The bending strength of tablets with a breaking line—Comparison of the results of an elastic and a "brittle cracking" finite element model with experimental findings

The aim of this work was to ascertain the influence of the position of the breaking line of bevel-edged tablets in a three-point bending test. Two different brands of commercially available, flat-round, bevel-edged tablets with a single central breaking line were studied. Breaking line positions tested, relative to the upper loading roll, were 0°, 22.5°, 45°, 67.5° and 90°. The breaking line faced either up- or downwards during the test. The practical results were compared with FEM results simulating similar test configurations. Tablets failed mainly across the failure plane, resulting in two tablet halves. An exception to this was found for tablets where the breaking line faced down and was positioned at an angle of 22.5° relative to the loading plane. Here the crack followed the breaking line in the centre of the tablets and only diverged towards the loading plane position at the edges of the tablets. The breaking line facing upwards resulted in a significantly higher tensile strength of the tablets compared to it facing downwards. However, with one exception, the orientation of the breaking line relative to the loading plane appeared not to affect the tensile strength values. A fully elastic FEM model indicated that both the position of the breaking line relative to the loading plane and as to whether the breaking line faced up- or downwards during the bending test would result in considerably different failure loads during practical experiments. The results also suggested that regardless of the breaking line position, when it is facing down crack propagation should start at the outer edges propagating towards the midpoint of the discs until failure occurs. Failure should hence always result in equal tablet halves, whereby the failure plane should coincide with the loading plane. Neither predictions fully reflected the practical behaviour of the tablets. Using a brittle cracking FEM model significantly larger tensile stresses for tablets with the breaking line positioned downwards at 0° or 22.5° relative to the loading plane were still predicted, but the differences between model and experimental values was greatly reduced. The remaining differences are more likely due to the inadequacy of the equation available to calculate the experimental tensile strength values. This equation cannot account for the presence of a breaking line and overestimates the thickness of the loading plane by the depth of the breaking line when in 0° or 22.5° position. If the depth of the breaking line is taken into account, the model predictions and the experimental findings are comparable. Also, in the brittle cracking FEM simulations the predicted crack propagation patterns were similar to those found in the experiments, and the model stress distributions across the lower surfaces were much more homogeneous and streamlined parallel to the loading plane. The brittle cracking model hence reflected the practicalities of the bending test more closely. The findings suggested that with the breaking line facing down fracture should always start in the centre of a tablet at its lower surface, initiated by the breaking line. Due to simultaneous development of larger stresses along the y-axis the tablet should still break into two equal halves along the loading plane, unless the position of the breaking line relative to the loading plane was 22.5°. In this case the tablet would fail by a mixed process, whereby failure would occur mainly along the breaking line, but due to simultaneous crack formation at the lower surface close to the bevel edge parallel to the loading plane the final breaking pattern would deviate from the breaking line about half-way from its centre, as seen in the practical experiments

Theoretical investigations into the influence of the position of a breaking line on the tensile failure of flat, round, bevel-edged tablets using finite element methodology (FEM) and its practical relevance for industrial tablet strength testing.

Flat, round tablets may have a breaking ("score") line. Pharmacopoeial tablet breaking load tests are diametral in their design, and industrially used breaking load testers often have automatic tablet feeding systems, which position the tablets between the loading platens of the machine with the breaking lines in random orientation to the applied load. The aim of this work was to ascertain the influence of the position of the breaking line in a diametral compression test using finite element methodology (FEM) and to compare the theoretical results with practical findings using commercially produced bevel-edged, scored tablets. Breaking line test positions at an angle of 0°, 22.5°, 45°, 67.5° and 90° relative to the loading plane were studied. FEM results obtained for fully elastic and elasto-plastic tablets were fairly similar, but they highlighted large differences in stress distributions depending on the position of the breaking line. The stress values at failure were predicted to be similar for tablets tested at an angle of 45° or above, whereas at lower test angles the predicted breaking loads were up to three times larger. The stress distributions suggested that not all breaking line angles would result in clean tensile failure. Practical results, however, did not confirm the differences in the predicted breaking loads, but they confirmed differences in the way tablets broke. The results suggest that it is not advisable to convert breaking loads obtained on scored tablets into tablet tensile strength values, and comparisons between different tablets or batches should carefully consider the orientation of the breaking line with respect to the loading plane, as the failure mechanisms appear to vary

Further Insight into Mechanisms of Ventricular Tachycardia from the Clinical Electrophysiology Laboratory

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72003/1/j.1540-8167.1991.tb01319.x.pd

The Bin Area Method: A Computationally Efficient Technique for Analysis of Ventricular and Atrial Intracardiac Electrograms

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74901/1/j.1540-8159.1990.tb02028.x.pd

Utjecaj različitih površinski aktivnih tvari i njihovih koncentracija na kontrolirano oslobađanje kaptoprila iz polimernih matriksa

