The most useful dosage form taken from a patient's point of view is tablets because of its simplicity and portability (Takeuchi et al., 2004:132). Manufacturing of tablets can be done by wet granulation or direct compression of powders. For direct compression it is important that the powder has good particle flowability and compactability. Various methods to investigate these properties of the powder have been developed, which provide comparative indices to assist in the process and formulation design (Li et al., 2004:77). Chitin is the second most abundant naturally occurring biopolymer after cellulose (Asada et al., 2004: 169). Chitosan is produced by the partial alkaline N-deacetylation of chitin (Berger et al., 2004:36). The structure of chitosan is similar to that of cellulose, an excipient with acceptable compression properties. According to Olsson and Nystrom (2001 :204) hydrogen bonds are considered to be one of the dominating bonding mechanisms for most pharmaceutical powders. The extent of the effect will depend on the particle shape and surface characteristics (Hiestand, 1997:237-241). Considering the structure of chitosan it predicts the ability to form H-bonds, and produce tablets with acceptable mechanical strength. The two major problems identified in terms of the use of chitosan as directly compressible filler in tablet formulations is its poor flow and compressibility properties (Aucamp, 2004; Buys, 2006; De Kock, 2005). During the characterization of chitosan raw material the aim was to determine to which extend its physical properties affects the flow of the material and to compare its flow properties to that of other commonly used tablet fillers. Two batches chitosan were compared to each other to determine the effect of morphology on their physical properties. When ranking the composite index of the powders it was clear that in regards to the other materials used, chitosan was ranked the lowest. These results confirmed the poor flow of chitosan. The characterization of the two chitosan batches used in this study revealed significant differences in the morphology of the particles of the different batches. Because of these large inter-batch variations with respect to the physical properties of the different batches even when manufactured by the same company via the same method, these variations also affected the flow characteristics of the two batches. From the particle characterization in chitosan it could be concluded that the previously observed poor compression characteristics (De Kock, 2005; Aucamp, 2004) could be attributed to the low density and high porosity of the material. Only one of the batches studied could be compressed on a standard eccentric press, which could be attributed to the differences between the physical properties of two batches. Chitosan showed promising compression characteristics at specific machine settings (limited range of upper punch settings), with good crushing strength and low friabifity. The drawbacks of the compression properties for chitosan on the standard press was the relative low tablet weights that could be compressed for a specific die size and the narrow range for the upper punch setting to achieve an acceptable mechanical tablet strength and friability. The results of Buys (2006) showed promising results for chitosan when changing the compression cycle from a single fill to a double die fill for each compression cycle. The advantage of the modified eccentric tablet press in terms of improvement of the compactibility of low density materials was clearly demonstrated by the results from the compression studies of both chitosan batches. With the double fill cycle on the modified press it was possible to fill the die with a sufficient amount of powder to produce acceptable tablets with sufficient crushing strength and low friability. The modified tablet press made it possible to compress the batch (021010) chitosan which couldn't be compressed on the standard tablet press. Batch (030912), which was compressed on the standard as well as the modified press, showed improved results in the crushing strength and friability with increase of the percentage compression setting at a constant upper punch setting. Batch 030912 showed better results than that of batch 021010 and this could be attributed to the physical differences between the two batches. / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2009.

