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The use of milling and co-milling procedures for preparation of interactive mixtures
Jezerská, Jana ; Šklubalová, Zdeňka (advisor) ; Kvítek, Libor (referee) ; Vitková, Zuzana (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of: Pharmaceutical Technology Candidate: Mgr. Jana Jezerská Supervisor: doc. PharmDr. Zdeňka Šklubalová, Ph.D. Consultant: Ing. Jakub Koktan, Ph.D. Title of Doctoral Thesis: Utilization of technological procedures of milling and co-milling in the preparation of interactive mixtures The dissertation thesis is an annotated summary of the publication and research activities of the author, Mgr. Jana Jezerská (maiden name Brokešová). The thesis is focused on the preparation of binary interactive powder mixtures which consist of the micronized drug particles adhered onto the larger particles of an excipient (a carrier). The binary powder mixtures were prepared by mixing and/or co-milling and characterized by granulometric methods; crystallinity (thermal analysis, X-ray powder diffractometry), the flow properties (shear cell, avalanche properties) and the surface energy were evaluated as well. The dissolution rate of model drugs was estimated using a flow-through powder dissolution cell (USP-4). The used statistical model (central composite design) enabled to establish optimal milling conditions in a ball mill (the milling speed, the milling time, the size of milling balls) for five powder carriers. Based on quadratic response surface,...
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Study of the influence of tablet mixture composition on the flow and consolidation properties
Ferechová, Daniela ; Šklubalová, Zdeňka (advisor) ; Macho, Oliver (referee)
Charles University, Faculty of Pharmacy in Hradci Králové Department of: Supervisor: Pharmaceutical Technology doc. PharmDr. Zdeňka Šklubalová, Ph.D. Consultant: Mgr. Jana Brokešová Student: Daniela Ferechová Title of Thesis: Study of the influence of tablet mixture composition on the flow and consolidation properties Good flow properties of a tabletting mixture play an important role in the manufacturing of tablets. Flow behaviour of the commercial (original) tabletting mixture with poor flowability was evaluated in this thesis. The main aim was to find alternative fillers that may improve its flow. The granulometric characteristics and flowability of eight types of lactose and microcrystalline cellulose and their binary mixtures were studied. In comparison to the original tabletting mixture, the proposed modified one with both original fillers were replaced with new ones showed significantly better flow properties with steady state flow through the hopper orifice having a diameter of 10 mm. The results were confirmed using powder rheometer. The lower shear stress necessary to achieve flow under different normal loads as well as approximately 72 times lower cohesion value were detected for the modified tabletting mixture.
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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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Effect of mesoporous carrier on the properties of hydrophilic matrix based on guar gum.
Šnajdrová, Lucie ; Vraníková, Barbora (advisor) ; Šklubalová, Zdeňka (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of: Pharmaceutical Technology Mentor: doc. PharmDr. Barbora Vraníková, PhD. Consultant: Mgr. Chiazor Ugo Ogadah Student: Lucie Šnajdrová Title of Thesis: Effect of mesoporous carrier on the properties of hydrophilic matrix based on guar gum The treatment effectiveness can be significantly increased by targeting the drug delivery on a specific tissue. Therefore, colon targeting is desirable for the treatment of a range of local diseases (e.g., Crohn's disease). The drug can be delivered to the colon by various strategies while the oral route is preferred due to the patient compliance.1 The combination of several formulation strategies represents one of the most promising approaches in colon targeting. For this reason, the presented study aims at preformulation studies of liquisolid systems combined with mucoadhesive matrix systems. The presence of the silicate carrier Neusilin® US2 (NUS2) with a great absorption capacity can affect the performance of mucoadhesive polymers. Especially, mucoadhesion and swelling ability connected to the dissolution of the drug may be influenced upon preparation of these novel colon targeted drug delivery systems. Accordingly, tablets containing guar gum and NUS2 in different ratios were subjected to...
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Compatibility study of excipients and active substance in tablet mixtures
Křikava, Jakub ; Šklubalová, Zdeňka (advisor) ; Svačinová, Petra (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of: Pharmaceutical technology Mentor doc. PharmDr. Zdeňka Šklubalová, Ph.D. Consultant: Mgr. Daniel Pěček Student: Jakub Křikava Title of Thesis: Compatibility study of excipients and active substance in tablet mixture The aim of this work was to study interactions between lubricants and disintegrants used in the tablet mixtures for direct compression with high content of a drug. Binary mixtures of the drug and a selected excipient were prepared in the 1:1 ratio and that used in tablets. Modified tablet mixtures in which one of the excipients was excluded were prepared as well. The mixtures were subjected to the stress tests at the higher temperature/humidity. The influence on the thermal characteristics, porosity, the tensile strength and disintegration time of tablets was studied. Results showed that crospovidone interacts with a drug what worsened the properties of tablets and this negative effect was forced in the presence of stearic acid. Combination of crospovidone and stearic acid in tablet mixture increased the tablet tensile strength and disintegration time significantly. This combination cannot be recommended for the preparation of tablets. In case of the used drug, crosscarmellose sodium represents the better disintegrant.
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Formulation and processing of pharmaceutical nanosuspensions
Lehocký, Róbert ; Štěpánek, František (advisor) ; Šklubalová, Zdeňka (referee) ; Rajniak, Pavol (referee)
The pharmaceutical industry has been bringing an increasing number of innovative active ingredients from BCS Groups II and IV to the market in recent decades. Among other things, these substances are characterized by very low solubility in water. In order for these sparingly soluble substances to be used effectively in the treatment of patients, it is necessary to increase their solubility and thus induce a sufficient plasma concentration. One way to solve this problem is to adjust the crystal size of the drug substance to the level of micro- and nanoparticles. Thanks to particle size adjustment, it is possible to adjust the specific surface and thus control the solubility and overall dissolution profile of the drug. The thesis is divided into three parts. The first part deals with the effective preparation of a nanosuspension of sparingly soluble prodrug by means of nanomilling and subsequent transfer and scale-up from a batch to a flow-through bead mill by a novel method based on the effective number of passes. The second part concentrates on the description of an adverse but interesting effect - the occurrence of the so called Pickering foam, which is formed during the grinding process in a flow-through bead mill. The work explains the mechanism of Pickering foam formation and suggests a way to...
