an enteric polymer with pH-dependent solubility. Pre-formulation studies showed good flow and compaction capacity, leading to the production ofhigh quality mini-tablets. The mini-tablets were coated in a fluidized bed with hydroxypropylmethylcellulose /Eudragit ® L30D55 and packed into hard gelatin capsules. The dissolution profile showed gastro-resistance and zero-order kinetics. The dissolution profile for the formulation containing lactose as the diluent and coated with 12% (tablet weight gain) of polymer was similar to that ofthe reference drug.Uniterms: Multiparticulate system/modified release. Enteric release mini-tablets/development. Enteric release mini-tablets/evaluation. Omeprazole/dissolution. O presente trabalho teve como objetivo desenvolver e avaliar um sistema multiparticulado de liberação modificada, composto por mini-comprimidos revestidos com polímero de liberação pH-dependente, utilizando como fármaco modelo o omeprazol. Os mini-comprimidos (diâmetro de 2,5 mm) foram obtidos em máquina de compresssão excêntrica, revestidos em leito fluidizado com hidroxipropilmetilcelulose/ Eudragit ® L30D55 e, em seguida, acondicionados em cápsulas gelatinosas duras. A partir dos resultados obtidos no perfil de dissolução foi possível demonstrar a liberação gastro-resistente e comportamento cinético de ordem zero. A formulação contendo lactose como diluente, com revestimento de 12% de polímero, demonstrou semelhança com o medicamento referência.Unitermos: Sistema multiparticulado/liberação modificada. Mini-comprimidos de liberação entérica/ desenvolvimento. Mini-comprimidos de liberação entérica/avaliação. Omeprazol/dissolução.

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Section: Evaluation Of Mixtures and Mini-tablets Obtainedsupporting

confidence: 70%

Development of a multiparticulate system containing enteric-release mini-tablets of omeprazole

Filho¹,

Andreazza²,

Sato³

et al. 2014

Braz. J. Pharm. Sci.

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“…The effect of the residual stress distributions of tablets on tablet hardenss [1][2][3][4][5][6][7][8] and tableting failures such as capping and lamination 9,10) have been numerically investigated. The finite element method (FEM), in which the powder is modeled using the Drucker-Prager cap (DPC) model, [9][10][11][12][13][14] can be applied to modeling the deformation of pharmaceutical powders 11,15) and thus to simulate the residual stress distribution of tablets. Powders are modeled as continuum media in the FEM and the compaction process is identified by boundary-value analysis.…”

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confidence: 99%

“…[15][16][17][18][19] However, a few problems remain to be solved. Powders such as microcrystalline cellulose (MCC) and lactose (LAC) have been used to prepare the model formulation in many studies, 6,[9][10][11]15) despite actual pharmaceutical products including many different types of excipients. We previously demonstrated that the residual stress distribution of flat-faced tablets is affected by the formulation factors, such as the quantities of MCC, LAC and corn starch, and is closely related to tablet characteristics, such as the tensile strength and disintegration time.…”

mentioning

confidence: 99%

“…It is likely that the tablet shape affects the stress distribution remaining in the tablets, 3,10) and thereby critical pharmaceutical characteristics. The present study investigates the effect of the tablet shape identified by the surface curvature on the residual stress distribution of tablets that were prepared according to pragmatic formulation and process variables.…”

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confidence: 99%

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Numerical Investigation of the Residual Stress Distribution of Flat-Faced and Convexly Curved Tablets Using the Finite Element Method

