Here below each project you can find the name of academic supervisor(s), his university/department and project assignments to research area(s) from five key domains in The Parc: Solid state chemistry, Preformulation and solid state analysis, Drug design and process, Biopharmacy and Preclinical in vivo testing. For more information on a specific Ph.D. project, you can contact us at info@theparc.eu or you can contact the academic supervisor directly (find email below each project description).
Do you have your own original research idea for a Ph.D. project which could fit into the scientific scope of The Parc? Do not hesitate to contact us at info@theparc.eu. We are searching for creative and talented students.
Further details about the program are provided on our Study page >
Join us in 2020!
Modeling of drug release from the solid dispersions by diffusion erosion models
This work is aimed at the study of the drug release from the solid dosage forms comprising solid dispersions. Such formulations exhibit a well-defined structure, and the drug dissolution can be studied not only by classical dissolution techniques, but also by the apparent intrinsic dissolution. Several fronts develop in dosage forms of this type, where those fronts correspond to the liquid penetration, drug leaching and erosion of the residual matrix. Such processes can be described by diffusion-erosion models, which allow determining their rate controlling steps and characteristic rates to be used for the design of controlled release drugs.
Supervisor prof. Ing. Petr Zámostný, Ph.D. (Petr.Zamostny@vscht.cz)
University University of Chemical Technology, Department of Organic Technology
Parc area Biopharmacy
Application of milling and co-milling processes to formulation of poorly soluble drugs
Poorly soluble drugs (II and IV classes of biopharmaceutical classification system) represent an important segment of marketed drugs. Improving solubility or at least the drug release kinetics is therefore a continuing challenge, which is approached by many ways on several levels. The milling, nano-milling, and/or co-milling processes of a drug with optional other excipients provide a way how to change the phase composition of the drug, increase the specific surface of drug particles, modify that surface, and also form composite particles. This study should be aimed at the options and possibilities of improving the drug release by all the above mechanisms, especially those related to particle technology. The study should involve both the preparation of particles and their formulation into suitable dosage forms and seek optimized approaches bringing the best performance while complying with the requirements of industrial manufacturability of the formulation.
Supervisor prof. Ing. Petr Zámostný, Ph.D. (Petr.Zamostny@vscht.cz)
University University of Chemical Technology, Department of Organic Technology
Parc area Drug Delivery and Design
Study of binary effects in process of particulate solid mixtures compaction
The topic is aimed at studying the structure effects of two or more component mixtures on the mixture behavior in compaction and tablet compression processes. The study will involve pairs of particulate materials, relevant for unit operations in solid dosage form production, such as filler-glidant, filler-lubricant, filler-binder, or interactive mixtures of carrier-API. The compaction characteristics of the mixtures will be studied using a compaction analyzer and evaluated in relation to properties of the mixture and its structure. The results should be further employed to develop co-processed excipient mixtures for a general application in direct tablet compression blends.
Supervisor prof. Ing. Petr Zámostný, Ph.D. (Petr.Zamostny@vscht.cz)
University University of Chemical Technology, Department of Organic Technology
Parc area Preformulation
Electrochemical oxidation for stress testing of API stability
The aim is to develop a methodology for stress testing of API stability using oxidation in an electrochemical flow cell instead of standard chemical oxidation using hydrogen peroxide solution. Electrochemical oxidation in the miniaturized flow cell promises significant savings thanks to shorter oxidation times as well as low consumption of material. However, the results obtained from electrochemical oxidation must be comparable to those obtained from standard chemical oxidation and search for appropriate conditions of electrochemical oxidation can thus be rather challenging.
Supervisor RNDr. Petr Kozlík, Ph.D. (kozlik@natur.cuni.cz)
University Charles University, Faculty of Science, Department of Analytical Chemistry
Parc area Preformulation
Capillary electrophoresis study of interactions between liposomes and selected compounds/nanoparticles
The aim is to develop a methodology that will allow us to study the interactions of selected compounds and nanoparticles with liposomes. This interaction mimics the interaction with the cell membrane and thus capillary electrophoresis can quickly and readily provide information concerning drug delivery and its behavior in the biological environment. Particles and compounds trapped inside a liposome will exhibit different electrophoretic mobility than free ones. This will enable the distinction of free analytes and analytes present inside liposomes.
