The internal dynamics of powder systems under compression are as of yet not fully understood, and thus there is a necessity for approaches that can help in further clarifying and enhancing the level of understanding on this subject. To this end, the internal dynamics of powder systems under compression were probed by means of force distributions and a novel compaction equation. The determination of force distributions hinged on the use of carbon paper as a force sensor, where the imprints transferred from it onto white paper where converted through calibration into forces. Through analysis of these imprints, it was found that the absence of friction and bonding capacity between the particles composing the powder bed had no effect on how the applied load was transferred through the system. Additionally, it was found that pellet strength had a role to play in the homogeneity of force distributions, where, upon the occurrence of fracture, force distributions became less homogenous. A novel compaction equation was derived and tested on a series of systems composed of pellets with differing mechanical properties. The main value of the equation lay in its ability to predict compression behavior from single particle properties, and the agreement was especially good when a compact of zero porosity was formed. The utility of the equation was tested in two further studies, using a series of pharmaceutically relevant powder materials. It was established that the A parameter of the equation was a measure of the deformability of the powder material, much like the Heckel 1/K parameter, and can be used as a means to rank powders according to deformability, i.e. to establish plasticity scale. The equation also provided insights into the dominating compression mechanisms through an invariance that could be exploited to determine the point, at which the powder system became constrained, i.e. the end of rearrangement. Additionally, the robustness of the equation was demonstrated through fruitful analysis of a set of diverse materials. In summary, this thesis has provided insights and tools that can be translated into more efficient development and manufacturing of medicines in the form of tablets.

1 Abstract Charles University in Prague, Faculty of Pharmacy in Hradci Králové Department of: Departmanet of Pharmaceutical technology Consultant: doc. PharmDr. Zdeňka Šklubalová Ph.D. Student: Hana Machutková Title of Thesis: Influence of different types and ratios of microcrystalline cellulose and lactose on physical properties of tablet blends and tablets. In this study, the properties of tablet blends prepared from five different kinds of microcrystalline cellulose (Avicel ® A-101, 102, 105, 112, 200) and three types of lactose in different proportions were evaluated. Moisture content, the bulk and tapped density and the angle of repose were compared for tablet blends. The addition of lactose to the mixtures caused the decrease in the moisture content in the tablet blends. After evaluating the flow properties, the mixtures with suitable characteristics were compacted at compression forces of 8 and 12 kN. The force required to eject the tablet, the table strength, the disintegration time and the friability of the resulting tablets were estimated. The worst compressibility was identified for mixtures with higher concentration of Avicel 105. Due to its very small and fine particles (approximately 20μm) the filling of matrix was not uniform making tablet compression unsuccessful and thus the of uniform...

Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of: Pharmaceutical technology Consultant: Mgr. Petra Svačinová, PhD. Student: Le Thanh Tra Title of Thesis: Evaluation of stress relaxation of mixtures of lactosum and calcii hydrogenphosphate for preparation tablets with theophylline This thesis studies viscoelastic behavior of fillers and tensile strength of tablets with theophylline. Used material are described in theoretical part: Laktosum SpheroLac 100, microcrystalline cellulose Comprecel 102, calcium hydrogenophosphate anhydrate Di-Cafos A150, calcium hydrogenophosphate dihydrate Di-Cafos D160, theophylline and magnesium stearate. Thesis also describes the stress relaxation test, methods of evaluation and it's application. Experimental part evaluates viscoelastic behavior and tensile strength through the test of stress relaxation with maximal compression force 10 kN and dwell time 180 s. The tensile strength of tablets is also evaluated. Experimental part evaluates parameters of elasticity Ai and plasticity Pi, which were obtained from the test of stress relaxation. It evaluates effect of different fillers on these parameters. The highest values were measured at mixtures E (Spherolac 100 a Comprecel 102), further at mixtures D (Spherolac 100 a Di-Cafos A150) and...

Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of: Pharmaceutical technology Consultant: Doc. PharmDr. Zdeňka Šklubalová, Ph.D. Student: Ondřej Damborský Title of Thesis: Flow equation of sorbitol granules with addition of magnesium stearate. The aim of this thesis is to study particulate built and consolidation properties of the granulate prepared by wet granulation of sorbitol and it's size fractions in the range of 0,2 - 0,8 mm and it's influence of adding lubricate magnesium stearate 0.5% and 1.0%. The properties were studied by the angle of repose, the three kinds of bulk density, tap density, the Hausner ratio. The granules showed adequate to good flow properties. The addition of magnesium stearate flow increases the rate through the granulate sorbitol. Mass flow rate through the orifice the conical hopper of the test depending on the particle size and hole diameter were monitored. With increasing particle size the rate of pouring decreases, while the diameter of the hole had the opposite effect. Dependence of the flow rate to the average of the opening of the hopper was modeled by a power equation Jones-Pilpel. When using the current parameters with accuracy reverse estimate of the flow rate ranged between approximately 2 - 4%.

Charles University in Prague, Faculty of Pharmacy in Hradci Králové Department of Pharmaceutical Technology Consultant: Mgr. Pavel Ondrejček, Ph.D. Student: Tomáš Marcinek Title of Thesis: The influence of the tableting speed on the compaction process The main aim of this thesis was to determine the influence of tableting speed on the compaction process of four substances. The compaction process was evaluated by three- exponential equation. The parameters of this equation describe the individual phases of compression, the precompression phase, the phase of elastic deformation and the phase of plastic deformation. Furthermore, the effect of tableting speed on the compressibility of the material was studied using the force-displacement record. Finally, the influence of tableting speed on tensile strength of the prepared tablets was evaluated. Four materials were used for the evaluation. Microcrystalline cellulose Avicel PH-102 and dicalcium phosphate dihydrate DI-CAFOS were used as model fillers. Theophylline and paracetamol were used as model drugs. The course of the compaction process was evaluated at five compaction speeds. The results of this evaluation revealed different behavior of used materials. Furthermore different influence on the compaction process by changing compaction speed was...

