1 Abstract Charles University in Prague, Faculty of Pharmacy in Hradci Králové Department of: Pharmaceutical Technology Consultant: Doc. PharmDr. Zdeňka Šklubalová, Ph.D. Student: Barbora Jonášová Title of Thesis: Flow equation. Sorbitol and magnesium stearate. This thesis describes influence of the addition of magnesium stearate on bulk properties to size fractions of sorbitol for direct compression in the range 0,100 - 0,346 mm. I studied influence of particle size and the size of the opening hopper to the gravitational speed of flow. The dependence of the flow rate (g/s) on the size of the opening conical hopper was modeled by the squares equation Jones-Pilpel. No significant effect of addition of magnesium stearate 0,5% and 1,0% for the exponent equation was found. This model allows the re-estimation of the flow rate with an accuracy about 11% for the size fraction regardless of the amount of added magnesium stearate; for polydisperse MS200 is the deviation of the experimentally determined values of the flow rate of approximately 19%.

Charles University in Prague, Faculty of Pharmacy in Hradci Králové Department of: Pharmaceutical technology Consultant: doc.PharmDr.Zdeňka Šklubalová, Ph.D Student: Hana Čermáková Title of Thesis: Flow equation. Sorbitol In this diploma thesis, the granulometric, bulk and consolidation properties of sorbitol for direct compression are studied. The effect of particle size on bulk and tapped density, angle sprinkles and the flow rate through the model conical hopper with a different orifice diameter are examined. The relationship of the flow rate (g/s) of particle size fractions on the orifice diameter is modelled by the Jones-Pilpel equation with the accuracy of the flow rate prediction approximately 10 %.

Charles University, Faculty of Pharmacy in Hradec Králové Department of: Department of Pharmaceutical Technology Consultant: doc. PharmDr. Zdeňka Šklubalová, Ph.D Student: Kristýna Kýhosová Title of Thesis: Study of flow and consolidation behaviour of lactose This diploma thesis studies flow and consolidation behaviour of three types of lactose, which differed in the methode of manufacture (crystalization, milling, spray drying). Particle size distribution was characterized by the sieve analysis. The bulk and tapped density, the angle of repose, the flow rate through an orifice of the hopper and true density measured by helium pycnometer were evaluated. The volume changes of powder bed and porosity during consolidation in the relationship on gravitational tapping were studied. To describe the consolidation process, the exponentional mathematical model was used, which made possible to calculate N1/2, that shows the number of taps needed to reach one half of the powder volume reduction. The values noted for lactose were in the range of 3-5.8.

7 2 Abstract Charles University in Prague, Faculty of Pharmacy in Hradci Králové Department of: Pharmaceutical Technology Consultant: doc. PharmDr. Zdeňka Šklubalová, Ph.D. Student: Alexandra Šofranková Title of Thesis: Fractal aspects of flow and consolidation behaviour of microcrystalline cellulose The object of this diploma thesis was to study the flow and consolidation characteristics of three types of microcrystalline cellulose. The granulometric characteristics, including the linear fractal dimension, were estimated using the optical microscopy. The bulk and tapped density, the angle of repose and the flow rate through an orifice of the hopper were evaluated. True density of the materials and the porosity of a loose powder bed were determined by helium pyknometry. The changes of density by the gravity consolidation were studied; the relationship of Hausner ratio on the number of taps describes best the differences in the consolidation behaviour of the substances. Modelling the consolidation kinetic by the exponential law allowed to determine the parameter N1/2, which shows the number of taps needed to reach one half of the powder volume reduction. The values of N1/2 within a range of 6,9-18 correlated well with the particle size of the used types of microcrystalline cellulose.

Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of: Pharmaceutical Technology Consultant: doc. PharmDr. Zdeňka Šklubalová, Ph.D. Student: Michaela Bérešová Title of Thesis: Study of consolidation behaviour of lactose and its blends Flow behaviour and consolidation properties are important characteristics of the powder substances. The aim of this thesis was to evaluate these properties for four types of lactose with different particle size and for the mixtures of two lactoses with different flow properties. The density and porosity of the powder bed and their changes during the consolidation due to the gravitational tapping were studied. The non-linear regression equation was used to describe the consolidation process for the samples and the parameter N½, which expresses the number of taps needed to achieve a half reduction of a powder bed volume. The value of N½ increased with the decrease in the particle size.

