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Polymeric stabilizers maintaining the supersaturation solubility of itraconazole nanocrystals after dissolution process
Kubačková, Jana ; Holas, Ondřej (advisor) ; Paraskevopoulos, Georgios (referee)
Title of thesis: Polymeric stabilizers maintaining the saturation solubility of itraconazole nanocrystals after dissolution process Author: Jana Kubačková Department: Pharmaceutical Technology Supervisor: PharmDr. Ondřej Holas, Ph.D. Specialized supervisor: Assoc. Prof. Leena Peltonen, Ph.D. The increase of bioavailability of poorly water soluble drugs is still an issue. One of the techniques improving aqueous drug substance solubility, and consequently enhancing bioavailability, is formation of nanoparticles. However, the bioavailability is determined by the concentration of the dissolved drug achieved at the time of absorption. This fact emphasizes the importance of the maintenance of the high solubility until the absorption area is reached. Sufficiently stabilised nanocrystalline drugs offer a solution to this problem. In this thesis, the solid nanoparticle formations of an antifungal agent itraconazole (ITZ) are presented. Wet milling was employed to create the nanosuspension stabilised by binary mixture of stabilisers or by a single stabiliser. An aggregation inhibitor Poloxamer 407 (F127) in the combination with a polymeric precipitation inhibitor hydroxypropyl methylcellulose (HPMC) or polyvinyl pyrrolidone (PVP) at different ratios, or a single precipitation inhibitor, were utilised. The...
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Preparation of pharmaceutical formulations based on polymeric and lipid carriers
Kubačková, Jana ; Zbytovská, Jarmila (advisor) ; Panáček, Aleš (referee) ; Štěpánek, František (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Technology Candidate Mgr. Jana Kubačková Supervisor Assoc. Prof. Jarmila Zbytovská, Mgr., Dr. rer. nat. Co-supervisor PharmDr. Ondřej Holas, PhD. Title of Doctoral Thesis Preparation of pharmaceutical formulations based on polymeric and lipid carriers Nanomedicine allows application of nanoscaled drug delivery carriers to achieve a therapy that can be tailored in terms of e.g. controlled release, site-specific delivery and protection of an active substance. From multiple nanoplatforms available for drug delivery, advantage was taken of biocompatible and biodegradable polymers and lipids to enable targeted intracellular delivery, delivery of a poorly water-soluble drug and delivery of a sensitive macromolecule. In the study with biodegradable polymeric nanomaterial we worked with experimental poly(lactic-co-glycolic acid) (PLGA) polymers. The formulations were optimised for targeting to phagocytic macrophages - of size up to 300 nm and negative surface charge. For this purpose, two linear and one branched PLGA were screened in combination with one of four surfactants in low concentrations (0.1-1%). These PLGA polymers were formulated into nanoparticles and loaded with a hydrophilic fluorescent dye Rhodamine B...
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Preparation of pharmaceutical formulations based on polymeric and lipid carriers
Kubačková, Jana ; Zbytovská, Jarmila (advisor) ; Panáček, Aleš (referee) ; Štěpánek, František (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Technology Candidate Mgr. Jana Kubačková Supervisor Assoc. Prof. Jarmila Zbytovská, Mgr., Dr. rer. nat. Co-supervisor PharmDr. Ondřej Holas, PhD. Title of Doctoral Thesis Preparation of pharmaceutical formulations based on polymeric and lipid carriers Nanomedicine allows application of nanoscaled drug delivery carriers to achieve a therapy that can be tailored in terms of e.g. controlled release, site-specific delivery and protection of an active substance. From multiple nanoplatforms available for drug delivery, advantage was taken of biocompatible and biodegradable polymers and lipids to enable targeted intracellular delivery, delivery of a poorly water-soluble drug and delivery of a sensitive macromolecule. In the study with biodegradable polymeric nanomaterial we worked with experimental poly(lactic-co-glycolic acid) (PLGA) polymers. The formulations were optimised for targeting to phagocytic macrophages - of size up to 300 nm and negative surface charge. For this purpose, two linear and one branched PLGA were screened in combination with one of four surfactants in low concentrations (0.1-1%). These PLGA polymers were formulated into nanoparticles and loaded with a hydrophilic fluorescent dye Rhodamine B...
