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Spray drying of drug suspension in lactose solution
Vlková, Klára ; Svačinová, Petra (advisor) ; Kováčik, Andrej (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of: Pharmaceutical Technology Consultant: PharmDr. Petra Svačinová, Ph.D. Student: Klára Vlková Title of Thesis: Spray drying of a drug suspension in lactose solution Spray drying can be used to increase the solubility and thus bioavailability of drugs that are poorly soluble in water. In the present work, particles from a suspension of meloxicam in lactose solution were prepared by spray drying. The effect of the nozzle size of 0.7 mm and 1.4 mm, the effect of drug concentration of 0.5 g/100 ml and 1 g/100 ml, and the effect of lactose concentration on the properties of the resulting particles were investigated. The lactose solutions used had concentrations of 15, 20 and 25 %. The appearance and size of the formed particles were evaluated using optical and scanning electron microscopy (SEM). The amount of drug released was investigated using dissolution and the thermal characteristics of the particles were evaluated using differential scanning calorimetry (DSC). The evaluation by SEM and DSC was then performed again 6 months after the first measurement. The resulting particles were spherical in shape with no surface irregularities. Some of them contained clusters of meloxicam particles. At the second observation after 6 months,...
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Effect of mesoporous carrier on the properties of hydrophilic matrix based on hydroxypropyl methylcellulose.
Milá, Jana ; Vraníková, Barbora (advisor) ; Kováčik, Andrej (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of: Pharmaceutical Technology Mentor: doc. PharmDr. Barbora Vraníková, Ph.D. Consultant: Mgr. Chiazor Ugo Ogadah Student: Jana Milá Title of Thesis: Effect of mesoporous carrier on the properties of hydrophilic matrix based on hydroxypropyl methylcellulose Colon targeted drug delivery has an essential role in treating local colon diseases. Various specific drug delivery systems resistant to the acidic environment of the upper gastrointestinal tract are used in the controlled drug release. In addition, higher efficacy, especially of poorly soluble drugs, can also be achieved by using mucoadhesive matrix systems in combination with liquisolid systems. Within these systems, the drug is usually dissolved and, therefore, it does not need to dissolve during release from the dosage form. The aim of the presented work was to study the effect of the mesoporous carrier Neusilin® US2 on the mucoadhesive properties and swelling rate of tablets based on hypromellose. Formulations containing the model drug theophylline, Neusilin® US2, hypromellose K15M (HPMC K15M) or their mixtures were subjected to determination of swelling and mucoadhesion strength in the environment of three biorelevant media simulating the fasted state of the stomach...
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Study of Corneocyte Lipid Envelope
Hrdinová, Iva ; Kováčik, Andrej (advisor) ; Paraskevopoulou, Anna (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Technology Author: Iva Hrdinová Supervisor: doc. PharmDr. Andrej Kováčik, Ph.D. Title of diploma thesis: Study of corneocyte lipid envelope The stratum corneum (SC) is the uppermost layer of the human epidermis. The structure of this layer is composed of corneocytes which are surrounded by a lipid matrix. Besides the free lipids (ceramides, free fatty acids, and cholesterol), there are covalently bound lipids called the corneocyte lipid envelope (CLE). While the role of free lipids is known, the effect of the CLE on the SC permeability is still unclear. In this work, we aimed to answer the question: "Is the CLE important in the skin permeability, and does the CLE play any role as a template for the free lipid arrangement in the SC?" A partial aim of this work was to develop a valid method for the preparation of the CLE models, including SC delipidation/relipidation procedures. We prepared the SC models from the human epidermis. First, we extracted the free lipids from SC with organic solvents, and then we saponified the extracted SC with alkaline methanol. The free lipids were then applied onto the extracted and saponified SC in an organic solvent under different temperature conditions (room temperature vs....