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Influence of mixing conditions of microcrystalline celluloses with lubricants on compression process and tablet strength.
Mastná, Eliška ; Mužíková, Jitka (advisor) ; Šklubalová, Zdeňka (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department: Pharmaceutical Technology Student: Eliška Kučerová Consultant: Assoc. Prof. PharmDr. Jitka Mužíková, Ph.D. Title of the Diploma Thesis: Influence of mixing conditions of microcrystalline celluloses with lubricants on compression process and tablet strength. This work evaluates the influence of a type of mixing device and mixing time of three types of microcrystalline cellusoses (MCC) with lubricants on compression process and tablet strength. Microcel® MC 102, MC 200 and Prosolv® SMCC 90 are used as dry binders. Magnesium stearate and sodium stearyl fumarate at 1% concentration are used as lubricants. Two types of mixing devices are used to mix powders, a mixing cube and a 3D Turbula mixer. Mixing time is 2 or 4 minutes. All tablets are compressed by compression force of 5 kN on the Zwick / Roell T1-FRO 50 material tester. The compressibility is evaluated by the energy profile of compression process, sensitivity to the addition of lubricants is characterized by lubricant sensitivity ratio values (LSR). The total energy of compression of all MCC decreases with the addition of both types of lubricants and with longer mixing time, more in the case of mixing in the cube. The highest values of the total energy of compression and at...
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A study of the influence of co-processed dry binder type on the properties of oraly disintegrating tablets with the drugs domperidone and lisinopril.
Jáglová, Kateřina ; Mužíková, Jitka (advisor) ; Šklubalová, Zdeňka (referee)
Charles University, Faculty of Pharmacy in Hradci Králové Department of: Pharmaceutical Technology Mentor: Assoc. Prof. PharmDr. Jitka Mužíková, Ph.D. Consultant: Mgr. Thao Tranová Student: Kateřina Jáglová Title of Thesis: A study of the influence of co-processed dry binder type on the properties of orally disintegrating tablets with the drugs domperidone and lisinopril The study deals with the influence of the type of co-processed dry binder on the compressibility of directly compressible tableting materials and the properties of orodispersible tablets containing the drugs domperidone and lisinopril. The tested co- processed dry binders are Ludiflash ® , Prosolv ® ODT G2 and Parteck ® ODT. The tablets further contain 1% sucralose as a sweetener and 1% magnesium stearate as a lubricant. The tablets are compressed by a compression force of 3 kN. The compressibility is evaluated by the energy profile of the compression process. Tensile strength, friability, wetting time, disintegration time, and porosity of tablets are tested. In the group of placebo, Parteck ® ODT showed the highest total energy of compression, whereas Prosolv ® ODT G2 showed the lowest values. The values of this energy decreased with the addition of drugs in all formulations, with domperidone having more significant effect....
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Dosing of veterinary eye drops 1
Marková, Jana ; Šklubalová, Zdeňka (advisor) ; Smékalová, Monika (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of: Pharmaceutical technology Consultant: doc. PharmDr. Zdeňka Šklubalová, Ph.D. Student: Jana Marková Title of Thesis: Dosing of veterinary eye drops 1. The main purpose of this thesis was to find out, whether and to what extent the rate of dispensing, the dispending angle (90ř, 65ř, 45ř) and the volume of preparation (30 ml, 15 ml, 5 ml) had effected the mass of commercial eye drops for poultry vaccination. Drops were produced manually by using conventional dispensing system (plastic 30 ml dropper bottle and dropper tip) and by using a new prototype of semi-automatic device. The drop mass increased with increasing the rate of drop formation in every examined combination of factors. With decreasing of the dispensing angle, the drop mass decreased only in a case of constant rate dropping. In all other cases, especially with volume reduction to 15 ml and 5 ml, the drop size often increased due to the wetting of hemispherical dropper tip. As a result, higher variability of drop masses had occurred. With using the semi-automated prototype, the preparation volume had no impact on the final drop mass. On the other hand, higher variability of doses was noted for studied suspension eye drops.
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Development of material for gelatin-based ultrasound brain phantom
Vaclaviková, Andrea ; Smékalová, Monika (advisor) ; Šklubalová, Zdeňka (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Technology Supervisor: Mgr. Monika Smékalová, Ph.D. Consultant: MUDr. Michael Bartoš Student: Andrea Vaclaviková Title od thesis: Development of material for gelatin-based ultrasound brain phantom There are more aspects that have an important role in selection of material for production of single-use ultrasound brain phantom: kind of material, acoustic property, price of materials and their accessibility, simplicity in preparation and its storage requirements, time stability and further. Gelatine as a hydrogel is a proper material for imitation of biological tissues since human body is mostly formed by water what is a prerequisite for acoustic and mechanical quality. Besides that, this natural biopolymer can be available for low costs. The goal was to find suitable combinations in proportion to gelatine, crosslinker, plasticiser, and preservatives in order to create material for ultrasound brain phantom with optimal time of solidification and similar acoustic property of brain in terminal stage. The emphasis was also put on temperature and microbiological stability requirements. For this purpose, there were arranged set of samples of 5%, 7,5% and 10% of gelatine with different proportion of...
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