| STAFF | EDUCATION | RESEARCH AND DEVELOPMENT | LABORATORIES | COOPERATION PARTNERS |
The Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Debrecen is located in Debrecen, in the second biggest town of Hungary. The University of Debrecen has great traditions in high-quality research and education and the Faculty of Pharmacy is committed to follow the mission of the University. The Department of Pharmaceutical Technology was established in 1996 and since then the progress of the institute is continuous.
Contact us:
H-4032 Debrecen, Nagyerdei krt. 98.
Tel/fax: +3652/411-717/54023
email: gytk@pharm.unideb.hu
In education, both Hungarian and English language programs are available for pharmacy students and the number of ERASMUS-supported students is growing every year. Our lecturers are internationally respected professionals and active researchers. Besides high-level theoretical education, the practical training has also an important role. The laboratories are well-equipped with the highest level of instruments. The practice oriented pharmaceutical industrial lab is unique compared to similar Hungarian pharmaceutical training centers. Our students receive training in compounding pharmacy and also in pilot and industrial-scale drug manufacturing. The Department is responsible for several courses related to pharmaceutical technology or supervise pharmaceutical subjects.
COURSES:
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- Obligatory courses
- Pharmaceutical Technology Theory I.
- Pharmaceutical Technology Theory II.
- Pharmaceutical Technology Theory III.
- Pharmaceutical Technology Theory IV.
- Pharmaceutical Technology practice I. (Prescription Writing I.)
- Pharmaceutical Technology practice II. (Industrial practice I.)
- Pharmaceutical Technology practice II. (Prescription Writing II.)
- Pharmaceutical Technology practice III. (Industrial practice II.)
- Pharmaceutical Technology practice III. (Prescription Writing III.)
- Pharmaceutical Technology practice IV. (Industrial practice III.)
- Industrial Pharmaceutical Technology
- Pharmacy Propedeutics
- Pharmaceutical Communication Skills
- Drug Interactions Theory
- Elective courses
- Galenic Preparations
- Industrial Pharmaceutical Practice
- Biocosmetics
- Nanopharmaceutics
- Nutritional Therapy
- Introduction to Scientific Research
- Pharmaceutical Computer Administration
- Juristic Knowledge for Pharmacists
- Veterinary Hygiene
- Optional courses
- Research methodology in Pharmacy
- Selected innovative research in Europe
- Biochemistry catching up course
- Obligatory courses
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RESEARCH AND DEVELOPMENT
The research profile of the Department focuses on the formulation and characterization of novel, innovative pharmaceutical dosage forms and their excipients. Oral solid formulations, topical formulations, 3D-printing, microparticles, nanoparticles and liposomes, micro-, and nanoemulsions are the most studied drug carriers in the Department. We have special interest on surface active agents and cyclodextrins which have solubility increasing and absorption enhancing effects. The Department has all of the facilities, which are required for the physicochemical and biological characterization of the above mentioned drug delivery systems. In the cell culture laboratory several types of cell lines and in vitro barrier models are available to perform biocompatibility and bioavailability studies. Our students interested in research can participate in several research activities in the frame of Student Scientific Research Association. Special pharmaceutical research topics may be selected and high-level thesis may be written at this Department. The Department of Pharmaceutical Technology as the part of an internationally active pharmaceutical faculty is engaged in collaborative projects and partnerships all over Europe. Among our cooperation in the field of pharmaceutical research, universities, small and medium enterprises and big pharmaceutical companies can be found.
PUBLICATION LIST
COOPERATION PARTNERS
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Universities |
Organizations |
Companies |
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Department of Pharmaceutical Technology, University of Szeged (Szeged, Hungary) |
Pharmaceutical Chamber of Hungary |
Teva Pharmaceutical Industries (Debrecen, Hungary) |
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Institute of Pharmaceutical Technology, Semmelweis University (Budapest, Hungary) |
Hungarian National Committee of Pharmaceutical Care |
Richter Gedeon Plc. (Budapest, Hungary) |
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Department of Pharmaceutical Technology, University of Pécs (Pécs, Hungary) |
Hungarian Society of Pharmaceutical Sciences |
CycloLab (Cyclodextrin Research and Development Laboratory) (Budapest,Hungary) |
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Szent István University (Gödöllő, Hungary) |
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Gattefossé Chemical Company (Lyon,France) |
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Vasile Goldis Western University of Arad (Arad, Romania) |
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Meditop Pharmaceutical Ltd. (Pilisborosjenő, Hungary) |
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Claude Bernard University Lyon 1 (Lyon, France) |
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BASF (Mannheim, Germany) |
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Biological Research Centre, Institute of Biophysics, Eötvös Loránd Research Network (Szeged, Hungary) |
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Fempharma Ltd. (Debrecen, Hungary) |
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Cranfield Defence and Security, Cranfield University (Shrivenham, Swindon, UK) |
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VitalWEB Plus Kft. (Budapest, Hungary) |
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Technical University of Lisbon (Lisbon, Portugal) |
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VitaPlus Kft (Budapest, Hungary) |
The Department has dedicated laboratories for practical education at different levels of pharmaceutical technology and research laboratories for basic research and innovative developments. The pharmaceutical technology labs are suitable for formulation and scale-up studies especially in the field of solid dosage forms.