Supervisor RNDr. Tomáš Křížek, Ph.D. (tomas.krizek@natur.cuni.cz)
University Charles University, Faculty of Science, Department of Analytical Chemistry
Parc area Preformulation, Biopharmacy
Stabilization and controlled release of a drug by coating of drug particles with polymers
Current active pharmaceutical ingredients (API) commonly have very low bioavailability, which is in most cases caused by their low water solubility. One of the possibility to improve this situation is to prepare metastable polymorphic forms, which are having intrinsically higher water solubility. However, this often results in their low chemical or physical stability, which limits their application. The main goal of this project is to investigate the possibility to coat surface of metastable API particles by suitable polymeric compound to generate protective layer. In addition, such layer might also provide other functionality, which is controlled release of API during dissolution. Therefore, student will be involved in the testing of various methods to coat API particles by various polymers. As promising method is milling as this method is commonly used for preparation of metastable forms of APIs followed by attachment of the polymer on the surface of metastable forms of API. Small-scale apparatus will be used to test various operating conditions as well as combination of API and various polymers. Prepared API particles coated with polymer will be consequently characterized by several techniques including SEM, XRD, DSC etc., combined with the measurement of API dissolution kinetics. Here time evolution of the API concentration in the used media together with size and morphology of particles will be followed by UV/VIS and Raman spectroscopy (both API concentration), FBRM (particle size) and optical video microscopy (particle size and shape). In the last stage of the project student will be responsible for the scale up of this process to illustrate possibility to prepare larger amount of coated API particles. Simulated impact of normal and tangential forces similar to those occurring during formulation, i.e. granulation and tableting, will provide information about the mechanical robustness of developed coating.
Supervisor prof. Ing. Miroslav Šoóš, PhD., Ing. Eliška Skořepová, Ph.D. (Miroslav.Soos@vscht.cz)
University University of Chemical Technology, Department of Chemical Engineering
Parc area Solid State Chemistry, Preformulation
Preparation of co-amorphous solid forms of drug substances
Low solubility of drugs represent significant drawback in development of new drug products. Possibility to improve this limitation is formulation of drug molecules in amorphous forms, e.g. using polymers formulated in hot-melt extrusion process, precipitation from solution or via spray drying. Despite significant improvement of drug dissolution characteristics, commonly there is a limited amount of drug, which can be solubilized within a polymeric matrix and thus prevent drug molecule to recrystallize. New approach to prepare amorphous drugs is to use small molecules, which can form co-amorphous solid forms. In this thesis, we will investigate possibility to prepare co-amorphous solid forms for selected drug molecules. Student will start with the screening process where various small molecule excipients will be tested using ball mill technique. Prepared solid forms will be characterized by XRD and DSC. For suitable candidates we will measure long-term stability under elevated temperature and humidity as well as measure their dissolution kinetics. In the last part of the project, student will be responsible for process scale-up and testing of process robustness.
Supervisor prof. Ing. Miroslav Šoóš, PhD., Ing. Eliška Skořepová, Ph.D. (Miroslav.Soos@vscht.cz)
University University of Chemical Technology, Department of Chemical Engineering
Parc area Solid state Chemistry, Preformulation, Biopharmacy
Controlling drug crystals properties during crystallization and their impact on consequent unit operations
Active Pharmaceutical Ingredients (APIs) are commonly small molecules, which are prepared by crystallization process. Properties of prepared crystals (i.e. physico-chemical but also formulation properties) are strongly dependent on the used drug solid form, their size and crystal morphology. Therefore, the focus of this project is to study impact of crystallization process parameters and post-processing step on the prepared drug crystals with respect to size, morphology and polymorphism. Temperature modulated batch crystallization will be combined with wet-milling process to control the shape as well as flow properties of prepared drug crystals. Crystallization step will be combined with following steps, i.e. filtration and drying, to evaluate the impact of the crystal size and shape on the efficiency of these unit operations. In parallel, we will also study impact of washing step on the amount of remaining solvent and the polymorphic stability of the final product. While pharmaceutical industry is typically using batch operation, as a part of this project we will investigate the possibility to prepare same drug crystals as studied in batch mode in a continuous process. Process analytical technology capable to measure crystal size, shape and morphology com will analysis of composition via Raman spectroscopy will be used to ensure constant product quality. On-line measurement will be supported by off-line measurement via SEM, IR spectroscopy, XRD and NMR. Student will be also involved in the scale up of developed process.