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The human skin barrier model containing stripped stratum corneum
Soukupová, Romana ; Pullmannová, Petra (advisor) ; Kováčik, Andrej (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Biophysics and Physical Chemistry Author: Romana Soukupová Supervisor: Mgr. Petra Pullmanová, Ph.D. Title of diploma thesis: The human skin barrier model containing stripped stratum corneum The uppermost layer of the epidermis, the stratum corneum, acts as a protective skin barrier. It contains a lipid matrix, which is made up of ceramides, cholesterol, and free fatty acids. The composition and arrangement of these lipids are necessary for the proper function of the skin barrier. Corneocytes, which do not have nuclei, are distributed in the lipid matrix. They are surrounded by insoluble proteins with covalently bound lipids on their surface, creating the corneocyte lipid envelope. The aim of this diploma thesis was to prepare models of the human skin barrier using an isolated stratum corneum with a preserved corneocyte lipid envelope and without a preserved corneocyte lipid envelope, and then monitor and compare the lipid arrangements in these models. Obtaining the stratum corneum from the skin samples was necessary to prepare the models. Human skin lipids were extracted from isolated stratum corneum and part of this delipidated stratum corneum was saponified. Skin lipids were purificated by column chromatography, and their...
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Novel amino-decorated polyamidoamine dendrimers with ethylenediamine core: Synthesis and potential application in (trans)dermal drug delivery
Langerová, Martina ; Paraskevopoulos, Georgios (advisor) ; Kováčik, Andrej (referee)
Dendrimers are characterized as synthetic, spherical macromolecules with tree- like branched structures. Their well-controlled sizes (3 - 10 nm), ease of functionalization, high water solubility, well-defined chemical structure, and biocompatibility make these nanomaterials attractive for a wide spectrum of promising biomedical applications. Peptide dendrimers and polyamidoamine (PAMAM) dendrimers have been used to date as effective transdermal or topical drug delivery systems, with the latest in a much greater extent. The structural characteristics of the aforementioned molecules guided us to design a novel repeating unit for dendrimers (monomer) possessing amino branching point and able to afford generation expanding through repeating amide bonds. The novel monomer, after appropriate modifications, was used to develop lower generations of polyamidoamino dendritic structures having amide groups and amino-branching points in their interior. The new dendrimers were isolated and fully characterized by typical spectroscopic technics. The final molecules will be used in human skin permeation experiments and will be evaluated for their effect on skin permeability.
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Effect of glucosyl sphingosine on the stratum corneum permeability
Bataalla, Omar Mahrous Farid ; Kováčik, Andrej (advisor) ; Svačinová, Petra (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of pharmaceutical technology Candidate: Omar Mahrous Farid Bataalla Supervisor: PharmDr. Andrej Kováčik, Ph.D. Consultant: Dr. Georgios Paraskevopoulos, PhD. Title of Thesis: Effect of Glucosyl Sphingosine on the stratum corneum Permeability Glucosyl sphingosine (GSP) belongs to a large lysolipid subclass of sphingolipids, which is formed from ceramide (Cer) precursors by its hydrolysis. Patients with some skin diseases, such as atopic dermatitis, have lower amounts of barrier Cer in comparison to a healthy skin. As a result, they have higher quantity of GSP with low moisture content due to impaired barrier function. The aim of my work was to investigate the effect of GSP on skin permeability (in this thesis, the uppermost epidermal layer, the stratum corneum, was used) by using four permeability markers, trans-epidermal water loss (TEWL), electrical impedance, flux of theophylline and flux of indomethacin. The electrical impedance showed higher permeability to ions in tissues with GSP (statistically significant) in comparison to the controls. An addition of GSP also increased the permeability to water, small polar molecules and large lipophilic molecules (both statistically insignificant). I also investigated the role of GSP on...
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Study of microstructure of skin barrier model using deuterated ceramides
Juhaščik, Martin ; Kováčik, Andrej (advisor) ; Paraskevopoulos, Georgios (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Technology Author: Martin Juhaščik Supervisor: PharmDr. Andrej Kováčik, Ph.D. Title of diploma thesis: Study of microstructure of skin barrier model using deuterated ceramides Ceramides (Cer) are sphingolipids, which participate in eucaryotic cells in various biological processes (cell signalling, proliferation, differentiation and cell apoptosis). In mammalian skin, Cer are localized in the uppermost layer of epidermis, stratum corneum (SC). In this layer, Cer along with cholesterol (Chol) and free fatty acids form multilayer lamellae of intercellular lipid matrix. The skin lipid arrangement in SC is still unclear. To evaluate the skin lipid arrangement, skin membrane models with labelled (deuterated) lipids have been used. Therefore, the aim of this work was to synthesize sphingosine with deuterated chain and Cer based on deuterated sphingosine, i.e., N-lignoceroyl sphingosine-d28 (with lignoceric acid acyl (C24); d-CerNS) and N-lignoceroyl-d47 sphingosine-d28 (dd-CerNS) and to study their phase behaviour and arrangement in model membranes by using biophysical studies. Synthesis of deuterated Cer started from elimination of 1-pentadecanol-d31 to obtain a deuterated terminal alkene. Next, a vinylation of...