COMPOUNDING LABORATORY
This is the place of practical training for pharmacy students where they can gain practical skills and experience in the laboratory work of a pharmacy. During the three semester long training of the Prescription Writing Practice course all the main dosage forms and also the mostly used active substances and excipients are reviewed.
PILOT SCALE LABORATORIES
These labs have important role in the education, but also in the development of different pilot scale products. Three main areas covered here: solid dosage forms, semi-solid (galenic) formulations and sterile liquid formulations. Students can learn here the basics of aseptic manufacturing. A well-equipped laboratory is available here to produce and test granules, tablets and hard capsules. Ointments and other semisolid formulations can be prepared here in pilot-scale. Main equipment of these labs: a rotary tablet press, a semi-automated capsule filler, a lab-scale fluidized bed-mixer, a high shear granulator, a twin-screw extruder, dissolution tester, hardness tester, friability tester, sieve analyzer, a climate chamber, an ultra-centrifugal mill, a planetary ball mill, a texture analyzer, a Franz-diffusion cell, a laminar air flow box, and an autoclave. For drying processes two types of freeze-drying equipment and even a nanospray dryer can be used.
INDUSTRIAL-SCALE LABORATORY
These modern laboratories provide potential to demonstrate the technological challenges of industrial tablet and hard capsule manufacturing. A blister packaging machine is also available here for training pharmacy students. These labs are also suitable for product development when scaling up is necessary.
A well-equipped cell culturing laboratory is operating in the Department. Particularly different drugs, excipients (e.g. surfactants and preservatives) or drug carrier systems are tested here in consideration of their toxicity and bioavailability. Our researchers have many years’ experience with an in vitro human gastrointestinal barrier (Caco-2 and VB-Caco-2) model and HeLa human cervical cell line, but human blood-brain barrier model (hCMEC/D3) and human keratinocytes (HaCaT) are also used. In addition to monocultures, we constantly develop co-cultures that are primarily suitable for modelling inflammatory processes and barriers (HaCaT/THP-1, Caco-2/THP-1).
For biocompatibility testing real-time cell analysis (RTCA) system and the more traditional MTT assay are used. In vitro cell transport models were installed to compare the bioavailability of drugs or different formulations.
Many interesting experiments can be performed by flow cytometry. One of the main topics is to test different cyclodextrin derivatives as drug carrier systems. Moreover, a well applicable method is used to demonstrate antiinflammatory effect on Caco-2 cells and different tight junction proteins can be labeled and visualized by the fluorescent microscope.
R&D LABORATORY
Development of innovative pharmaceutical dosage forms is a really important research field of the Department. The range is really wide: liposomes, SMEDDS and SNEDDS, topical preparations with natural compounds, matrix tablets, extended release hard gelatin capsules (solid foams), 3D printable individual dosage forms, cyclodextrins and their polymers as drug carrier systems and formulation of probiotic containing microcapsules are just the main topics.
Interesting equipments and methods
The mid-sized ‘S 370’ type tablet press machine is a fully electronically controlled, modular-structured device. This construction facilitates the replacement of accessories and the cleaning steps between different products. Compression parameters can be set quickly and the process can be monitored by a touch-screen. This machine is suitable for development and also for industrial-scale manufacturing purposes (maximal capacity is 240,000 tablets per hour).
‘Planeta’ is a continuous motion capsule-filling machine with a filling capacity of 25,000 capsules per hour. The modular design means flexibility and ease of use. The product range is wide: powders, pellets, microtablets and even liquids can be filled into the hard-shell capsules. This mid-sized equipment is ideal for development and production of smaller batches.