The most useful dosage form taken from a patient's point of view is tablets because of its simplicity and portability (Takeuchi et al., 2004:132). Manufacturing of tablets can be done by wet granulation or direct compression of powders. For direct compression it is important that the powder has good particle flowability and compactability. Various methods to investigate these properties of the powder have been developed, which provide comparative indices to assist in the process and formulation design (Li et al., 2004:77). Chitin is the second most abundant naturally occurring biopolymer after cellulose (Asada et al., 2004: 169). Chitosan is produced by the partial alkaline N-deacetylation of chitin (Berger et al., 2004:36). The structure of chitosan is similar to that of cellulose, an excipient with acceptable compression properties. According to Olsson and Nystrom (2001 :204) hydrogen bonds are considered to be one of the dominating bonding mechanisms for most pharmaceutical powders. The extent of the effect will depend on the particle shape and surface characteristics (Hiestand, 1997:237-241). Considering the structure of chitosan it predicts the ability to form H-bonds, and produce tablets with acceptable mechanical strength. The two major problems identified in terms of the use of chitosan as directly compressible filler in tablet formulations is its poor flow and compressibility properties (Aucamp, 2004; Buys, 2006; De Kock, 2005). During the characterization of chitosan raw material the aim was to determine to which extend its physical properties affects the flow of the material and to compare its flow properties to that of other commonly used tablet fillers. Two batches chitosan were compared to each other to determine the effect of morphology on their physical properties. When ranking the composite index of the powders it was clear that in regards to the other materials used, chitosan was ranked the lowest. These results confirmed the poor flow of chitosan. The characterization of the two chitosan batches used in this study revealed significant differences in the morphology of the particles of the different batches. Because of these large inter-batch variations with respect to the physical properties of the different batches even when manufactured by the same company via the same method, these variations also affected the flow characteristics of the two batches. From the particle characterization in chitosan it could be concluded that the previously observed poor compression characteristics (De Kock, 2005; Aucamp, 2004) could be attributed to the low density and high porosity of the material. Only one of the batches studied could be compressed on a standard eccentric press, which could be attributed to the differences between the physical properties of two batches. Chitosan showed promising compression characteristics at specific machine settings (limited range of upper punch settings), with good crushing strength and low friabifity. The drawbacks of the compression properties for chitosan on the standard press was the relative low tablet weights that could be compressed for a specific die size and the narrow range for the upper punch setting to achieve an acceptable mechanical tablet strength and friability. The results of Buys (2006) showed promising results for chitosan when changing the compression cycle from a single fill to a double die fill for each compression cycle. The advantage of the modified eccentric tablet press in terms of improvement of the compactibility of low density materials was clearly demonstrated by the results from the compression studies of both chitosan batches. With the double fill cycle on the modified press it was possible to fill the die with a sufficient amount of powder to produce acceptable tablets with sufficient crushing strength and low friability. The modified tablet press made it possible to compress the batch (021010) chitosan which couldn't be compressed on the standard tablet press. Batch (030912), which was compressed on the standard as well as the modified press, showed improved results in the crushing strength and friability with increase of the percentage compression setting at a constant upper punch setting. Batch 030912 showed better results than that of batch 021010 and this could be attributed to the physical differences between the two batches. / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2009.

Spherical agglomerates of benzoic acid crystals have been successfully prepared by drowning-out crystallization in three solvent partial miscible mixtures. Benzoic acid is dissolved in ethanol, bridging liquid is added and this mixture is fed to the agitated crystallizer containing water as the anti-solvent. Small crystals are produced by crystallization of the substance, and the crystals are agglomerated through the action of the bridging liquid. Different solvents: chloroform, toluene, heptane, pentane, cyclohexane, ethyl acetate and diethyl ether are chosen as bridging liquids, all being low soluble in water and showing good wettability for benzoic acid crystals. The influence of process conditions such as concentration of solute, agitation rate, feeding rate, amount of bridging liquid and temperature on the properties of benzoic acid spherical