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Study of free sphingoid bases in skin barrier
Jarešová, Zuzana ; Kováčik, Andrej (advisor) ; Vraníková, Barbora (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Technology Author: Zuzana Jarešová Supervisor: PharmDr. Andrej Kováčik, Ph.D. Consultant: PharmDr. Lukáš Opálka, Ph.D. Title of diploma thesis: STUDY OF FREE SPHINGOID BASES IN SKIN BARRIER The skin barrier, localized in the stratum corneum (SC), consists of corneocytes and an intercellular matrix formed from three types of lipids - ceramides, free fatty acids, and cholesterol, represented in an equimolar ratio. The overall arrangement of lipids is organized and highly specialized. Ceramides are structurally formed from the fatty acid acyl attached to a sphingoid base. In minor but not insignificant amounts, free sphingoid bases can also be found in the skin barrier. Several studies show that there is an increased concentration of free sphingoid bases in skin barrier disorders, such as atopic dermatitis. Although it is assumed that the presence of free sphingoid bases affects the skin barrier, it is not elucidated the way of their participation till today. The lack of studies or their diverse results leads us to the main goal of this thesis - to clarify how free sphingoid bases influence the skin barrier. In this work, the model membranes were prepared by the isolation of human SC ex vivo. Sphingosine (S),...
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Study of sphingosine, dihydrosphingosine and phytosphingosine in skin barrier models
Kubátová, Denisa ; Kováčik, Andrej (advisor) ; Svačinová, Petra (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Technology Author: Denisa Kubátová Supervisor: PharmDr. Andrej Kováčik, Ph.D. Consultant: PharmDr. Lukáš Opálka, Ph.D. Title of diploma thesis: Study of sphingosine, dihydrosphingosine and phytosphingosine in skin barrier models The stratum corneum (SC), the uppermost layer of the skin, localized in the uppermost part of the epidermis, represents the skin barrier of the organism. SC is composed of corneocytes and an intercellular lipid matrix, which is formed by ceramides (Cer), free fatty acids (FFA), and cholesterol (Chol) in an equimolar ratio. Substances from the group of sphingolipids - Cer, are sphingoid bases (for example, sphingosine (S), dihydrosphingosine (dS), phytosphingosine (P)) acylated with a fatty acid (for example, lignoceric acid (LIG)). In the lipid matrix, the metabolic products of Cer (free sphingoid bases) are also present, but their role in SC barrier functions is not clear. Some studies show that Cer with different sphingoid bases, and increased presence of free sphingoid bases, can lead to a change in the permeability of the skin barrier. This work aimed to study the effect of permeability of sphingoid bases on the model membrane permeability. Nine types of membranes were prepared; they...
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Effect of combination of mucoadhesive polymers on the behaviour of matrix tablets in the gastric environment.
Johnová, Karolína ; Vraníková, Barbora (advisor) ; Kováčik, Andrej (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of: Pharmaceutical Technology Mentor: PharmDr. Barbora Vraníková, Ph.D. Consultant: Mgr. Chiazor Ugo Ogadah Student: Karolína Johnová Title of Thesis: Effect of combination of mucoadhesive polymers on the behaviour of matrix tablets in the gastric environment Colon-targeted drug delivery plays a significant role in the pharmacotherapy of local diseases situated in the large intestine (colorectal cancer, inflammatory bowel diseases etc.). In terms of sustained drug release, such formulations carrying the active substance must be resistant to the acidic environment of the upper gastrointestinal tract. In addition, an enhanced therapeutic efficacy may be achieved by prolonging the residence time of the formulation at the absorption site by means of mucoadhesive drug delivery systems. For these reasons, the presented preformulation study investigates the behaviour of matrix tablets based on mucoadhesive polymers in the gastric environment. Knowledge of the system behaviour in acidic pH is important as the surrounding of an inflammatory colon may be lower in comparison to the physiological conditions. The selected polymers, guar gum (GK) and hydroxypropyl methylcellulose K15M (HPMC K15M) were used separately or combined in ratios...
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