Active pharmaceutical ingredients (APIs) are frequently delivered to the patient in the solid-state as part of an approved dosage form (tablets, capsules, etc.). Understanding and controlling the solid-state chemistry of APIs is therefore an important aspect of the drug development process. APIs can exist in a variety of distinct solid forms, including polymorphs, solvates, hydrates, co-crystals and amorphous solids. Each form displays unique physicochemical properties that can profoundly influence the bioavailability, manufacturability, stability and other performance characteristics of the drug. Most APIs are purified and isolated by crystallisation from an appropriate solvent during the final step in synthetic process. The main objective of a crystallisation process is to produce crystals with desired properties such as particle size distribution (PSD), shape and purity. All pharmaceutical dosage forms must be produced in uniform units, and good content of uniformity is only possible when the size of the active component is carefully controlled. For on-line control of crystallisations of Quetiapine Fumarate to achieve desired PSD and no changed physicochemical purity was used the Lasentec Focus Beam Reflectance Measurement (FBRM) system.

1 Abstract Charles University in Prague, Faculty of Pharmacy in Hradci Králové Department of: Pharmaceutical technology Consultant: PharmDr. Ondřej Holas, Ph.D. Student: Tomáš Máčalík Title of Thesis: Problematics of active compounds recrystalisation in pharmaceutical preparations The topic of the thesis is the recrystallization of active substances in pharmaceutical preparations. The aim of this work is to demonstrate this phenomenon on a real particular pharmaceutical product, in which it has occurred. It includes a detailed description of the manufacturing process including all mandatory conditions, possible critical points, investigations and measures taken. The thesis consists of two parts. The first describes in details the current state of knowledge. It is based on the findings of the available literature on the subject. The basic concepts of crystallization and polymorphism are explained in detail, which form the basis for the subsequent case study. The case study includes a detailed description of a specific medicinal product. Subsequently, it's production, good manufacturing practice and gradual investigation of the discovered technological incompatibility are explained step by step. The result of the work points out that the issue of recrystallization and polymorphism is very closely related to...

Texture of igneous rocks, which includes size, shape and spatial distribution of grains, represents the final record of kinetic and mechanical processes operating during ascent and final emplacement of a magma. However, traditional geochemical approaches cannot assess and verify the physical processes of magma solidification, in particular, crystal nucleation and growth, textural coarsening, or mechanical crystal-melt interactions. In this work, I apply stereological methods to quantitatively characterize the textures and to interpret the crystallization history of granitic rocks in the Western Krušné hory/Erzgebirge and Vogtland. The Western Krušné hory/Erzgebirge granites consist of three suites: biotite granites (Kirchberg), muscovite-biotite microgranites (Walfischkopf), and topaz-zinnwaldite alkali- feldspar granites (Eibenstock), which consist of eight intrusive units and two aplite dyke sets. The entire granite sequence exhibits an extreme and nearly continuous differentiation range, but in detail the evolutionary trends of each suite are independent, and individual intrusive units are also clearly compositionally separated. The granites consist of 29-43 vol.% quartz, 20-30 vol. % plagioclase, 22-31 vol. % K-feldspar, 2-9 vol. % biotite, <2 vol. % muscovite, and minor topaz and apatite. All...

The aim of the thesis was to compare the haloalkane dehalogenase DhaA106 with other studied protein mutant variants. For diffraction analysis, it was necessary to growappropriate crystals of DhaA106 protein. Crystallization experiments were performed by standard sitting drop method. Obtained rod crystals were used for diffraction analysis. During diffraction measurement completeset of 500 diffraction images were obtained, from which the electron density map was formed and the spatial model of the molecular structure of DhaA106 dehalogenase was created. Alternative conformation of amino acids, water molecules, parts of precipitating solution and chloride ion inthe active sitewere subsequently added into the model structure. The final structure of the moleculewas refined and validated. Subsequently, the amino acids pentade in the active site and whole protein structure were analyzed . Values of validation and refining and interatomic distances in the active site were compared with several variants mutant dehalogenase DhaA, as well as the precipitating solutions used for crystallization and diffraction data collection. In the last step of the work interactions of the selected substrate with the protein surface in the vicinity of the tunnel connecting the active site of the surfacewere studied. Mentioned interaction study was based on the principle of combination of the Monte-Carlo methods with protein structure prediction algorithms.