Otoguro

Hayashi

Miura

et al. 2015

CHEMICAL & PHARMACEUTICAL BULLETIN

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The stress distribution of tablets after compression was simulated using a finite element method, where the powder was defined by the Drucker-Prager cap model. The effect of tablet shape, identified by the surface curvature, on the residual stress distribution was investigated. In flat-faced tablets, weak positive shear stress remained from the top and bottom die walls toward the center of the tablet. In the case of the convexly curved tablet, strong positive shear stress remained on the upper side and in the intermediate part between the die wall and the center of the tablet. In the case of x-axial stress, negative values were observed for all tablets, suggesting that the x-axial force always acts from the die wall toward the center of the tablet. In the flat tablet, negative x-axial stress remained from the upper edge to the center bottom. The x-axial stress distribution differed between the flat and convexly curved tablets. Weak stress remained in the y-axial direction of the flat tablet, whereas an upward force remained at the center of the convexly curved tablet. By employing multiple linear regression analysis, the mechanical properties of the tablets were predicted accurately as functions of their residual stress distribution. However, the multiple linear regression prediction of the dissolution parameters of acetaminophen, used here as a model drug, was limited, suggesting that the dissolution of active ingredients is not a simple process; further investigation is needed to enable accurate predictions of dissolution parameters. Key words tablet shape; simulation; mathematical model; residual stress; finite element method; multiple linear regression Tablets are the most common and popular dosage form of drug administration. Tablets are generally manufactured by compressing a mixture of dry powders or granules using metal dies and punches. Various stresses remain on the surface and in the interior of tablets after the compression. The effect of the residual stress distributions of tablets on tablet hardenss [1][2][3][4][5][6][7][8] and tableting failures such as capping and lamination 9,10) have been numerically investigated. The finite element method (FEM), in which the powder is modeled using the Drucker-Prager cap (DPC) model, [9][10][11][12][13][14] can be applied to modeling the deformation of pharmaceutical powders 11,15) and thus to simulate the residual stress distribution of tablets. Powders are modeled as continuum media in the FEM and the compaction process is identified by boundary-value analysis. The DPC model is often applied to the analysis of the stress distribution and relative-density changes of the tablets during the tableting process. In examples of the use of the DPC model, Han et al. 12) reported that the density distributions of the tablets were affected by the punch geometry while Wu et al. 9,10) described how tablet failure is more likely to be associated with a band of intensive shear stress generated during the decompression of tablets. Additionally, the density distribution pa...

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“…For instance, tablet failure, in particular capping, is more likely to be associated with an intensive shear band formed during the decompression stage. 1,2) Therefore, controlling the residual stress distribution of tablets is crucial in pharmaceutical design.…”

mentioning

confidence: 99%

Effect of Process Variables on the Drucker–Prager Cap Model and Residual Stress Distribution of Tablets Estimated by the Finite Element Method

Hayashi

Otoguro

Miura

et al. 2014

CHEMICAL & PHARMACEUTICAL BULLETIN

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A multivariate statistical technique was applied to clarify the causal correlation between variables in the manufacturing process and the residual stress distribution of tablets. Theophylline tablets were prepared according to a Box-Behnken design using the wet granulation method. Water amounts (X 1 ), kneading time (X 2 ), lubricant-mixing time (X 3 ), and compression force (X 4 ) were selected as design variables. The DruckerPrager cap (DPC) model was selected as the method for modeling the mechanical behavior of pharmaceutical powders. Simulation parameters, such as Young's modulus, Poisson rate, internal friction angle, plastic deformation parameters, and initial density of the powder, were measured. Multiple regression analysis demonstrated that the simulation parameters were significantly affected by process variables. The constructed DPC models were fed into the analysis using the finite element method (FEM), and the mechanical behavior of pharmaceutical powders during the tableting process was analyzed using the FEM. The results of this analysis revealed that the residual stress distribution of tablets increased with increasing X 4 . Moreover, an interaction between X 2 and X 3 also had an effect on shear and the x-axial residual stress of tablets. Bayesian network analysis revealed causal relationships between the process variables, simulation parameters, residual stress distribution, and pharmaceutical responses of tablets. These results demonstrated the potential of the FEM as a tool to help improve our understanding of the residual stress of tablets and to optimize process variables, which not only affect tablet characteristics, but also are risks of causing tableting problems.Key words tablet; simulation; mathematical model; residual stress; processing; Bayesian networkVarious stresses, such as shear and axial stress, remain in tablets after the tableting process, because of the induction of elastic recovery. This type of stress, which is termed the residual stress distribution of the tablet, affects tablet characteristics and causes tableting problems. For instance, tablet failure, in particular capping, is more likely to be associated with an intensive shear band formed during the decompression stage.1,2) Therefore, controlling the residual stress distribution of tablets is crucial in pharmaceutical design.However, it is difficult to measure the residual stress distribution of tablets using analytical instruments. For this reason, the finite element method (FEM), in which the powder is modeled using the Drucker-Prager cap (DPC) model, is used to estimate the residual stress distribution of tablets.3,4) The FEM is a numerical analytical method that is well established for the modeling of the deformation of powders in various industries, such as compaction in ceramic industries, and for the analysis of pharmaceutical-powder compaction. 5,6) In the FEM, powders are modeled as continuum media and the compaction behavior is analyzed by solving boundary value problems.The DPC model is one of the continu...

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Numerical and experimental investigation of capping mechanisms during pharmaceutical tablet compaction

Cited by 155 publications

References 26 publications

Development of a multiparticulate system containing enteric-release mini-tablets of omeprazole

Development of a multiparticulate system containing enteric-release mini-tablets of omeprazole

Numerical Investigation of the Residual Stress Distribution of Flat-Faced and Convexly Curved Tablets Using the Finite Element Method

Effect of Process Variables on the Drucker–Prager Cap Model and Residual Stress Distribution of Tablets Estimated by the Finite Element Method

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