agglomerates, are investigated. Different sets of experiments were accomplished to track how the properties of the particles gradually change during the normal spherical crystallization experiment. Other sets of experiments were performed to examine the influence of agitation and process time for agglomeration. The product properties such as particle size distribution, morphology and mechanical strength have been evaluated. The mechanical strength of single agglomerates has been determined by compression in a materials testing machine, using a 10 N load cell. Compression characteristics for single agglomerates are compared with the data on bed compression. The present study shows that the bridging liquid has significant influence on the product properties, using diethyl ether and ethyl acetate no agglomerates are formed. Using any of the other five solvents (chloroform, toluene, heptane, pentane, and cyclohexane) spherical agglomerates are formed, as long as a sufficient amount of the bridging liquid is used. Using cyclohexane as bridging liquid at 5°C and toluene at 20°C the particles are larger compared to particles formed at other conditions. The highest particle fracture stress is obtained by using toluene as the bridging liquid at 5 and 20°C. Particle morphology depends on the bridging liquid used and the particles are completely spherical when toluene and pentane are used as bridging liquids. Different process parameters are found to have a significant influence on the physico-mechanical properties of the product. The range of operation for spherical agglomeration is relatively narrow and only at certain conditions spherical agglomerates are produced. With increasing amount of bridging liquid the particle size and strength increase and the morphology improves. Particle size decreases and the fracture force increases with increasing feeding rate, but the morphology remains unchanged. For all the solvents, the particle size and the fracture stress increase with decreasing temperature. For four of the solvents the morphology improves with decreasing temperature. For cyclohexane the result is the opposite, in that the particles are spherical at 20°C and irregular at 5°C. Spherical agglomerates of benzoic acid, both as single particles as well as in the form of a bed, have a high compressibility and low elastic recovery, properties that are favorable for direct tabletting. As the feed solution is supplied to the crystallizer the amount of benzoic acid that can crystallize actually does crystallize fairly rapidly. Hydrodynamics are responsible for bringing particles together for the agglomeration. Experiments reveal that during the gradual addition of the feed to the agitated aqueous solution, both particle size and particle number increases. It is clear from the experiments that not only further addition of feed solution leads to larger product particles but also continued agitation. Along the course of the process the properties of the particles change gradually but substantially. By continued agitation, the particle porosity decreases, density, strength gradually increases and also the spherical shape develops gradually. / QC 20110419

Several researchers have concluded that there is little or no relationship between specific gravity and ring width or growth rate in yellow-poplar (Liriodendron tulipifera L.). Because most mechanical properties of wood are also closely related to specific gravity, it would thus be of interest to learn how minimum suppression and maximum release years' evidence that can be extracted from radial growth patterns based on a modified radial growth averaging (RGA) technique's influence the compression parallel to grain strength and specific gravity of wood. This study is designed to evaluate the effects of growth suppression and release on ultimate crushing stress and specific gravity for small-sized yellow-poplar specimens. Additionally, the relationship between specific gravity and ultimate crushing stress is investigated. Twenty-three yellow-poplar cores were examined for their growth ring widths. Minimum suppression and maximum release years were identified based on the modified RGA criteria method. From each increment core, three 1 Ã 1 Ã 4 mm specimens from both minimum suppression and maximum release years were tested for their ultimate crushing stresses using a micro-mechanical test system. The specific gravity of each specimen was also recorded. These data were analyzed using a paired samples t test and a simple linear regression. The results indicate that the mean ultimate crushing stress and specific gravity of maximum release years were significantly higher than that of minimum suppression years. Furthermore, the ultimate crushing stress was linearly related to the specific gravity of the specimens. / Master of Science