Various methods are available to formulate water soluble drugs into sustained release dosage forms by retarding the dissolution rate. One of the methods used to control drug release and thereby prolong therapeutic activity is to use hydrophilic and lipophilic polymers. In this study, the effects of various polymers such as hydroxypropyl methylcellulose (HPMC), ethylcellulose (EC) and sodium carboxymethylcellulose (CMC) and surfactants (sodium lauryl sulphate, cetyltrimethylammonium bromide and Arlacel 60) on the release rate of captopril were investigated. The results showed that an increase in the amount of HPMC K15M resulted in reduction of the release rate of captopril from these matrices. When HPMC was partly replaced by NaCMC (the ratio of HPMC/NaCMC was 5:1), the release rate of the drug significantly decreased. However, there was no significant difference in release rate of captopril from matrices produced with ratios of 5:1 and 2:1 of HPMC/NaCMC. The presence of lactose in matrices containing HPMC and NaCMC increased the release rate of captopril. It was interesting to note that although partial replacement of HPMC by EC reduced the release rate of the drug (ratio of HPMC/EC 2:1), the release rate was increased when the ratio of HPMC/EC was reduced to 1:1. The effects of various surfactants on the release rate of captopril from HPMC/EC 1:1 matrices were also investigated. The results showed that the surfactants did not significantly change the release rate of the drug. Release data were examined kinetically and the ideal kinetic models were estimated for the drug release. The kinetic analysis of drug release data from various formulations showed that incorporation of surfactants in HPMC/EC matrices did not produce a zero-order release pattern.Postoje različite metode formuliranja vodotopljivih lijekova u dozirane ljekovite oblike s polaganim oslobađanjem. Jedan od načina postizanja kontroliranog otpuštanja, a prema tome i produljenog učinka je upotreba hidrofilnih i lipofilnih polimera. U ovom radu proučavan je utjecaj različitih polimera poput hidroksipropil metilceluloze (HPMC), etilceluloze (EC) i natrijeve soli karboksimetilceluloze (NaCMC) i površinski aktivnih tvari (natrijevog lauril-sulfata, cetiltrimetilamonijevog bromida i Arlacela 60) na oslobađanje kaptoprila. Rezultati pokazuju da povećanje količine HPMC K15M ima za posljedicu smanjenje oslobađanja kaptoprila iz matriksa. Ako se HPMC djelomično zamijeni s NaCMC (omjer HPMC/NaCMC 5:1), oslobađanje ljekovite tvari značajno se smanjuje. Međutim, nema značajne razlike u oslobađanju kaptoprila iz matriksa s omjerom HPMC/NaCMC 5:1 i 2:1. Prisutnost laktoze u matriksu koji sadrži HPMC i NaCMC povećalo je oslobađanje kaptoprila. Iako djelomična zamjena HPMC s EC smanjuje oslobađanje ljekovite tvari (omjer HPMC/EC 2:1), oslobađanje se povećava uz omjer HPMC/EC 1:1. Nadalje, ispitivan je utjecaj površinski aktivnih tvari na oslobađanje kaptoprila iz matriksa u kojima je omjer HPMC/EC (1:1). Može se zaključiti da površinski aktivne tvari ne utječu značajno na oslobađanje ljekovite tvari. U sklopu istraživanja određen je i kinetički model oslobađanja kaptoprila. Analiza kinetičkih podataka ukazuje da dodatak površinski aktivnih tvari u HPMC/EC matrikse ne slijedi kinetiku nultog reda

Impact of tunable oligophosphonates on barium sulfate crystallization

Calixarenes can be used as well-defined scaffolds for investigating structure–activity relationships of additives and their impact on crystallization. In this work, we present the crystal growth modification of barium sulfate by p-phosphonic acid calix[n]arenes that vary in size (n = 4, 5, 6, and 8) and thus vary in the size of the internal cavity for the same functionality in the upper rim. The tetrameric, hexameric, and octameric macrocycles induce nanoparticle formation with clear superstructure. In the case of the hexameric calix[6]arene, the initial mesocrystalline superstructure fuses over time to form almost hollow spheres, while the mesocrystals formed in the presence of the tetramer and octamer are stable over an extended period. The pentameric calix[5]arene forms more disordered aggregates of single crystals. Thermogravimetric data shows that a significant proportion of the mass of the barium sulfate-containing solid is the macrocycle, regardless of the choice of macrocycle

Prediction of inter-particle adhesion force from surface energy and surface roughness

Fine powder flow is a topic of great interest to industry, in particular for the pharmaceutical industry; a major concern being their poor flow behavior due to high cohesion. In this study, cohesion reduction, produced via surface modification, at the particle scale as well as bulk scale is addressed. The adhesion force model of Derjaguin-Muller-Toporov (DMT) was utilized to quantify the inter-particle adhesion force of both pure and surface modified fine aluminum powders (∼8 μm in size). Inverse Gas Chromatography was utilized for the determination of surface energy of the samples, and Atomic Force Microscopy was utilized to evaluate surface roughness of the powders. Surface modification of the original aluminum powders was done for the purpose of reduction in cohesiveness and improvement in flowability, employing either silane surface treatment or dry mechanical coating of nano-particles on the surface of original powders. For selected samples, the AFM was utilized for direct evaluation of the particle pull-off force. The results indicated that surface modification reduced the surface energy and altered the surface nano-roughness, resulting in drastic reduction of the inter-particle adhesion force. The particle bond number values were computed based on either the inter-particle adhesion force from the DMT model or the inter-particle pull-off force obtained from direct AFM measurements. Surface modification resulted in two to three fold reductions in the Bond number. In order to examine the influence of the particle scale property such as the Bond number on the bulk-scale flow characterization, Angle of Repose measurements were done and showed good qualitative agreements with the Bond number and acid/base surface characteristics of the powders. The results indicate a promising method that may be used to predict flow behavior of original (cohesive) and surface modified (previously cohesive) powders utilizing very small samples