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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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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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Investigation of process parameters and their influence on spray dried particles properties
Grázová, Marcela ; Svačinová, Petra (advisor) ; Kováčik, Andrej (referee)
1. ABSTRACT Charles University, Faculty of Pharmacy in Hradec Králové Department of: Pharmaceutical Technology Supervisor: PhamDr. Petra Svačinová, Ph.D. Consultant: Ing. Petr Koukal, Ph.D. Student: Marcela Grázová Title of Thesis: Investigation of process parameters and their influence on spray dried particles properties. The aim of the thesis was to determine to what extent it is possible to influence the particle size of the products by setting the parameters of the dryer. This particle size largely depends on the scale of the dryer used. Therefore, the aim was to determine whether a laboratory-scale spray dryer can either produce particles of variable size or particles of such size, that is typically obtained from production-scale devices. Particles prepared of meloxicam dispersions in hydroxypropylmethylcellulose phthalate were used for evaluation. A variety of input parameters for spray drying (drying gas inlet temperature, stock solution flow, concentration, and spray nozzle diameter) was used to prepare several batches of the product. The methodology Design of Experiments was used to identify the influence of individual input parameters on the product properties (particle size, glass transition temperature, and residual solvent content). Individual batches of the products were characterized by 1 H...
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Calcium phosphate bone cements: Synthesis, Characterization and drug release properties
Doubek, Jiří ; Paraskevopoulos, Georgios (advisor) ; Kováčik, Andrej (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Technology Author: Jiří Doubek Supervisor: Dr. Georgios Paraskevopoulos, Ph.D. Title of Thesis: Calcium phosphate bone cements: Synthesis, characterization and drug release properties Non-healing bone traumas are currently a complication, which may disable a patient from active life for a long period. Due to the fact that bone mass consists mostly of hydroxyapatite, a derivative of calcium phosphate - calcium phosphate cement (CPC) - is studied as an injectable bone substitute. The cement's characteristics (low setting temperature, injectability, bioactivity, and resorbability) are very promising. Furthermore, the possibility to incorporate a drug in the formulation that would support the healing process opens a way for new therapeutic options. Firstly, the aim of this research was to synthesize a high-quality α-tricalcium phosphate (α-TCP) and characterize its properties. Subsequently, the prepared α-TCP was used for the preparation of an injectable and washout resistant cement paste. Finally, the properties of developed pure or ibuprofen-loaded cement were examined by X-ray diffraction, Raman spectra, compressive strength, scanning electron microscopy, and dissolution studies. The obtained data revealed that...
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In vitro study of topical use of cidofovir
Sedláčková, Martina ; Vávrová, Kateřina (advisor) ; Kováčik, Andrej (referee)
Martina Sedláčková In vitro study of topical use of cidofovir Pharmaceutical faculty in Hradec Králové, Charles University Abstract Cidofovir (CDV), an antiviral drug belonging to the group of acyclic nucleoside phosphonates, is a highly potent drug used for treatment of various infections of viral origin. The low usage of CDV is caused by its price. This work deals with possibilities of increasing the concentration and availability of CDV r in the skin that could lead to lowering of the production costs of the preparations containing this substance. The goal of this work was to study the concentration of CDV in different skin layers after its application on intact and tape striped human skin. The effect of permeation enhancer 6-(dimethylamino)hexanoic acid dodecyl ester was also investigated. Both attitudes were investigated in vitro using modified Franz diffusion cells. Three different concentration of CDV (0.3%, 1% and 3%) were applied on the intact or tape-stripped skin with or without 1% enhancer. In intact skin, the combination of 3% CDV with 1% enhancer provided epidermal CDV concentration of 1115 µg/g, which is 1.45-times higher than without an enhancer. In tape-striped skin, the epidermal concentration of CDV increased to 2584 µg/g which is 1.55-times higher than without enhancer. The highest...
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Calcium phosphate bone cements: Synthesis, Characterization and drug release properties
Doubek, Jiří ; Paraskevopoulos, Georgios (advisor) ; Kováčik, Andrej (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Technology Author: Jiří Doubek Supervisor: Dr. Georgios Paraskevopoulos, Ph.D. Title of Thesis: Calcium phosphate bone cements: Synthesis, characterization and drug release properties Non-healing bone traumas are currently a complication, which may disable a patient from active life for a long period. Due to the fact that bone mass consists mostly of hydroxyapatite, a derivative of calcium phosphate - calcium phosphate cement (CPC) - is studied as an injectable bone substitute. The cement's characteristics (low setting temperature, injectability, bioactivity, and resorbability) are very promising. Furthermore, the possibility to incorporate a drug in the formulation that would support the healing process opens a way for new therapeutic options. Firstly, the aim of this research was to synthesize a high-quality α-tricalcium phosphate (α-TCP) and characterize its properties. Subsequently, the prepared α-TCP was used for the preparation of an injectable and washout resistant cement paste. Finally, the properties of developed pure or ibuprofen-loaded cement were examined by X-ray diffraction, Raman spectra, compressive strength, scanning electron microscopy, and dissolution studies. The obtained data revealed that...
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Permeation of nanoparticles through sublingual membrane 3
Dvořáková, Pavlína ; Doležal, Pavel (advisor) ; Kováčik, Andrej (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of pharmaceutical technology Candidate: Mgr. Dvořáková Pavlína Consultant: doc. RNDr. Pavel Doležal, CSc. Title of Thesis: Permeation of nanoparticles through sublingual membrane 3. In the theoretical part, attention was paid to the entry of drugs into the body by the sublingual route, description of the oral cavity (mucosa, epithelium, mucus, saliva, MCGs), OCCAT model, and basic concepts of bioimpedance. In the experimental part, the hydrodynamic size of the PD-Chromeon 470 nanoparticles was verified by the DLS method. In the environment of water, even two buffers pH 6.8 and 7.4 according to Sörensen, practically identical results were obtained at the level of 40 nm. Buffers were used as donor, resp. acceptor phase in vitro permeation experiments. The experiments included measurement of impedances of differently processed and stored sublingual membranes from pig tongue. To test the penetration of nanoparticles through these model mucosal barriers, nanoparticles were applied in a concentrated (500 µg / ml), diluted (1: 4) dispersion. The lowest impedance had the sodium azide-preserved membranes, which were frozen at -18 ř C for a long time. These also showed the highest in vitro permeation values of nanoparticles. Rapid...
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Effect of temperature and solution concentration on the properties of spray-dried lactose using the nozzle with diameter of 2 mm.
Pavelková, Nikola ; 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: Nikola Pavelková Title of Thesis: Effect of temperature and solution concentration on the properties of spray-prepared lactose using the nozzle with diameter of 2 mm Spray drying is a method used in various industry fields. The principle is the conversion of a substance in the liquid state into solid dry particles. By spray drying it is possible to obtain a suitable product with the desired properties, which depends on the various process parameters. The aim of the work is to determine the influence of temperature and concentration of the solution on the properties of spray-prepared lactose using a nozzle with a diameter of 2 mm. Solutions of 15 % and 20 % lactose were prepared and dried at inlet temperatures of 150 - 210 řC. The shape and size of obtained particles were examined by optical microscopy. Thermal properties were evaluated using differential scanning calorimetry. At 15 % concentration, most of the spray-dried lactose particles occurred in the size range 2,5 - 5 μm and 5 - 7,5 μm . At a concentration of 20 % it was between 2,5 - 5 μm. For both concentrations the minimum numbers of particles were smaller than 2,5 μm and larger than 15 μm....
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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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