The ‘NBP 950 S’ type blister packaging machine is suitable for wide range of products (solid dosage forms). It is ideal when frequent product and format changes are needed. Different blister layouts are available and most types of thermoplastic blister foils can be used. Maximal productivity is 400 blister per minute.
Spray drying is a gentle method for producing powders of specified particle size from solutions, emulsions, suspensions. With the new technological developments, nanospray dryer has a particle size in nanometer range, production yield is up to ~90%, while a sample volume of 1ml is sufficient. The nanospray drying technique is widely spread in the pharmaceutical industry, as it increases the stability and shelf life of the product due to its low moisture content. As a result of the structural changes poor water solubility can be improved, thus bioavailability can be increased. With the instrument nanoparticles, nanoemulsions, nanosuspensions can be formulated and modified drug release can be achieved. Toxicity of certain substances may be reduced and the selectivity of the active substance in certain organs may be increased, thus side effects may be reduced by nanospray drying technique. The drying process is gentle, thus stability and activity of heat-sensitive substances (proteins, peptides, amino acids, hormones) is maintained. At our department improving bioavailability and developing nasal drug delivery systems of different substances is a current project of ours.
Guava easyCyte™ 6HT-2L flow-cytometer has two lasers (488 nm, 642 nm), a forward-scatter, (FSC), a side-scatter (SSC), and four emission detectors (525/30, 583/26 nm, 695/50 and 664/20 nm). Samples are handled by an automated sampling system. Single cell analysis is performed by the instrument on cell suspensions. Typical applications: cell-viability measurements, detection of proteins on cell surface by immunolabeling, cellular uptake of fluorescent molecules, detection of the function of cellular organelles (e.g.: lysosomes).
Several methods are used in the pharmaceutics for liposome preparation. The phospholipid bilayer envelopes the drug molecules in the inner space of the liposome. Size and shape changes can be widely tailored to provide optimal and complex properites, such as circulation time, elasticity or triggered release. The LiposoFast LF-50 is a simple and robust instrument for the extrusion of lipid particles, liposomes. The extrusion is carried out while forcing the lipid dispersion through a membrane with known and fixed pore size, high pressure gas (nitrogen, air or other) should be used. This process can be used to produce unilamellar liposomes with homogenous size distribution. The capacity of the jacketed vessel is 50 ml, the extrusion chamber can be loaded with membranes of varous pore sizes (50 nm to 200 nm).
Within the framework of the Proof of Concept, the department has developed and built the innovative prototype of Quickfoamcell with Quick 2000 Ltd., as a corporation partner, in recent years. The developed technology was patent protected by the Department, it is able to continuously produce low-density, high porosity, solid foam matrix systems, which are suitable for gastro-retention. For most drugs with poor bioavailability, the GR system is a potential way to prolong effective plasma levels by administering lower doses of active substances. (patent link)
One of the research areas of the Department of Pharmaceutical Technology is the investigation of the antioxidant and other effects of various active ingredients (herbal and synthetic) after UV radiation. The Oriel Sol-UV solar simulator is able to emit a specific UV wavelength (UV-A or UV-B) evenly. The device is suitable for performing various photobiological experiments in vivo and in vitro (eg factor number determination, photo-toxicity test, photo-allergy test, photo-carcinogenicity test, photo-genotoxicity test, etc.). The lamp has a power of 1600 W, which is required to provide the so-called <5% “non-uniformity” value for a relatively large beam size on the entire workspace. In addition, for some samples, it is essential to use the highest possible illumination intensity to elicit a photographic response. Of course, the output power of the lamp can be varied between 10-100%, so it is also suitable for use with more sensitive samples.
3D printing is one of the most innovative manufacturing process for the development of different drug delivery systems. This layer-by-layer process enables fast and cheap manufacturing for the preparation of personalized medications. In our laboratory a Craftbot 3. fused deposition modelling 3D printer is available, with the method different drug delivery systems e.g. tablets, capsules, intravaginal rings, transdermal delivery systems or even microneedles can be manufactured from different polymeric materials. In our researches we use PLA, antibacterial PLA, PET, PETG, PMMA, TPU polymers and different modified, unique polymers as well.
