Here we bring the topics overview. Below the overview there are annotations and names of academic supervisor(s), their 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 2022!
____________________________________
PhD topics overview
01/ Controlling drug crystals properties during crystallization and their impact on consequent unit operations
02/ Correlation between hardness of multicomponent solid forms and disintegration capability of pressed tablets
03/ Continuous preparation of coamorphous forms of drugs and their characterization during dissolution
04/ Preparation of multicomponent solid forms of cannabinoids
05/ Massively paralel screening of pharmaceutical nanocomposites formed by spray drying from mixed solvents
06/ Collaborative robots in pharmaceutical formulation development
07/ Experimental and theoretical investigation of continuous powder blending and trituration
08/ Formulation strategies for API-independent drug release
09/ 3D printing of biological barriers for ex-vivo drug permeation studies
10/ Surface energy heterogeneity of particulate matter
11/ Monitoring and prediction of tablet disintegration behavior using texture analysis
12/ Stability of interactive mixtures and their utilization for drug delivery
13/ Design and optimization of unit operations for continuous manufacturing of solid dosage forms
14/ Modeling of drug release from the solid dispersions by diffusion erosion models
15/ Development of nanoparticulate formulations for targeting skin cancer
16/ Application of electrochemical oxidation in the study of stability and degradation of pharmaceutical substances
17/ Testing of lymphatic drug absorption
18/ Preclinical in-vivo testing of pharmacokinetics
19/ Development of Lymphatic Transport-Targeting Prodrugs
____________________________________
1/ 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 will be used for analysis of composition via Raman spectroscopy 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, Ph.D. (Miroslav.Soos@vscht.cz)
University University of Chemistry and Technology, Department of Chemical Engineering
Parc area Solid state chemistry, Preformulation
2/ Correlation between hardness of multicomponent solid forms and disintegration capability of pressed tablets
Many drugs can form numerous solid forms including polymorphs, salts, cocrystals or even amorphous solids. All these forms together with particle size has significant impact on the rate of drug dissolution, typically studied during powder dissolution. However, there are cases when the best candidates upon formulation into tables do not perform well. This is often due to poor disintegration characteristic of the tables caused by drug stickiness or powder mechanical properties. In this project, we plan to relate drug solid form hardness properties with the rate of table disintegration and consequent drug dissolution kinetics. Particularly interesting are solid solutions of drugs with polymers, for which hardness of solid solution will have similar mechanical properties that excipients used for final tablet preparation. To cover broader range of properties we would consider several excipients used during tablet formation. Apart from the measurement of the drug release rate we would also characterize the properties of formed particles using Raman spectroscopy (mapping or in-situ measurement), and in-situ particle size and morphology measurements.
Supervisor prof. Ing. Miroslav Šoóš, Ph.D. (Miroslav.Soos@vscht.cz)
University University of Chemistry and echnology, Department of Chemical Engineering
Parc area Preformulation and solid state analysis
3/ Continuous preparation of coamorphous forms of drugs and their characterization during dissolution
Coamorphous forms of drugs represent rather new approach towards enhancing the solubility of drugs. In this project, we plan to study the capability of small biomolecules, i.e. amino acids, peptides and proteins, to stabilize selected drug substances into coamorphous solid form. Commonly, the screening process is done using batch systems, such as ball mills. Building on our preliminary results, we will extend the preparation of new coamorphous form to continuous operation, using rotary extruder. Detailed DEM characterization of energy introduced into ball mill and measurement of transformation kinetics wiIl provide basis for the process scale up. Process parameters pool will cover modification of residence time, increase of temperature, drug to coformer ratio etc. Properties of coamorphous solid forms characterized with various methods (i.e. XRD, DSC, TGA, NMR) will be correlated with the dissolution rate and capability of the coformer to stabilize drug in its supersaturated solution. Since in GI tract the drug stability in supersaturated state will be affected by the action of various surface-active compounds and enzymes, we plan to study the stability of supersaturated solution in the presence of bile salts and enzymes present in GI tract. Here techniques like UV/VIS, HPLC, analyzes of precipitated particles size (if any) and Raman spectroscopy will be used to characterize drug solubility.
Supervisor prof. Ing. Miroslav Šoóš, Ph.D. (Miroslav.Soos@vscht.cz)
University University of Chemistry and echnology, Department of Chemical Engineering
Parc area Solid state chemistry, Preformulation and solid state analysis, Biopharmacy
4/ Preparation of multicomponent solid forms of cannabinoids
Cannabinoids are natural compounds, which exhibit strong activity via cannabinoid-1 and -2 receptors, and thus can find application in various drug products against inflammation (e.g. for treatment of rheumatoid arthritis) with significant commercial potential. Within this project, we plan to prepare and study the properties of multicomponent solid forms of various available cannabinoids. As coformers we will use small biomolecules but also suitable drug molecules capable to enhance the effect of cannabinoids. Obtained products will be analyzed with various analytical techniques including XRD, DSC, TGA, NMR, and dissolution rate measurement. Best candidates will be tested in animal models to compare in-vitro and in-vivo results.