La présente étude porte sur le comportement mécanique de deux types de supports de catalyseurs utilisés industriellement en hydrotraitement des résidus. Ces supports extrudés, fabriqués par IFPEN, sont constitués d’alumine de transition γ avec un taux de porosité proche de 70%. La porosité du premier matériau est uniquement constituée de mésopores (< 50 nm). La porosité du second matériau est constituée de mésopores et de macropores (jusqu’à 20 µm). Les niveaux de sollicitation en service étant très peu connus, cette étude s’attache à décrire de manière précise et exhaustive le comportement mécanique de ces supports sous une large gamme de sollicitations, et à identifier les différents mécanismes de ruine possibles. L’objectif final est de mieux comprendre les relations entre les paramètres microstructuraux et les propriétés mécaniques afin d’identifier des leviers d’amélioration de la tenue mécanique des supports. Dans un premier temps, une méthodologie adaptée de caractérisation mécanique est établie. Le comportement des supports est étudié d’une part en traction, à l’aide d’essais de flexion trois points et d’écrasement diamétral, et d’autre part, en compression sous différents taux de triaxialité, à l’aide d’essais de compression uniaxiale et hydrostatique et d’essais de micro-indentation sphérique. Les différents mécanismes responsables de la ruine des supports sont identifiés au moyen de techniques d’imagerie telles que la microscopie électronique à balayage et la micro-tomographie à rayons X. En traction, le comportement est fragile avec l’amorçage de la rupture sur un défaut critique. En compression, une transition fragile / quasi-plastique du comportement est observée avec l’augmentation du taux de confinement. Cette quasi-plasticité s’exprime en particulier à travers un phénomène de densification de la macroporosité. Dans un deuxième temps, un critère de rupture est identifié pour chaque type de matériau en vue de représenter sur une même surface de charge les différents types de comportement et phénomènes physiques observés. Cette identification est réalisée en couplant les essais d’indentation sphérique à une analyse numérique. Des critères faisant intervenir la pression hydrostatique permettent de rendre compte de la forte dissymétrie du comportement des matériaux en traction et en compression. Enfin, dans un souci de se rapprocher des sollicitations subies par les supports de catalyseurs dans un réacteur en service, le comportement d’un empilement de supports est étudié en compression œdométrique. L’analyse de cet essai par tomographie à rayons X permet de déterminer les différents mécanismes de ruine intervenant au sein d’un empilement, en particulier ceux responsables de la génération de fines. Les résultats illustrent la pertinence de la caractérisation en flexion et en indentation des supports de catalyseurs seuls pour prévoir leur comportement au sein d’un empilement en compression. / In this work, we study the mechanical behaviour of two types of catalysts supports produced by IFPEN and industrially used in residues hydrotreating. Those extruded supports are made of transition γ-alumina with about 70% of porous volume. The first material’s porosity is exclusively composed of mesopores (< 50 nm). The porosity of the second material is composed of both mesopores and macropores (up to 20 µm). Because of the limited knowledge of the stress fields in embedded catalysts supports in use in a reactor, this study aims at precisely and exhaustively describing the mechanical behaviour of those supports under a wide range of stresses, and identifying the possible damage mechanisms. The final objective is to better understand the influence of microstructural parameters on the mechanical properties of the supports in order to propose some leads about how to improve their mechanical strength. First, an adequate mechanical characterization methodology is set. On one hand, the tensile mechanical behaviour of the supports is studied with three-point bending and diametrical crushing tests. On the other hand, their compressive behaviour under various triaxiality rates is characterized in uniaxial and hydrostatic compression, and by spherical micro-indentation. The different damaging mechanisms are identified by imaging techniques such as scanning electronic microscopy and X-ray micro-tomography. Under tensile stresses, the supports exhibit a brittle behaviour and fracture initiates at a critical flaw. Under compressive stresses, a brittle/quasi-plastic transition is observed with increasing the triaxiality rate. The quasi-plasticity is mainly due to the densification of the macroporosity. The second part of the study consists in identifying, for each material, a fracture criterion able to represent every types of behaviour and physical phenomena observed on the same yield surface. This identification is achieved by coupling the spherical indentation tests to a numerical analysis. Fracture criteria involving hydrostatic pressure are well suited to describe the highly dissymmetric mechanical behaviour of the materials in tension and in compression. The last part of this work aims at studying the mechanical behaviour of a stack of supports under œdometric compression in order to produce stress fields more representative of those existing within the supports stacked in a reactor. This test is analysed by X-ray tomography, which allows us to determine/acknowledge the different damaging mechanisms involved in fragments and fines generation. The results illustrate the suitability of the bending and indentation tests to characterize the mechanical properties of a single support and relate them to its mechanical behaviour in a stack of supports under compression.