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Evaluation of the influence of filler sort and lubricant type and concentration on the parameters of the compaction equation
Ondrejček, Pavel ; Rabišková, Miloslava (advisor) ; Vetchý, David (referee) ; Bělohlav, Zdeněk (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Department of pharmaceutical technology Candidate Mgr. Pavel Ondrejček Supervisor prof. PharmDr. Miloslava Rabišková, CSc. Title of Doctoral Thesis Evaluation of the influence of filler sort and lubricant type and concentration on the parameters of the compaction equation This thesis is dealing with an evaluation of the compaction process of pharmaceutical excipients and their mixtures. The effect of the filler type, lubricant type and its concentration on the parameters of the compaction equation developed by Assoc. Prof. RNDr. Milan Řehula, CSc. is studied. Microcrystalline cellulose Avicel PH-200, lactose Lactochem Fine Crystals and calcium hydrogen phosphate dihydrate Emcompress were used as model fillers. These fillers of similar particle size were selected because of different bonding mechanism and varying course of the compaction process. Fillers were evaluated individually and then in their blends with lubricants magnesium stearate, sodium stearylfumarate and Syloid, i.e. modified colloidal silica in concentration 0,5 and 1 %. Moisture content and flow properties were determined in individual fillers. Particle size distribution, scanning electron microscope pictures and specific surface area measurements were...
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Possibilities for in-vitro testing of controlled-release parenterals.
Kožák, Jan ; Řehula, Milan (advisor) ; Rabišková, Miloslava (referee)
The objective of this study was to start with the development of a gel-based medium simulating intramuscular environment for in-vitro drug release testing as an alternative to currently used water-based media. A pork meat was selected as a model of the muscle tissue. At the first part of the study, diffusion rate was proposed as the most determining factor of drug release in gel-based medium. Consequently, the diffusion rate of sodium fluorescein in pork meat was compared with the diffusion rate in various gels, namely gelatine, calcium alginate and different grades of hydroxypropyl methylcellulose (HPMC). The measurments were performed at 37řC with respect to recomendations for drug dissolution testing and in- vivo temperature. Gelatine however underwent a gel-sol transition at 37řC regardless to polymer concentration and showed to be unsuitable for measurement by selected method. The diffusion rate of fluorescein in all used gels was higher than the diffusion rate in the meat. Only 25% HPMC (Methocel E4M grade) showed acceptable similarity to meat, in terms of the diffusion rate, and was consequently selected for the second part of the study. In the second part of the study, the release of ibuprofen from ethylcellulose implants (ethylcelulose : ibuprofen weight ratio 9:1) in pork meat and 25%...
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Effect of Amino Acids Derivatives And Ceramides on Skin Barrier Function
Janůšová, Barbora ; Vávrová, Kateřina (advisor) ; Balgavý, Pavol (referee) ; Rabišková, Miloslava (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of inorganic and organic chemistry Candidate: Mgr. Barbora Janůšová Supervisor: doc. PharmDr. Kateřina Vávrová, Ph.D. Title of Doctoral Thesis: Effect of amino acids derivatives and ceramides on skin barrier function The main goal of my thesis was to contribute to the understanding of behavior of the ceramides and skin barrier function modulators based on amino acids derivatives, as well as to elucidate the relationship between their structure and activity. Transdermal permeation enhancers are compounds that temporarily decrease skin barrier properties to promote drug flux. In the first part of my thesis, enhancers with amino acids (proline, sarcosine, alanine, β-alanine, and glycine) attached to hydrophobic chain(s) via a biodegradable ester link were investigated. The double-chain lipid-like substances displayed no enhancing effect, whereas single-chain substances significantly increased skin permeability. The most active enhancer - proline derivative L-Pro2 reached enhancement ratios of up to 40 at 1% concentration, which is higher than that of the well-established and standard enhancers Azone, DDAIP, DDAK, and Transkarbam 12. No stereoselectivity was observed. L-Pro2 acted synergistically with propylene glycol and...
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Study of water-absorption of nanofibres made from hyaluronate derivatives.
Lebedová, Václava ; Šklubalová, Zdeňka (advisor) ; Rabišková, Miloslava (referee)
Charles University in Prague, Faculty of Pharmacy in Hradci Králové Department of: Pharmaceutical technology Consultant: Doc. PharmDr. Zdeňka Šklubalová, Ph.D. Ing. Jana Růžičková, Ph.D. Student: Václava Lebedová Title of Thesis: Study of water-absorption of nanofibres made from hyaluronate derivatives Micro and nanofibers have suitable properties to be used as dressing in healing of injuries. In this experimental work, I studied the properties of nanofibres made from new synthesized hyaluronate derivates (HA). The nanofibres were manufactured by electrospinning method using model version of 4SPIN. To modify properties of the aqueous solutions of HA, polyethylene oxide 400 000 was used. The resulting solutions had an appropriate surface tension, conductivity, and viscosity required to prepare nanofibres. The samples of nanofibres were crosslinked by UV radiation for 10 minutes (HA10) and/or 60 minutes (HA60). To study the influence of crosslinking on the sorption capacity of nanofibres, the free swell absorbency method was used in which samples were immersed in a bath containing water and/or a 0,9% aqueous solution of sodium chloride, respectively, for 5 minutes (liquor/fibre ratio of 75:1). The nanofibers crosslinked for 60 minutes had significantly larger absorbency of both liquid media than...