Supervisor prof. Ing. Miroslav Šoóš, PhD., Ing. Eliška Skořepová, Ph.D. (Miroslav.Soos@vscht.cz)
University University of Chemical Technology, Department of Chemical Engineering
Parc area Solid State Chemistry
Acidorezistant forms of prazols for more effective treatment of stomach ulcers
Prazols are a group of pharmaceutical compounds, which block the production of hydrochloric acid in the stomach through proton pump inhibition. They are the drug of first choice for the treatment of peptic ulcers and other gastrointestinal diseases. However, the molecules are unstable at low pH (such as in stomach), so now, they must be coated in an acidorezistant protective layer that only dissolves at the higher pH of the intestine. The goal of this work will be to prepare novel multicomponent solid forms of prazols with pH-controlled solubility. Through the preparation of salts, cocrystals, coamorphs and solid dispersions, we aim to create solid forms that will have lower solubility in acidic conditions than in basic ones, therefore negating the need for the acidorezistant coating. Samples will be prepared by crystallization or grinding. The properties of the prepared materials will be evaluated regarding purity, stability, crystallinity (XRPD, SEM, DSC, NMR) and pH-dependant solubility.
Supervisor prof. Ing. Miroslav Šoóš, PhD., Ing. Eliška Skořepová, Ph.D. (Miroslav.Soos@vscht.cz)
University University of Chemical Technology, Department of Chemical Engineering
Parc area Solid State Chemistry
Thin layers based on PLGA derivatives for topical administration of drugs
This topic deals to polymer layers based on the derivatives of PLGA, mainly brached, estimated for topical administration of drugs (antifungal). Formulation factors of the system composition such as the polymer type and concentration, plasticizer type and concentration, and solvent used on the properties of films will be studied as well as their influence on drug release. Methods: thermal (DSC) and rheological behaviour, dissolution tests in vitro, in vivo testing of antimicrobial activity and drug transport in tissue (nail, skin). The statistical methods of experiment design (DoE, PCA) will be used to optimize composition of layers.
Supervisor doc. PharmDr. Zdeňka Šklubalová, Ph.D. (sklubalova@faf.cuni.cz)
University Charles University, Faculty of Pharmacy, Department of Parmaceutical Technology
Parc area Preformulation, Biopharmacy
Flowability of pharmaceutical particulate materials and its mechanisms
The topic is focused on the flow, consolidation and compression properties of selected pharmaceutical materials, particularly, the excipients produces by spray drying. The aim is to study surface characteristics of particles influencing bond ability including the potential to form interactive mixtures and the process characteristics of binar mixtures. Methods: static and dynamic flow properties such as the angle of repose, consolidation dynamic, flow through orifice, avalanching, schear testing. Surface properties: BET, AFM, surface energy. Predictability of flow properties with the use of particle behaviour modeling in relationship to cohesivenes, linear fractal dimension and bulk fractal dimension of powder bed.