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Generalization and specification of lexical meaning in contemporary translation of fiction
Kubáčková, Jana ; Jettmarová, Zuzana (advisor) ; Čermák, František (referee)
The aim of this thesis is to discuss the notions of generalization and specification as universal trends in translation and potential candidates for the status of universals of translation. Methods used in empirical research are also discussed in some detail. Chapters 1 and 2 focus on generalization and specification in the context of Descriptive Translation Studies, Corpus-Based Translation Studies and the work of the translation scholar Jiří Levý. Chapter 2 further attempts to present a comprehensive picture of both potential universals by examining the notion of lexical meaning and the issue of synonymy in the context of lexicology and stylistics. Finally, it draws attention to typological (systemic) differences between Czech and English and the impact these differences have on shifts of lexical meaning in terms of generalization/specification and on the use of electronic corpora. Chapter 3 outlines the three following stages of empirical research in terms of materials and methods. It presents a description of the three sets of corpora (a large monolingual comparable corpus, a parallel unidirectional English-Czech corpus, and a parallel corpus of one original and two translations), the choice of texts, reference corpora and corpus-processing software tools. Texts analysed in the three types of corpora...
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Polymeric stabilizers maintaining the supersaturation solubility of itraconazole nanocrystals after dissolution process
Kubačková, Jana ; Holas, Ondřej (advisor) ; Paraskevopoulos, Georgios (referee)
Title of thesis: Polymeric stabilizers maintaining the saturation solubility of itraconazole nanocrystals after dissolution process Author: Jana Kubačková Department: Pharmaceutical Technology Supervisor: PharmDr. Ondřej Holas, Ph.D. Specialized supervisor: Assoc. Prof. Leena Peltonen, Ph.D. The increase of bioavailability of poorly water soluble drugs is still an issue. One of the techniques improving aqueous drug substance solubility, and consequently enhancing bioavailability, is formation of nanoparticles. However, the bioavailability is determined by the concentration of the dissolved drug achieved at the time of absorption. This fact emphasizes the importance of the maintenance of the high solubility until the absorption area is reached. Sufficiently stabilised nanocrystalline drugs offer a solution to this problem. In this thesis, the solid nanoparticle formations of an antifungal agent itraconazole (ITZ) are presented. Wet milling was employed to create the nanosuspension stabilised by binary mixture of stabilisers or by a single stabiliser. An aggregation inhibitor Poloxamer 407 (F127) in the combination with a polymeric precipitation inhibitor hydroxypropyl methylcellulose (HPMC) or polyvinyl pyrrolidone (PVP) at different ratios, or a single precipitation inhibitor, were utilised. The...
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Generalization and specification of lexical meaning in contemporary translation of fiction
Kubáčková, Jana ; Čermák, František (referee) ; Jettmarová, Zuzana (advisor)
The aim of this thesis is to discuss the notions of generalization and specification as universal trends in translation and potential candidates for the status of universals of translation. Methods used in empirical research are also discussed in some detail. Chapters 1 and 2 focus on generalization and specification in the context of Descriptive Translation Studies, Corpus-Based Translation Studies and the work of the translation scholar Jiří Levý. Chapter 2 further attempts to present a comprehensive picture of both potential universals by examining the notion of lexical meaning and the issue of synonymy in the context of lexicology and stylistics. Finally, it draws attention to typological (systemic) differences between Czech and English and the impact these differences have on shifts of lexical meaning in terms of generalization/specification and on the use of electronic corpora. Chapter 3 outlines the three following stages of empirical research in terms of materials and methods. It presents a description of the three sets of corpora (a large monolingual comparable corpus, a parallel unidirectional English-Czech corpus, and a parallel corpus of one original and two translations), the choice of texts, reference corpora and corpus-processing software tools. Texts analysed in the three types of corpora...
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Generalization and specification of lexical meaning in contemporary translation of fiction
Kubáčková, Jana ; Jettmarová, Zuzana (advisor) ; Čermák, František (referee)
The aim of this thesis is to discuss the notions of generalization and specification as universal trends in translation and potential candidates for the status of universals of translation. Methods used in empirical research are also discussed in some detail. Chapters 1 and 2 focus on generalization and specification in the context of Descriptive Translation Studies, Corpus-Based Translation Studies and the work of the translation scholar Jiří Levý. Chapter 2 further attempts to present a comprehensive picture of both potential universals by examining the notion of lexical meaning and the issue of synonymy in the context of lexicology and stylistics. Finally, it draws attention to typological (systemic) differences between Czech and English and the impact these differences have on shifts of lexical meaning in terms of generalization/specification and on the use of electronic corpora. Chapter 3 outlines the three following stages of empirical research in terms of materials and methods. It presents a description of the three sets of corpora (a large monolingual comparable corpus, a parallel unidirectional English-Czech corpus, and a parallel corpus of one original and two translations), the choice of texts, reference corpora and corpus-processing software tools. Texts analysed in the three types of corpora...
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