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Transdermal Permeation Enhancers: Study of Structure-activity Relationships.
Novotný, Michal ; Vávrová, Kateřina (advisor) ; Nobilis, Milan (referee) ; Rabišková, Miloslava (referee)
Permeation enhancers are compounds that promote drug flux into systemic circulation or adjacent tissues. This doctoral thesis follows our previous results and aims at studying two different groups of potential permeation enhancers: dicarboxylic acid derivatives and analogues of Transkarbam 12. The main purpose of my work was to study the structure- activity relationships in these permeation enhancers and to contribute to the elucidatation of their mechanism of action. The first part of my work was focused on derivatives of dicarboxylic acids. Series of enhancers based on maleic, fumaric, succinic, tartaric and meso-tartaric acids were prepared. The enhancing activity of these compounds was investigated in vitro in Franz diffusion cells using theophylline as a model drug and porcine skin. The single-chain amphiphiles were markedly more effective than the double-chain ones. The most active enhancer, monododecyl maleate, that is a cis- derivative, was a more potent enhancer than its respective trans- isomer. Furthermore, the activity of similar succinates, i.e. compounds having a single bond, strongly depended on the donor vehicle. No difference between diastereoisomeric tartaric and meso-tartaric acid derivatives was found. The second part of my work dealt with Transkarbam 12, an ammonium carbamate...
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Immunoprotective character of polymer cytotoxic drugs
Šírová, Milada ; Říhová, Blanka (advisor) ; Turánek, Jaroslav (referee) ; Rabišková, Miloslava (referee)
18 I. INTRODUCTION Cancer is a serious health problem worldwide. In economically developed countries, it is a second most frequent cause of death after cardiovascular dis- eases, and the number of oncological patients continuously increases with the increasing age of population. The mainstay of cancer therapy is combination of surgery, radiation and chemotherapy. Whilst surgery and radiation are relatively precise and suitable to achieve a local control over the tumor, chemotherapy exerts a systemic ef- fect. These three modalities, when properly combined and sequenced, can cure a substantial number of hematological cancers and a smaller, but still significant subset of various solid tumors. Most cytostatic/cytotoxic drugs that are now in common use target the cells with high proliferation rate. The non-selective character of chemotherapy leads to increased toxicities towards normal rapidly proliferating cells. This means that the drugs have to be used at suboptimal doses, leading to development of (multi)drug resistance, metastatic disease and, eventually, to failure of the therapy. Innovative therapeutic strategies need to be developed in order to achieve better treatment outcome. For that purpose, several approaches are be- ing applied. First, sophisticated genomic and proteomic research could identify...
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The Viscoelasticity of Pharmaceutical Fillers for Direct Tabletting
Adámek, Roman ; Řehula, Milan (advisor) ; Rabišková, Miloslava (referee) ; Špaček, Vladimír (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical technology Candidate: Mgr. Roman Adámek Supervisor: Doc. RNDr. Milan Řehula, CSc. Title of Doctoral Thesis: Viscoelasticity of fillers for direct tablet compacting Keywords: stress relaxation, viscoelasticity, Maxwell-Wischert model, hydrogen bond, van der Waals bond Important property of pharmaceutical fillers is viscoelasticity which can be evaluated in many ways. The Stress relaxation test is a method when a punch of compacting machine stops precisely in a moment of reaching set up pressure and decreasing pressure in a tablet during time is recorded. This action is mathematically described by a three-exponential equation which facilitates to separate the Stress relaxation test in three simultaneously running actions. Each of these actions is described by the moduli of plasticity and elasticity which point out in detail on viscoelastic properties of measured materials. The Stress relaxation test was used for 20 pharmaceutical fillers by 11 compacting pressures. To infer clearer conclusions, tablet strength, Young's modul of elasticity and elastic potential energy were determined. With help of above mentioned compacting parameters conclusions of viscoelasticity and compacting properties of used...
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Characterization of Compaction Process According to New Equation Parameters of Compaction
Rysl, Tomáš ; Řehula, Milan (advisor) ; Špaček, Vladimír (referee) ; Rabišková, Miloslava (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department: Department of galenic pharmacy Candidate: Mgr. Tomáš Rysl Supervisor: doc. RNDr. Milan Řehula CSc. Title of Doctoral Thesis: Characterization of compaction process according to new equation parameteres of compaction. The thessis deals with comparation of excipients used for production of tablets using new equations of tablet compaction. A lot of mathematical interpretations exist for determination of excipient behaviour during compaction process of tablet production. Obtained parameters of them express more or less possible behaviour of these excipients during compaction. The new mathematical interpretation was proposed for crystallic and polymeric materials. It seems to be very exact method to express compation process very correctly. 40 materials was evaluated according to this new proposed equation of compaction. Zwick/Roell Z050 was used to obtain this equation. Different behaviour of polymeric and crystallic materials has been found out. Behaviour of crystallic materials is interpreted by 2 phases, expressed by biexpoinencial equation. Behaviour of polymeric materials is interpreted by 3 phases, expressed by triexponencial equation. According to obtained paramateres, excipients have been described in term of...
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