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Development of liquisolid systems for colon targeting
Ogadah, Chiazor Ugo ; Vraníková, Barbora (advisor) ; Zámostný, Petr (referee) ; Gajdziok, Jan (referee)
Univerzita Karlova, Farmaceutická Fakulta V Hradci Králové Školicí pracoviště: Katedra Farmaceutické Technologie Doktorský studijní program: Farmaceutická Technologie Kandidátka: Mgr. Chiazor Ugo Ogadah Školitelka: doc. PharmDr. Barbora Vraníková, Ph.D. Konzultantka: doc. Prof. PharmDr. Zdeňka Šklubalová, Ph.D. Název dizertační práce: Vývoj liquisolid systémů s cíleným přívodem léčiva do kolonu V lokální nebo systémové terapii chorob tlustého střeva mají systémy cílící do kolonu slibnou perspektivu. Úspěch však představuje výzvu díky fyziologickým bariérám trávicího traktu. Pokud zvýšení rozpustnosti léčiva předchází cílení, lze rozpouštění, jako krok limitující rychlost, obejít, urychlit vstřebání léčiva a zvýšit jeho perorální biodostupnost. Pro optimalizaci dávky a terapeutického efektu je kromě toho potřebné zadržet přípravek v místě cílení. Cílem této práce je proto vývoj systému pro doručení a cílení omezeně rozpustného léčiva cyklosporinu A (CyA) do kolonu. V první části experimentu byly využity preformulační studie k dosažení zvýšené rozpustnosti a zrychleného uvolnění CyA pomocí tzv. liquisolid sytému (LSS) nebo přípravou interaktivních směsí společným mletím (komletím). To zahrnovalo výběr vhodného nosiče a hodnocení jeho vlastností při mletí, stejně jako výběr netěkavého...
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Study and Evaluation of Topically Applied Ceramides onto Disrupted Skin Barrier
Svobodová, Marie ; Kováčik, Andrej (advisor) ; Vraníková, Barbora (referee)
Department of Pharmaceutical Technology Author: M S b S , Ph.D. Title of diploma thesis: Study and Evaluation of Topically Applied Ceramides onto Disrupted Skin Barrier Skin is the largest organ of the human body and serves several key functions, such as protection against external influences and regulation of body temperature. Healthy skin is able to maintain the integrity and stability of the organism due to its complex structure. The skin is composed of several layers of cells, including the stratum corneum (SC), which forms the main protective barrier. Ceramides (CER) are one of the main types of barrier lipids found in the SC. These lipid molecules, along with other lipids, create a hydrophobic matrix that protects the skin from dehydration and other external influences. The lack of CER in the skin barrier leads to the disruption of its function and the worsening of the skin condition. This is associated with many diseases, such as dermatitis, psoriasis, and others. The study of CER in the SC is important to understand the mechanisms of skin protection and to develop new therapeutic approaches for the treatment of skin diseases. Topical administration of barrier lipids, especially CER, is one possible treatment route for skin diseases. Therefore, the aim of this work was to prepare...
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Evaluation of compressibility of tableting mixtures containing different amount of sodium stearyl fumarate
Chrzová, Iryna ; Svačinová, Petra (advisor) ; Vraníková, Barbora (referee)
Charles University, Faculty of Pharmacy in Hradec Králové This thesis deals with the evaluation of the compressibility of tablets with different content of sodium stearyl fumarate (SSF). A mixture of microcrystalline cellulose and lactose in a 1:1 ratio was used as a model substance. The glidant sodium stearyl fumarate was added at concentrations of 0.5%, 1%, 1.5% and 2%. Subsequently, the tablets were pressed at a compression force of 5 kN, 7 kN and 10 kN using force- displacement record. The energy profile of the compression process was recorded, and the ejection force was also evaluated. Then crushing force, disintegration time, friability and true density were measured. The values of tensile strength, porosity, axial and volume relaxation characterizing the properties of prepared tablets were calculated from the obtained results. During the evaluation of the energy profile, it emerged that E1, E2, E3, Elis and Emax increase with increasing pressing force. The addition of SSF has minimal effect on the energy profile. At a concentration of 0.5% and 1% of SSF, the highest axial relaxation was measured, concentrations of 1.5% and 2% had no effect on the relaxation of the tablets. A decrease in volume relaxation occurred at all compression forces and concentrations of SSF. The most significant...