Supervisor doc. PharmDr. Zdeňka Šklubalová, Ph.D. (sklubalova@faf.cuni.cz)
University Charles University, Faculty of Pharmacy, Department of Parmaceutical Technology
Parc area Preformulation, Biopharmacy
Relationship between in vivo/in vitro pharmacokinetics and drug-induced gene expression alterations in animal models and cultivated cells
A discrepancy between in vivo and in vitro gene expression has been described. This could be explained by different drug disposition patterns in vitro and in vivo. Therefore, the presented postgraduate work will be focused on the investigation of influence of drug disposition in vivo and in vitro on time-dependent drug-induced gene expression alterations in animals and cultivated cells under physiological and pathological conditions. For these purposes, pharmacokinetics and the therapeutic potential of promising cytoprotective agents in preclinical models of inflammatory diseases, e.g. non-alcoholic liver disease and steatohepatitis, obesity, experimental rheumatoid arthritis, experimental autoimmune encephalomyelitis atc., will be tested. The influence of pharmacokinetics on the pharmacological effects of promising drugs will be evaluated by gene expression of important cell signalling regulatory biomolecules compared to the severity of disease or cell survival/viability and parameters of inflammation and oxidative stress both in vivo (in laboratory animals) and in vitro (in cell cultures) with their subsequent mutual comparison. The results of this work should help to design a suitable preclinical pharmacological model for the study of potentially cytoprotective agents and to optimize their dosing and thus safety.
Supervisor MUDr. Nikolina Kutinová Canová, Ph.D. (Nikolina.Canova@lf1.cuni.cz)
University Charles University, First Faculty of Medicine, Institute of Pharmacology
Parc area Preclinical in-vivo testing
Robotic compounding line for continuous manufacturing of personalised formulations
Currently, approximately 10 % of the whole population and 30 % of adults aged 65+ take five or more different prescription medications each day. Low prescription compliance due to the complexity of the prescription regime is a major problem, responsible for an estimated 125,000 deaths per year and 10 % of all hospitalizations in the USA alone. Therefore, it would be beneficial if each patient could take only 1 pill per day that would contain the required drug combination while being bioequivalent with the single-drug dosage forms. The aim of this project is to design and assemble an automatic manufacturing line that would enable the production of patient-specific batches based on their electronic prescription for a given period of time, e.g. 30 days. The line will be based on the well-established process of pharmaceutical compounding. However, instead of manual compounding by a live person, this process will be autonomous and rely on robotics. The project will involve the selection and validation of individual compounding sub-stations and their connection to a fully automatic bench-scale manufacturing line. This project would best suit a person with a background in engineering (chemical, mechanical, electrical).
Supervisor prof. Ing. František Štěpánek, Ph.D. (Frantisek.Stepanek@vscht.cz)
University University of Chemical Technology, Department of Chemical Engineering
Parc area Drug delivery and design
Programmable drug release from multi-unit pellet systems
Multi-unit pellet systems (MUPS) are dosage forms composed of smaller sub-units, typically pellets or mini-tablets, combined into a single larger tablet or capsule. Traditionally, the sub-units are all identical. However, by mixing sub-units of different properties such as particle size, disintegration rate, composition, or coating thickness, it is theoretically possible to fine-tune the drug release from the MUPS almost arbitrarily. The aim of this project is to explore the possibility to achieve precise control over drug release from MUPS by programmed mixing of different grades of sub-units. The project will involve the formulation of individual sub-units for a selected set of drugs, their production by fluid-bed coating or multi-tip tablet compression, their individual characterization and finally their controlled combination into MUPS with a pre-defined release profile. The project will suit a person with a background in pharmaceutical sciences or chemical engineering.
Supervisor prof. Ing. František Štěpánek, Ph.D. (Frantisek.Stepanek@vscht.cz)
University University of Chemical Technology, Department of Chemical Engineering
Parc area Drug delivery and design
Novel drug delivery systems for steroid-based drugs
Steroids represent a promising class of drugs for a range of diseases including chronic pain and various neurological disorders. However, many potentially promising lead structures suffer from poor aqueous solubility, which complicates their pre-clinical evaluation. The use of incompatible formulations such as DMSO solutions at the cell culture level, o/w emulsions for parenteral administration during small animal studies, and solid dosage forms for oral administration at the stage of larger animal studies, complicates the understanding and correct translation of results. The aim of this project is to come up with a common formulation platform that would be applicable for pre-clinical testing at all stages. The project will involve the comparison of several formulation approaches, namely liposomes, lipid-coated nanocrystals, mini-emulsions, and impregnation to porous micro- or nano-particles. The feasibility of these formulation platforms will be compared both in vitro and in vivo using several drug substances from the steroid family, both currently known and newly discovered. This project will suit a person with background in chemistry or pharmacy.
