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Study of flow and consolidation behaviour of binar mixtures of Cellets and filler for preparation of multilayer tablets
Jarolímová, Žofie ; Šklubalová, Zdeňka (advisor) ; Franc, Aleš (referee) ; Zámostný, Petr (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Technology Candidate Mgr. Žofie Jarolímová Supervisor doc. PharmDr. Zdeňka Šklubalová, Ph.D. Title of Doctoral Thesis Study of flow and consolidation behaviour of binary mixtures of Cellets and filler for preparation of multilayer tablets The manufacture and quality of solid dosage forms is influenced mainly by flow, consolidation and compaction properties of powder excipients. In this work, the behaviour of pellets made of microcrystalline cellulose (cellets), which might be used as a drug carrier in multilayer tablets, and their binary mixtures with microcrystalline cellulose was studied. More than 20 powder excipients commonly used in tablet production and their binary mixtures were involved in preliminary studies. Measuring of the angle of repose, Hausner ratio and the mass flow rate through a hopper orifice was influenced by the particle shape, size and the width of the particle size distribution. In order to identify easily the free flowing substances, the hopper orifice having 10 mm diameter was useful. Excellent flow properties were confirmed for cellets with conventional testing methods thanks to their spherical shape and narrow particle size distribution. The avalanche testing using a rotational drum...
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Formulation of freeze dried tablets for buccal application of vaccines
Vuová, Ngoc Lien ; Šklubalová, Zdeňka (advisor) ; Holas, Ondřej (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of: Pharmaceutical Technology Mentor: Doc. PharmDr. Zdeňka Šklubalová, Ph.D. Student: Ngoc Lien Vuová Title of Thesis: Formulation of freeze dried tablets for buccal application of vaccines Mucosal vaccines represent an attractive way of vaccination with an advantage of inducing both systemic and local immunity. The aim of this diploma thesis was designing a composition of freeze-dried tablets for buccal administration of a model Bordetella pertusis vaccine. The easy removal from blister, firmness and aesthetic appearance as well as the appropriate taste and mucoadhesivity were the required product quality parameters. The excipients were characterised by differential scanning calorimetry, osmolality and pH measurement; the mechanical properties and disintegration time of freeze-dried tablets were evaluated. Among the variety of studied excipients and their combinations, dextran 40 as the main component of the preparation provided the best results. For the further modification of properties, the addition of fish gelatin, iota carrageenan and macrogol 300 is suitable. Freeze-dried tablets containing trehalose, mannitol and povidon 25 did not achieve the desirable quality parameters. Freeze- dried tablets containing iota carrageenan...
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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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Influence of mixing conditions of microcrystalline celluloses with lubricants on compression process and tablet strength.
Kučerová, 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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Study of influence of a hydrophilic carrier on the dissolution rate of the BCS II drug
Bunes, Andrea Suther ; Šklubalová, Zdeňka (advisor) ; Vraníková, Barbora (referee)
Charles University, Faculty of Pharmacy in Hradci Králové Department of: Pharmaceutical Technology Supervisor: Assoc. Prof. PharmDr. Zdenka Šklubalová, Ph.D. Consultant: Mgr. Jana Brokešová Student: Andrea Suther Bunes Title of Thesis: Study of influence of hydrophilic carriers on the dissolution rate of a BCS II drug The aim of this thesis was to study the effect of mixing and co-milling with hydrophilic carriers on the dissolution rate of a model BCS II drug meloxicam. The mixtures of two different drug loads (1-1, 1-8) were characterized for granulometric and dissolution parameters. USP-4 apparatus assembled with a flow-through powder cell (an open loop) was used to estimate meloxicam relative dissolution rate rrel (min-1 ). Mixing with lactose, particularly in a higher ratio, increased the relative dissolution rate in comparison to the pure meloxicam. The effect was further increased by co-milling, but an unfavourable event of agglomeration occurred, especially for the 1-1 drug-excipient ratio sample. Adding chitosan solved this problem due to the formation of interactive mixture. The co-milled sample containing chitosan and lactose in a 1-8 ratio showed the highest rrel = 0.48 min-1 .
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Adhesive properties of thin layers based on plasticized polyesters
Soukupová, Jana ; Šnejdrová, Eva (advisor) ; Šklubalová, Zdeňka (referee)
CHARLES UNIVERSITY Faculty of Pharmacy in Hradec Kralove Department of Pharmaceutical Technology Name: Jana Soukupova Title of diploma thesis: Adhesive properties of thin layers based on plasticized polyesters Supervisor: PharmDr. Eva Snejdrova, Ph.D. This diploma thesis deals with rheological, adhesive and dissolution properties of thin layers based on the branched polyester of D,L- lactic acid and glycolic acid, plasticized with methyl- salicylate, and loaded with salicylic acid. The theoretical section describes bioadhesion, its mechanism and theories, in vitro adhesive tests focused mainly on the method of rheological synergism, tensile and "wash off" tests. In the experimental section, the flow properties of plasticized polyesters, hydrated mucin from porcin stomach, and their mixtures were studied using absolute rotational rheometer. The analysis of the viscosity curves revealed that plasticized polyesters are Newtonian systems, mucin and its mixtures with polymer have pseudoplastic behaviour. Adhesive properties of the thin layers were established by equation of rheological synergism based on viscosity of polymer, mucin and their mixtures measured at shear rate of 10 s-1 . The adhesive properties of thin layers were also determined using tensile test on rheometer, and evaluated as the...