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Study of the effect of biomolecules on the solubility of poorly soluble drugs
Kheirabadi, Fatemeh ; Holas, Ondřej (advisor) ; Vraníková, Barbora (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Technology Supervisor: Dr. Ondrej Holas, Ph.D. Consultant: prof. Anette Müllertz, Ph.D. Student: Fatemeh Kheirabadi Title of thesis: Effects of Proteins on Apparent Drug solubility in Fasted State Stimulated Colonic Fluids This thesis investigates the influence of proteins on the apparent solubility of drugs in fasted state stimulated colonic fluids. The investigation was conducted on a selection of compounds with varying physicochemical and plasma protein binding properties. Precisely, three different compounds named as Nilotinib, Carvedilol and Ritonavir were analyzed for their apparent solubility in three distinct protein sources: bovine serum albumin, mucin from dehydrated porcine gastric mucin type II, and collected porcine intestinal mucus. Accurate reversed-phase high-performance liquid chromatography was developed and employed as the analytical method to determine the concentration of the apparent drug solubility of the investigated compounds. The research on the solubility of poorly soluble compounds in simulated colonic fluids has been restricted. Additionally, factors such as the impact of proteins remains unexplored in biorelevant media, which could be critical for enhancing our understanding of drug...
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Efect of the composition of an emulsion with imunosupressant on the rhelogical properities of the emulsion
Martinek, Vojtěch ; Šnejdrová, Eva (advisor) ; Vraníková, Barbora (referee)
Charles University Faculty of Pharmacy in Hradec Kralove Department of Pharmaceutical Technology Author: Mgr. Vojtěch Martinek Title of thesis: Efect of the composition of an emulsion with imunosupressant on the rhelogical properities of the emulsion Supervisor: PharmDr. Eva Snejdrova, Ph.D. This thesis evaluates rheological properties of the emulsion created after mixing the drug product Cyclosporine Oral Solution, USP /MODIFIED/ 100 mg/ml with water in different ratios. The theoretical part describes general characteristics, stability and viscosity of emulsions. It also describes self-emulsifying systems and the tested product Cyclosporine Oral Solution, USP /MODIFIED/ 100 mg/ml. In the experimental part of the work, the type of emulsion created, its flow properties and the effect of homogenization intensity were characterized. It was experimentally verified that as the amount of water in the mixture increases, first a w/o emulsion is formed and then the emulsion turns to an o/w emulsion type. In terms of flow properties, the medicinal product exhibits Newtonian behavior. By gradually adding water, the behavior changes to non-Newtonian up to a water:product ratio of 70:30, where the minimum value of the flow behavior index is found. As water is further added, the properties change back to...
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Study of disintegration time of capsules containing liquisolid systems
Bartůňková, Denisa ; Vraníková, Barbora (advisor) ; Svačinová, Petra (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of: Pharmaceutical Technology Supervisor: doc. PharmDr. Barbora Vraníková, Ph.D. Consultant: MSc. Andreas Niederquell Candidate: Denisa Bartůňková Title of Diploma Thesis: Study of disintegration time of capsules containing liquisolid systems Liquisolid (LS) systems are free-flowing powder formed by dispersing a drug that is sorbed into a carrier. The resulting powder may be subsequently processed into the final dosage form (tablet, hard gelatine capsules and pellets). However, there is a risk of interactions between the solvent used and the capsule shell, which could affect its rate of disintegration. Therefore, this study is focused on the preparation of liquisolid capsules (LSC) and the evaluation of their disintegration rate in various media. Tested LSC contained pure solvents (polyethylene glycol 200 - PEG 200, polyethylene glycol 400 - PEG 400 or Transcutol ® HP - T-HP) or dispersion of cyclosporine A (cysA) in the above-mentioned solvents sorbed into a carrier material Neusilin® US2 (NUS2). The evaluation of LSS showed that LSC have a longer disintegration time compared to capsules containing only NUS2. However, LSC with both types of PEGs disintegrated more slowly than those with T-HP. Moreover, different...