Charles University in Prague, Faculty of Pharmacy in Hradci Králové Department of: Department of Pharmaceutical Technology Consultant: Mgr. Pavel Ondrejček, Ph.D. Student: Nikola Marcinková Title of Thesis: The influence of the die size on the compaction process This diploma thesis is focused on exploration the influence of the die size on the compaction process. That was evaluated by parameters of three-exponential equation. Compressibility was studied by using force-displacement record. In this work was also observed an effect of die size on the tensile strength. In processing the experimental part of this work were used four different model materials. Microcrystalline cellulose and dicalcium phosphate are used as model fillers and theophylline and paracetamol as model active substances. Compaction of these materials was carried out in dies of size 7 mm, 9 mm, 11 mm, 13 mm and 15 mm. The results of the work showed that the die size significantly affects all parameters force-displacement record. With the growing size of the die there was a reduction of energy parameters. Most of the compaction parameters were statistically influenced. Increasing die size caused reducing volume reduction and energy consumption and increased speed of volume reduction at the stage of pre- compression and elastic...

Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Technology Consultant: Mgr. Pavel Ondrejček, Ph.D. Student: Simona Berková Title of Thesis: The evaluation of compressibility of the mixtures pellets and microcrystalline cellulose This thesis is focused on the evaluation of powdered microcrystalline cellulose, pellets and mixtures thereof. Comprecel 102 was used as powdered microcrystalline cellulose. The used pellets were commercially available pellets Cellets 100 made of microcrystalline cellulose. The flow properties of used materials and their mixtures were evaluated by using the angle of repose, flow through orifice and Hausner ratio methods. Further the compressibility was evaluated using the force-displacement record. For the evaluation of compaction proces the three exponential compaction was used. Finally the radial tablet strength and tablet friability was tested. The results showed, that the flow properties improved with an increasing amount of pellets in mixture. I tis due to higher bulk and tapped density and also narrower particle size distribution, smoother surface and the regular shape of used pellets. The parameters of the force-displacement method showed different compressibility of used tabletting mixtures. The evaluation of...

Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of: Pharmaceutical technology Consultant: Mgr. Petra Svačinová, Ph.D. Student: Michaela Přeučilová Title of Thesis: A comparison of viscoelastic properties of mixtures of lactose and different lubricants using the stress relaxation test This diploma thesis deals with viscoelastic properties of pharmaceutical excipients and tensile strength of tablets made of these excipients. Theoretical part is dedicated to description of lactose and lubricants, further the tablets compressibility and compression energy profile are described. The end of theoretical part deals with the stress relaxation test, with evaluation methods and the stress relaxation test influence on lactose tablets with different types of lubricants as well. The experimental part deals with the evaluation of the viscoelastic properties of two types of lactose and their mixtures with different types of lubricants at concentration of 1%. These characteristics were evaluated by stress relaxation test. All tablets were compressed by compression forces of 13 kN and 15 kN with dwell time 180 seconds. The study was about differences between two types of lactose, effect of lubricants and effect of two different compression forces on parameters of elasticity A1 -A3 and...

Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of: Pharmaceutical technology Consultant: Mgr. Petra Svačinová, Ph.D. Student: Straková Markéta Title of Thesis: The influence of dwell time on the parameters of the stress relaxation test for lactose and calcium hydrogen phosphate The aim of this thesis is to find out viscoelastic properties of pharmaceutical excipients and to evaluate the tensile strength of tablets made of them. The theoretical part describes used materials, these are lactose, calcium hydrogen phosphate and magnesium stearate. The thesis also deals with the stress relaxation test, its evaluation and usage. Tensile strength, calculation and various factors that affect tensile strength are described in the text. The experimental part deals with viscoelastic properties of used materials and their mixtures with lubricant using the stress relaxation test. Different dwell times (60 s, 120 s, 180 s, 240 s, 300 s, 360 s, 420 s, 480 s, 540 s, 600 s) were used for individual measurements. The relation between elasticity parameters (A1, A2, A3) and plasticity parameters (P1, P2, P3) depending on the dwell time was investigated. As for calcium hydrogen phosphate, the dwell time 180 - 240 seconds was found as the most appropriate. As for lactose, the optimum dwell...

Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Technology Consultant: Mgr. Pavel Ondrejček, Ph.D. Student: Žofie Trpělková Title: A study of a compaction process of microcrystalline cellulose pellets This work is aimed at the comparison of two types of microcrystalline cellulose (Comprecel 102 a Avicel PH-200) with two types of pellets made of microcrystalline cellulose (Cellets 100 a Cellets 200). Important properties for the compaction into tablets were analyzed in these materials. The particle size distribution, the content of moisture, the bulk and tapped density, the flowability, the angle of repose and the Hausner ratio were evaluated. Furthermore, the compaction process was described by using the force displacement method and the three-exponential equation. Finally, the radial strength and the friability of tablets prepared by using two different compaction forces were evaluated. The results proved that both types of pellets have much better flow properties than powdered microcrystalline celluloses. This is primarily caused by the narrow particle size distribution, higher bulk and tapped density and the significantly smoother surface of pellets. Better flow properties of the pellets also influenced the parameters of the force-displacement...