In vivo biocompatiblity investigations with Galleria mellonella larvae
The larva of the greater wax moth is an increasingly popular model organism in the last two decades. Its primarily used as a host for various pathogens in order to differentiate their strains based on their virulence. The innate immune response of larvae is much similar to that of vertebrates (phagocytosis, complement system etc.). Also they are used for testing antimicrobial agents, to model their action in vivo. Such experiments lead to the involvement of the larva in toxicity experiments, where it was revealed, that the relative tolerance (mortality) of the specimens show high correlation with traditional rodent models. As no ethical approval is needed for their use, they offer a convenient, cheap and fast method, for the more precise prediction of toxicity in further animal experiments and the comparative toxicity of chemicals and mixtures. Our Department regularly carries out survivability tests of G. mellonella, where different new pharmaceutical formulations and/or excipients are injected individually into the specimens. The survivability is followed up for multiple days and the different test groups (usually n≥8) are statistically compared. The treated groups are composed of ≥8 specimens to enable correct analysis. Aqueous solutions, emulsions, fine suspensions can be injected, however, some chemicals, like ethanol or other organic solvents are extremely toxic.
The Encapsulator B-395 Pro is a semi-automated instrument used for the polymer encapsulation of chemical substances, bio-molecules, drugs, flavor and fragrances, pigments, extracts, cells and microorganisms under sterile and non-sterile conditions. The bead formation is based on the fact that a controlled, laminar liquid jet is broken into equally sized beads, if vibrated at an optimal frequency. They are then hardened by means of chemical or physical processes. The instrument provides just such controlled conditions to generate beads between 0.15 to 2 mm. It is ideally suited to encapsulate particles < 50 µm. One of the research fields in our Department is to enhance oral bioavailability of peptides. The encapsulation of peptides into finely divided bioadhesive polymer carrier systems is a preferable and widespread method to improve oral bioavailability due to their beneficial properties. Natural polymers are biosafe and highly inert carrier matrices as they not only protect the drug from gastrointestinal degradation but also improve absorption. With the help of Encapsulator B-395 Pro our research group have successfully formulated peptide-loaded calcium cross-linked alginate beads in order to protect the model peptide.
Our lab was equipped with an HPLC system (Merck-Hitachi ELITE) with photodiode array detector and automatic sample injection. The device supports the performance of preformulation assays, including logD determination, measurement of drug content and dissolution rate, measurement of cell permeability, and last but not least, measurement of biological samples. Our department has already acquired sufficient expertise in various sample processing before measurements such as liquid-liquid extraction or SPE. The equipment has been used in a number of our previous experiments, where plant active ingredients, preservatives, synthesized or marketed active ingredients were measured.
With the Zetasizer Nano ZS instrument three parameters can be measured: particle size, zeta- potential and molecular weight. These parameters are fundamental to characterize a complex. With this we measure the size and the zeta-potential of various complexes, such like different cyclodextrin-based complexes. Moreover, with this instrument we can determine the electrophoretic mobility of the different complexes.
Fourier transform infrared spectrometer (FTIR) is based on infrared spectroscopy. It has high precision, accuracy, speed, enhanced sensitivity, ease of operation, and sample nondestructiveness. The fundamental of infrared spectroscopic technology is on atomic vibrations of a molecule that only absorbs specific frequencies and energies of infrared radiation. The molecules could be detected and classified by FTIR because different molecules will have different infrared spectrum. The FT/IR-4600 is a powerful Mid-IR FTIR research grade spectrometer (wavenumber range 7800 to 350 cm-1). It has many features, such as non-hygroscopic KRS-5 windows to prevent damage to the interferometer, a Peltier stabilized DLaTGS detector and a high output ceramic source for maximum sensitivity. Permanent optical alignment is guaranteed by corner cube (retro-reflective) mirrors with auto-alignment for maximum energy. With a resolution of 0.7cm-1 and a S/N greater than 25,000:1.
Hot-melt extrusion is a robust, novel technique to make different pharmaceutical products. First, different polymeric filaments can be manufactured from polymeric granules mixed with different excipients and APIs. For the manufacturing a conveyor and a winding machine is available. Secondly, the machine is adequate for the manufacturing of granules and spheronization as well. Furthermore, solid dispersions can be manufactured in order to provide improved bioavailability.
The Retsch PM100 planetary ball mill is a suitable tool for grinding solid materials like dried herbal parts and dry extracts in the colloid size range, or to complex them with different complexing agents, for the enhancement of solubility, stability and bioavailability.