Supervisors prof. Ing. František Štěpánek, Ph.D. (Frantisek.Stepanek@vscht.cz), Eva Kudová, Ph.D. (Eva.Kudova@uochb.cas.cz)
University University of Chemical Technology, Department of Chemical Engineering; Institute of Organic chemistry and biochemistry
Parc area Drug delivery and design, Biopharmacy
Combined dissolution and permeation platform for the screening of formulation prototypes
Supersaturating drug delivery systems such as amorphous solid dispersions or amorphous drugs loaded to mesoporous carriers can significantly increase the dissolution rate of poorly soluble APIs. However, in order to translate this into increased bioavailability, the API must be absorbed from the GI tract. The aim of this project is to develop methodology for the simultaneous measurement of dissolution and permeation under biorelevant conditions, and so enable early-stage evaluation of formulation prototypes that minimized false positives as well as false negatives. Permeation methods based on model lipid layers, cell cultures and co-cultures, and hollow fibre based modules will be compared and their predictions compared from the results of in vivo studies for several chosen molecules from the BCS class II and class IV category.
Supervisors prof. Ing. František Štěpánek, Ph.D. (Frantisek.Stepanek@vscht.cz), prof. G. E. Flaten
University University of Chemical Technology, Department of Chemical Engineering; University of Tromso
Parc area Biopharmacy
Advanced formulation approaches for topical delivery
Although skin appears to be a macroscopically homogeneous and biologically passive structure, it is exactly the opposite: it is incredibly heterogeneous both chemically and structurally, and it is host to a diversity of active cells such as macrophages and bacteria. Traditional approaches to topical delivery have relied on relatively simple systems such as passive diffusion from water- or oil-based solutions or creams/gels. The aim of this project is to investigate bioactive transport as a mechanism for topical delivery and find a solution to such molecules as therapeutic peptides, which are known to be extremely challenging to formulate and delivery to the body. This project will explore the use of drug delivery systems that are actively phagocytised for targeting macrophages residing in the skin. These drug delivery systems will include naturally sourced polysaccharide shells or lipidic vesicles obtained from single-cell organisms. Their mild immunogenicity, biocompatibility and ability to encapsulate a broad range of molecules will be utilized for the formulation of APIs that have proven to be challenging by traditional means.
Supervisors prof. Ing. František Štěpánek, Ph.D. (Frantisek.Stepanek@vscht.cz), doc. Mgr. Jarmila Zbytovská, Dr. rer.nat. (Jarmila.Zbytovska@vscht.cz)
University University of Chemical Technology, Department of Chemical Engineering and Department of Organic Technology
Parc area Drug delivery and design, Biopharmacy
Oleogels for drug delivery
Oleogels, like hydrogels, are semi-solid materials that can contain up to 99 % of a liquid, which is solidified by a three-dimensional polymer network. While hydrogels contain as the liquid and the polymers are hydrophilic, oleogels contain oil and an oleophilic polymer network. Many APIs that are poorly soluble in water could potentially be formulated using oleogels and be either directly dissolved in the oil phase or form a particle depot that would dissolve in the oil gradually and act as a longer-lasting reservoir. The aim of this project is to evaluate the suitablitity of selected oleogel formulations for drug delivery applications from the point of view of manufacturability, drug release kinetics, drug stability, and biological compatibility. The application of oleogels will be demonstrated using several selected APIs both in vitro and in vivo.
Supervisors prof. Ing. František Štěpánek, Ph.D. (Frantisek.Stepanek@vscht.cz), RNDr. Ivan Řehoř, Ph.D. (Ivan.Rehor@vscht.cz)
University University of Chemical Technology, Department of Chemical Engineering and Department of Organic Technology
Parc area Drug delivery and design
March 18. 2020