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Study of excipients' influence on the drug dissolution from tablets
Ouzký, Miroslav ; Šklubalová, Zdeňka (advisor) ; Mužíková, Jitka (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of: Pharmaceutical Technology Supervisor: Consultants: Assoc. Prof. PharmDr. Zdeňka Šklubalová, Ph.D. Mgr. Jana Brokešová, Mgr. Daniel Pěček Student: Miroslav Ouzký Title of Thesis: Study of excipientsʼ influence on the drug dissolution from tablets The aim of this work was to study the influence of excipients on the dissolution of the high-dose active substance from tablets. The tablets were compressed from the granules prepared by wet-granulation method. 11 batches of tablets which contained two different fillers: either lactose or microcrystalline cellulose, respectively; and extragranularly added disintegrant: either croscarmellose or crospovidone, respectively, in three concentration levels of 2 %, 3,7 % or 5,4 % were prepared. Tablets were packed into aluminium/PVC blisters. The paddle dissolution test was used to determine the release of the active substance into phospate buffer pH 7,2 at the time of preparation (time 0) and at the time points 1.5, 3 and 6 months of stability assay at 40 řC and 75 % relative air humidity. The results show that the drug release from tablets containing microcrystalline celulose was generally faster than from those containing lactose. The same was true for tablets to which croscarmellose was...
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Study of flow and consolidation behaviour of pharmaceutical free-flowable excipients
Janoutová, Hana ; Šklubalová, Zdeňka (advisor) ; Vraníková, Barbora (referee)
Charles University, Faculty of Pharmacy in Hradci Králové Department of: Pharmaceutical Technology Consultant: doc. PharmDr. Zdeňka Šklubalová, Ph.D. Student: Mgr. Hana Janoutová Title of Thesis: Study of flow and consolidation behaviour of pharmaceutical free-flowable excipients Flowability is an important characteristic of pharmaceutical powders that affects processing of the powder. Flow and granulometric properties of mannitol (Pearlitol® 200 SD, Pearlitol® 400 DC) and xylitol (Xylisorb® XTAB 240, Xylisorb® XTAB 400) were evaluated in this thesis. The angle of repose was measured by an automatic tester Erweka and a prototype complying with ASTM standards for the determination of angle of repose. Hopper orifices having a diameter 6 mm, 8 mm, 10 mm, 12 mm, and 15 mm were used to study the influence of the orifice diameter on the value of angle of repose. Determination of angle of repose was completed with the measurement of density of a formed pile. The values of angle of repose measured by the Erweka tester were higher in all samples than those obtained from the prototype. For both apparatuses, the angle of repose decreased with increasing in the orifice diameter.
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Formulation of freeze dried tablets for oromucosal administration of peptides
Macáková, Eliška ; Šklubalová, Zdeňka (advisor) ; Holas, Ondřej (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of: Pharmaceutical Technology Consultant: Doc. PharmDr. Zdeňka Šklubalová, Ph.D. Student: Eliška Macáková Title of Thesis: Formulation of freeze dried tablets for oromucosal administration of peptides Freeze-drying is one out of the important methods for stabilization of active substances, particularly peptides, in pharmacy. The formulation of freeze-dried buccal/sublingual tablets for administration of peptides into the oral cavity is the main target of this thesis. The aim is to propose the combination of appropriate excipients and their concentration to achieve the suitable organoleptic properties and disintegration time of the product cake. The measurement of pH, osmolality, the thermal properties of substances, as well as the evaluation of mechanical quality of tablets and their disintegration were used. In conclusion, the combination of excipients for the composition of matrix for the futher development.
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Rheological behaviour of mixtures for freeze-drying
Vavřich, Dominik ; Šnejdrová, Eva (advisor) ; Šklubalová, Zdeňka (referee)
CHARLES UNIVERSITY Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Technology Name of author: Dominik Vavřich Title of diploma thesis: Rheological behaviour of mixtures for freeze-drying Supervisor: PharmDr. Eva Šnejdrová, Ph.D. The diploma thesis deals with the evaluation of rheological properties of aqueous dispersions of fish gelatin and carrageenans intended for lyophilization. Theoretical part of this work is dedicated to the characterization of fish gelatin and carrageenans which were used for preparation of the mixtures in experimental part of this work. Characterization of an oral cavity from an application of medicaments point of view and an orally disintegrating tablets of the medicine with a focus on the lyophilized tablets are also presented. Mixtures of the fish gelatin and the carrageenans were prepared in the experimental part of the work. Their rheological behaviour employing an absolute rotational rheometer Kinexus Pro+ was measured and evaluated. Also, the testing of the rheological characteristics of these materials transformed into the freeze-dried tablets was performed. Nonlinear viscous curves were obtained, and they were mathematically evaluated by the Power law model. Pseudoplastic behaviour of the mixtures can be derived from the results of acquired...
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