Supervisor prof. Ing. Miroslav Šoóš, Ph.D. (Miroslav.Soos@vscht.cz)
University University of Chemistry and echnology, Department of Chemical Engineering
Parc area Solid state chemistry
5/ Massively paralel screening of pharmaceutical nanocomposites formed by spray drying from mixed solvents
Supervisor prof. Ing. František Štěpánek, Ph.D. (Frantisek.Stepanek@vscht.cz)
University University of Chemistry and Technology, Department of Chemical Engineering
Parc area Drug design and process
6/ Collaborative robots in pharmaceutical formulation development
Supervisor prof. Ing. František Štěpánek, Ph.D. (Frantisek.Stepanek@vscht.cz)
University University of Chemistry and Technology, Department of Chemical Engineering
Parc area Drug design and process
7/ Experimental and theoretical investigation of continuous powder blending and trituration
Supervisor prof. Ing. František Štěpánek, Ph.D. (Frantisek.Stepanek@vscht.cz)
University University of Chemistry and Technology, Department of Chemical Engineering
Parc area Drug design and process
8/ Formulation strategies for API-independent drug release
Supervisor prof. Ing. František Štěpánek, Ph.D. (Frantisek.Stepanek@vscht.cz)
University University of Chemistry and Technology, Department of Chemical Engineering
Parc area Drug design and process, Biopharmacy
9/ 3D printing of biological barriers for ex-vivo drug permeation studies
Supervisor prof. Ing. František Štěpánek, Ph.D. (Frantisek.Stepanek@vscht.cz)
University University of Chemistry and Technology, Department of Chemical Engineering
Parc area Drug design and process, Biopharmacy
10/ Surface energy heterogeneity of particulate matter
Free surface energy is one of the important parameters in industrial applications and processes of powder and fibrous materials. Differences in surface energy affect interfacial interactions such as wetting, cohesion, or adhesion. As the wide range of uses of powders is controlled by surface reactions or interactions, the characterization of surface energies can be important information for improving surface properties (eg surface modification). General theories can only be applied to smooth, molecularly flat solid surfaces or particles. However, most interfaces for particulate matter do not have an ideally smooth surface or an ideally homogenized surface, so the work will focus on determining the heterogeneity of surface properties; heterogeneity of surface energy, and its relation to other properties of these substances.
Supervisor Ing. Jan Patera, Ph.D. (Jan.Patera@vscht.cz)
University University of Chemistry and Technology, Department of Organic Technology
Parc area Preformulation and solid state analysis
11/ Monitoring and prediction of tablet disintegration behavior using texture analysis
The disintegration kinetics of tablets is a determining step for their overall dissolution behavior, as it determines the size and specific surface area of the fragments produced during their disintegration. This kinetics depends on the rate of penetration of the disintegration medium into the tablet microstructure, both into the pores and swelling components of the tablet, and the ability of the internal dissolution and swelling processes to disrupt the tablet cohesion. The aim of this work is to study the kinetics of water absorption into the tablet as a function of its composition and microstructure by means of textural analysis and microscopic measurements, to study the resistance of the tablet to erosive effects as a function of the amount of absorbed liquid as well as the size of the fragments formed as a result of these processes. The knowledge obtained should then be used to develop a fully or partially predictive model capable of predicting disintegration behavior based on the microstructure of the tablet and the physical properties of its components.
Supervisor prof. Ing. Petr Zámostný, Ph.D. (Petr.Zamostny@vscht.cz)
University University of Chemistry and Technology, Department of Organic Technology
Parc area Preformulation and solid state analysis
12/ Stability of interactive mixtures and their utilization for drug delivery
Interactive mixtures are self-organizing systems of host-guest particles that form as a result of preferential inter-surface interactions. In addition to their well-known use in powder inhalers, they may find applications in other areas of drug delivery, e.g. to increase the dissolution rate of poorly soluble drugs. The aim of this work will be to study the interparticle inter-surface interactions using surface energy measurements, atomic force microscopy, and centrifugation methods, to define the stability conditions of the interactive aggregates based on the properties measured using those methods, and to find methods of designing a stable interactive mixture for a specific drug.
Supervisor prof. Ing. Petr Zámostný, Ph.D. (Petr.Zamostny@vscht.cz)
University University of Chemistry and Technology, Department of Organic Technology
Parc area Preformulation and solid state analysis
13/ Design and optimization of unit operations for continuous manufacturing of solid dosage forms
The continuous manufacturing of solid dosage forms is a very progressive way to increase the production efficiency of products manufactured in a large number of batches. Compared to the traditional batch-oriented approach, it requires new approaches for quality control, prefers different types of unit operations and consequently, there are different preferences in the formulation of products intended for this production method. The aim of this work is to provide a new perspective on the formulation and design of technological procedures for the production of tablets and other solid dosage forms in the light of the focus on continuous manufacturing. In particular, the work will focus on continuous mixing processes, segregation of the mixture in a continuous line, roll compaction and its setup from the perspective of tablet compression.