Crystallisation of epoxy resins based on bisphenol A and bisphenol F is the natural property of these oligomers. However, manufacturers of paints and other systems based on these epoxy resins, strive to slow down the crystallisation process as much as possible, thereby prolonging the shelf life and improving the competitiveness of their products. The main aim of the thesis is generalisation of the factors influencing the crystallisation process of epoxy resins based on bisphenol A and bisphenol F, verifying new approaches to the possibility of influencing the crystallisation process and determining the possibility of using a certain degree of epoxy resins crystallinity based on bisphenol A and bisphenol F in the preparation and production of epoxy resinbased coating systems.

Růst krystalů zásadně ovlivňuje morfologii a tím také mechanické vlastnosti semikrystalických polymerů. Tato PhD práce přináší alternativní pohled na popis kinetiky krystalizace v polyolefinech plněných slabě interagujícími částicemi. V nanokompozitních materiálech vysoký specifický povrch plniva i při nízkých plněních zásadně ovlivňuje dynamiku řetězců. V blízkosti povrchu plniva začíná hrát významnou roli zpomalená reptace způsobená jak vzájemnými interakcemi plnivo-polymer tak prostorovým omezením mezi nanočásticemi. Růst krystalů byl zkoumán pomocí polarizovaného optického mikroskopu vybaveného horkým stolkem. Výsledky byly korelovány s teoretickými modely a rozsáhlými počítačovými simulacemi na molekulární úrovni. Pozorovaný pokles rychlosti růstu sférolitů v závislosti na obsahu plniva a molekulové hmotnosti matrice je interpretován na základě imobilizační teorie, tedy, zpomalení reptačního pohybu.

This diploma thesis deals with crystallization additives used to modify cement composites. Describes their principle of operation, application methods and also mentions the different manufacturers with their products. In this work were made test samples with Xypex Admix crystallization additive which were tested for mechanical and physical properties depending on the amount of crystallization additives, aggressive environment and the duration of exposure in this environment. Selected samples were analyzed with RTG, DTA, SEM and porosimetry for detailed examination of the microstructure.

Mafic and intermediate intrusions commonly accompany Variscan granitoid plutons in Europe. They are documented from different localities of Iberian Peninsula, from the French Massif Central, Schwarzwald, from different parts of the Bohemian Massif, in Romania, Greece, Corsica and Sardinia. They comprise wide petrographic varieties from quartz gabbros, diorites, granodiorites to monzonites. They usually constitute small bodies or veins, they often occur as mafic microgranular enclaves (MME) in granodiorites and in some granites. Dioritic intrusions are characterized by a relatively high amounts of lithophile elements (Rb, Sr, Ba, Cs, LREE), and they are simultaneously high in compatible elements (Ni, Cr, V a Co). Their isotopic ratios 87 Sr/86 Sr are in all compared locations similar and are close to the Bulk Earth (0.704 - 0.708). εNd values show larger scatter, some intrusions have more crustal composition (to -8), on the other hand, another intrusions have εNd positive, that points to a contribution of basic magma. The age of dioritic intrusions differs according to individual locality suggesting more than one magmatic episode. The oldest occur in the French Massif Central (361 - 365 Ma), whereas the youngest are documented in Iberia (312 - 310 Ma). The oldest mafic intrusions in the Bohemian...

The work deals with the development of new types of gas and waterproof tight coatings based on secondary crystallization of cement, using industrial waste as secondary raw material in the formulation of new recipes.

The work deals with the preparation and study of polyphosphate composites. Aluminum phosphates provide some unusual properties like high-heat resistance in terms of inorganic binders. The addition of chromium in the form of Cr2O3 or directly the bond with the aluminum-chromium-phosphate can improve the properties of this binder. Highly viscous Al2Cr(H2PO4)9 and Al3Cr(H2PO4)12 binders were prepared by dissolving Al(OH)3 and CrO3 in 85% phosphoric acid, and mixed with Al2O3 and Cr2O3 fillers. The composites were cured in the furnace at 150 °C for 24 h under pressure of 10 MPa. During the annealing at temperatures up to 1 500 °C changes in chemical structure of the cured composites were observed, leading to the understanding of the creation of crystalline phases and their eventual changes. The characterization of binders was mainly based on FT-IR, EDAX, TG-DTA and optical microscopy analyses.