Charles University, Faculty of Pharmacy in Hradec Králové Department of: Pharmaceutical technology Supervisor: doc. PharmDr. Zdeňka Šklubalová, Ph.D. Consultant: Ing. Hana Hurychová Student: Eliška Dostálová Title of Thesis: Study of bulk and consolidation properties of size fractions of anhydrous lactose The bulk and consolidation behaviour of pharmaceutical excipients belong to their important properties. Properties of five size fractions of anhydrous lactose having the particle size in the range of 1-400 µm were studied in this thesis. The measurement was carried out by using static and dynamic pharmacopoeial methods. The bulk density and the tapped density, the angle of repose were evaluated as well as the true density of particles by using the gas pycnometry. The mass flow rate through the orifice of a model conical hopper by the force of gravity was estimated for the individual size fractions. The discharge rate through the orifice having the diameter in a range of 0.6-1.5 cm was modelled with the Beverloo et al and Jones & Pilpel power regression equations; the precision of the flow rate prediction was about 3 %. The best bulk properties were detected for the particle size fraction 246 µm. The results of the evaluation of the consolidation dynamic during the tapping of powder bed permitted...

Králové doc. PharmDr. Zdeňka Šklubalová, Ph.D. Ing. Hana Hurychová, Ph.D. Monika Hnatková The objective of this diploma thesis was to evaluate the flow and consolidation behaviour of the size fractions of lactose for direct compression - Tabletose® 80 in a range of 80-400 μm obtained by sieving. The nonlinear influence of the particle size on the flow rate was detected; the fractions of Tablettose® 80 with the mean size of 245 and 346 µm showed the best flowability. The influence of the diameter of the hopper opening on the flow rate was modeled using the Beverloo and/or Jones & Pilpel flow equation; the latter described the results better. The assessment of volume changes by gravitational tapping allowed to observe dynamics of consolidation and to express porosity factor for the powder bed, which enabled an estimation of the angle of internal friction.

1 Abstract Charles University, Faculty of Pharmacy in Hradci Králové Department of: Department of Pharmaceutical Technology Supervisor: Doc. PharmDr. Zdeňka Šklubalová, Ph. D. Consultant PharmDr. Karel Palát, CSc., Mgr. Žofie Trpělková Student: Martina Litošová Title of Thesis: Homogenization of powder blends using a Turbula mixer. In this experimental work, the influencing of the homogeneity of the powder mixture of acetylsalicylic acid (ASA) and microcrystalline cellulose (Avicel PH102) due to the rotational speed of the mixing container in a range of 23−101 rpm, and the mixing time was studied using the Turbula shaker mixer. Within time interval 2-62 minutes, the content of ASA in samples was measured by near-infrared spectrometry. The expression of standard deviation was used to evaluate the homogeneity of samples. The best results were detected at a rotational speed of 34 rpm within time interval of 14−30 min.

Charles University, Faculty of Pharmacy in Hradci Králové Department of: Pharmaceutical technology Supervisor: doc. PharmDr. Zdeňka Šklubalová, Ph.D. Consultant: Mgr. Žofie Trpělková Student: Aneta Mrázková Title of Thesis: The study of influence of the measurement method on static angle of repose of free-flowable excipients. Good flow and consolidation properties of powders represent significant characteristics of pharmaceutical excipients They are important for manufacturing of powders into solid dosage forms. Flow behavior of 6 free flowing excipients was evaluated in this diploma thesis. The main target was a study of the influence of the masurement method and the orifice size of a conical hopper on static angle of repose (AOR). The automatic tester and the prototype for measuring AOR having orifice sizes in a range of 6-15 mm were used for the measurement. A significant difference between the results of these two methods (P <0.01) was observed. The decrease in AOR was detected when increased the orifice diameter, the effect was significant (P <0.01) only in automatic tester for two out of six measured powders. Surprisingly, the significant influence of the orifice size on AOR was registered for a sweetener Palatinose with protype equipment.

Charles University, Faculty of Pharmacy in Hradci Králové Department of: Supervisor: Pharmaceutical Technology doc. PharmDr. Zdeňka Šklubalová, Ph.D. Consultant: Mgr. Jana Brokešová Student: Daniela Ferechová Title of Thesis: Study of the influence of tablet mixture composition on the flow and consolidation properties Good flow properties of a tabletting mixture play an important role in the manufacturing of tablets. Flow behaviour of the commercial (original) tabletting mixture with poor flowability was evaluated in this thesis. The main aim was to find alternative fillers that may improve its flow. The granulometric characteristics and flowability of eight types of lactose and microcrystalline cellulose and their binary mixtures were studied. In comparison to the original tabletting mixture, the proposed modified one with both original fillers were replaced with new ones showed significantly better flow properties with steady state flow through the hopper orifice having a diameter of 10 mm. The results were confirmed using powder rheometer. The lower shear stress necessary to achieve flow under different normal loads as well as approximately 72 times lower cohesion value were detected for the modified tabletting mixture.