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The effect of solvent on disintegration time of liquisolid systems in the form of capsules
Helerová, Ladislava ; Vraníková, Barbora (advisor) ; Šklubalová, Zdeňka (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of: Pharmaceutical Technology Mentor: doc. PharmDr. Barbora Vraníková, Ph.D. Consultant: MSc. Andreas Niederquell Student: Ladislava Helerová Title of Thesis: The effect of solvent on disintegration time of liquisolid systems in the form of capsules According to the literature, the resulting liquisolid (LS) powders may be formulated into the form of tablets, pellets or hard gelatine capsules. However, the available resources about liquisolid systems do not consider possible interactions between the used excipients and capsule shell. Carriers can adsorb the water from the gelatine capsule and hence cause its brittleness, while the solvent can penetrate the capsule shell and thereby affects its integrity and properties. For these reasons, LS capsules containing mixtures of the carrier Neusilin® US2 (NUS2) with different amounts of propylene glycol (PG), polysorbate 80 (PS 80) or the cyclosporine A (CysA) dispersions in these solvents were prepared and tested. The disintegration time in three dissolution media, differential scanning calorimetry (DSC) and infrared spectroscopy (IR) were evaluated to study the changes in the capsule properties. The obtained results showed that the disintegration time of LS capsules was prolonged...
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Study and Evaluation of Topically Applied Ceramides onto Disrupted Skin Barrier
Svobodová, Marie ; Kováčik, Andrej (advisor) ; Vraníková, Barbora (referee)
Department of Pharmaceutical Technology Author: M S b S , Ph.D. Title of diploma thesis: Study and Evaluation of Topically Applied Ceramides onto Disrupted Skin Barrier Skin is the largest organ of the human body and serves several key functions, such as protection against external influences and regulation of body temperature. Healthy skin is able to maintain the integrity and stability of the organism due to its complex structure. The skin is composed of several layers of cells, including the stratum corneum (SC), which forms the main protective barrier. Ceramides (CER) are one of the main types of barrier lipids found in the SC. These lipid molecules, along with other lipids, create a hydrophobic matrix that protects the skin from dehydration and other external influences. The lack of CER in the skin barrier leads to the disruption of its function and the worsening of the skin condition. This is associated with many diseases, such as dermatitis, psoriasis, and others. The study of CER in the SC is important to understand the mechanisms of skin protection and to develop new therapeutic approaches for the treatment of skin diseases. Topical administration of barrier lipids, especially CER, is one possible treatment route for skin diseases. Therefore, the aim of this work was to prepare...
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Study of influence of hydrophilic carriers on the solubility of a poorly soluble drug
Veselá, Eliška ; Šklubalová, Zdeňka (advisor) ; Vraníková, Barbora (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of: Department of Pharmaceutical Technology Supervisor: Doc. PharmDr. Zdeňka Šklubalová, Ph.D. Consultant: Mgr. Jana Brokešová Student: Eliška Veselá Title of Thesis: Study of influence of hydrophilic carriers on the solubility of a poorly soluble drug The aim of this thesis was to enhance the solubility of a poorly soluble model drug meloxicam (MLX) by preparing binary interactive mixtures with hydrophilic carriers by simple mixing and co-milling. The mixtures were characterized for granulometric properties. The dissolution studies were carried out using the USP-4 apparatus assembled with a flow-through powder cell in an open-loop system. The dissolution rate rrel (min-1 ) and the amount of released drug mrel (%) were evaluated. The observable positive effect of carriers was registerred in terms of increasing the dissolution rate and the amount of released drug for both mixed and co-milled mixtures comparing to the raw drug. Mixtures with hypromellose were the exception; the improvement of the monitored parameters was not detected.
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Formulation and characterization of hydrogels for local treatment of musculoskeletal infections
Drdová, Pavlína ; Šnejdrová, Eva (advisor) ; Vraníková, Barbora (referee)
Charles University Faculty of Pharmacy in Hradec Kralove Department of Pharmaceutical Technology Author: Pavlína Drdová Title of thesis: Formulation and characterization of hydrogels for local treatement of musculoskeletal infection Supervisor: PharmDr. Eva Šnejdrová, Ph.D. Local anti-infective therapy for musculoskeletal infections eliminates systemic drug toxicity. By selecting a suitable drug delivery system, higher drug concentrations at the site of infection and sustained release can be achieved. Such a system may be gels, formulated and tested in the submitted diploma thesis. The theoretical part of the work was devoted to the description of musculoskeletal infections and their treatment, characterization of gels and their use in parenteral administration. Hydrophilic gels based on hypromellose, carrageenan, gelatin and fish gelatin containing vamcomycin hydrochloride and gentamicin sulfate were formulated. Flow and viscoelastic properties were tested on a rotational rheometer. The analysis of flow curves by the Power law model proved a non-Newtonian type of flow. The most sensitive to applied stress is a 3 % hypromellose gel, the least a dispersion of iota-carrageenan with povidone 25. Viscoelastic properties were evaluated based on elastic, viscous and complex modulus, phase angle and yield...
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