Supervisor prof. Ing. Petr Zámostný, Ph.D. (Petr.Zamostny@vscht.cz)
University University of Chemistry and Technology, Department of Organic Technology
Parc area Drug design and process
14/ 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 comprsing 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 thos fronts corresponds 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 Chemistry and Technology, Department of Organic Technology
Parc area Biopharmacy
15/ Development of nanoparticulate formulations for targeting skin cancer
Skin tumours are identified with increasing incidence. Currently, topical treatment is substantially limited by low bioavailability of anticancer drugs. The aim of this work is development of nanoparticulate systems (e.g. liposomes, lipid and polymer nanoparticles) and monitoring their potential to target drugs into skin tumours. Nanocarriers loaded with active compounds for cancerous and precancerous stages will be prepared and characterised. Their ability to transport the drug across the skin barrier and interactions with cancer tissue will be studied in vitro. Processing of the most promising systems will be optimized for in vivo experiments in mice cancer models where the drug/nanoparticle transport and release kinetics in the tumour will be monitored. The results will contribute to fundamental understanding of relationships between the nanoformulation, its properties, and biological effects in cancer tissue.
Supervisor doc. Dr. Jarmila Zbytovská (Jarmila.Zbytovska@vscht.cz)
University University of Chemistry and Technology, Department of Organic Technology
Parc area Drug design and process, Biopharmacy
16/ Application of electrochemical oxidation in the study of stability and degradation of pharmaceutical substances
The project will follow up on the dissertation of Filip Vymyslický. During the first year, Filip Vymyslický will provide the student with his know-how in the area of electrochemical oxidation of pharmaceutical substances. The project will investigate the possibilities of the usage of electrochemical oxidation as a method of oxidative stress in the study of stability and degradation mechanisms of pharmaceutical substances. Selected compounds will be subjected to electrochemical and chemical oxidation under various conditions. Concerning electrochemical oxidation, different setups, electrochemical cells, and electrode materials, including graphitized carbon, gold, or boron-doped diamond, will be tested. After the oxidative stress, the samples will be analyzed using ultrahigh-performance liquid chromatography with UV and mass detection. The identity and quantity of degradation products formed under various conditions will be compared using statistical tools. The ultimate goal is to develop an electrochemical methodology for the study of oxidative degradation of active ingredients that would provide information complementing that achieved by classical chemical oxidation methods. Ideally, the new methodology could become a faster and less costly alternative and replace the chemical oxidation in the future.
Supervisor RNDr. Tomáš Křížek, Ph.D. (Tomas.Krizek@natur.cuni.cz)
University Charles University, Faculty of Science, Department of Analytical Chemistry
Parc area Preformulation and solid state analysis
17/ Testing of lymphatic drug absorption
There is a potential use of lymphatic system as a pathway for drug delivery due to its unique anatomy and physiology. Lymphatic transport of drugs upon oral administration offers certain advantages, such as first-pass liver effect elimination, targeting drugs to specific lymphatic tissues and increasing their overall systemic bioavailability. The aim of this Ph.D. programme is to study the lymphatic absorption of selected drugs using anesthetized rat model with cannulated lymph duct and to develop a novel pig model.
Supervisor PharmDr. Martin Šíma, Ph.D. (martin.sima@lf1.cuni.cz)
University Charles University, First Faculty of Medicine, Institute of Pharmacology
Parc area Preclinical in-vivo testing
18/ Preclinical in-vivo testing of pharmacokinetics
This research area focuses on development and subsequent utilization of appropriate pre-clinical in vivo models to describe drug pharmacokinetics in vivo. We focus on physiological factors affecting bioavailability and drug fate in the organism as well as determination of pharmacokinetic characteristics of various formulation modifications or alternative ways of drug administration. Broad aim of this research area is to predict formulation-specific pharmacokinetic properties in men based on pre-clinical data.
Supervisor PharmDr. Martin Šíma, Ph.D. (martin.sima@lf1.cuni.cz)
University Charles University, First Faculty of Medicine, Institute of Pharmacology
Parc area Preclinical in-vivo testing
19/ Development of Lymphatic Transport-Targeting Prodrugs
Absorption of the drugs through lymphatic system has received increasing attention in recent years. Especially in therapeutic areas such as autoimmune disorders, metabolic syndrome, cancer, HIV infection or vaccination, absorption through lymph play an important role. Lymph targeted drug exposure would suppress the first-pass metabolism in liver and increase the pharmacodynamic effect. Re-routing the pathway of drug absorption from the portal blood to the intestinal lymph might be done by several approaches as lipid-based formulations (polymeric or liposomal nanomaterials, lipid nanoparticles or microspheres, permeation enhancers) or lipid prodrug synthesis. The later one, is preferred strategy especially for the compounds with low lipophilicity (log P<5). Development of new self-immolative lipophilic prodrugs, being absorbed through intestinal lymph vessels and subsequently releasing drug substance into systemic circulation represent innovative approach which could enhance the poor bioavailability of many drug candidates, allowing dose reduction, suppressing the food effect and in the same time mitigate the toxic adverse events to patients and minimize the environmental impact.
Supervisor Ing. Petra Ménová, Ph.D. (Petra.Menova@vscht.cz)
University University of Chemistry and Technology, Department of Organic Chemistry
Parc area Drug design and process
March 4. 2022