Prediction of Tablet Characteristics from Residual Stress Distribution Estimated by the Finite Element Method

Otoguro

Miura

et al. 2014

Self Cite

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...

Section: Comparison Of the Fem With Experimental Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

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

Otoguro

Miura

et al. 2014

Self Cite

“…They demonstrated that the position of the breaking line significantly affected the breaking strength of scored tablets. Although numerous FEM simulation studies evaluating the powder compaction and mechanical strength of tablets have been reported, [5][6][7][8][9][10][11][12][13][14][15][16][17] very little is known regarding the mechanical adequacy of score shapes involving dividing strength, halving equality, and breaking strength. The aim of this study was to clarify the effect of score shapes on the essential characteristics of tablets by using FEM simulation.…”

mentioning

confidence: 99%

Mechanical Stress Simulation of Scored Tablets Based on the Finite Element Method and Experimental Verification

Okada

Onuki

et al. 2016

Self Cite

Scored tablets can be divided into equal halves for individual treatment of patients. However, the relationships between scored shapes and tablet characteristics such as the dividing strength, halving equality, and breaking strength are poorly understood. The purpose of this study was to simulate the mechanical stress distribution of scored tablets by using the finite element method (FEM). A runnel of triangle pole on the top surface of flat tablets was fabricated as the score shape. The depth and angle of the scores were selected as design variables. Elastic parameters such as a Young's modulus and a Poisson ratio for the model powder bed were measured. FEM simulation was then applied to the scored tablets, represented as a continuum elastic model. Stress distributions in the inner structure of the tablets were simulated after applying external force. The adequacy of the simulation was evaluated in experiments using scored tablets. As a result, we observed a relatively good agreement between the FEM simulation and the experiments, suggesting that FEM simulation is advantageous for designing scored tablets.

“…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. 20) Furthermore, we clarified the stochastic relationships between the tableting process variables, the DPC parameters, and the residual stress distribution of tablets by employing a Bayesian network (BN) analysis. 20) The BN model showed the probabilistic relationship between process variables, simulation parameters, tablet characteristics, and residual stress distributions.…”

mentioning

confidence: 99%

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

Otoguro

Miura

et al. 2015

Self Cite

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...