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 2023!
____________________________________
PhD topics overview
01/ Continuous preparation of coamorphous forms of drugs and their characterization during dissolution
02/ Development and optimization of continuous wet granulation process
03/ Design and optimization of unit operations for continuous manufacturing of solid dosage forms
04/ Modeling of drug release from the solid dispersions by diffusion erosion models
05/ Monitoring and prediction of tablet disintegration behavior using texture analysis
06/ Stability of interactive mixtures and their use for drug delivery
07/ The use of surface energy as a tool for the formulation applications
08/ Development of liquisolid systems with controlled drug release
09/ Improving drug solubility via liquisolid systems preparation
10/ Biopharmaceutical testing of mesoporous silica-based systems
11/ Development of nanoparticulate formulations targeting skin cancer
12/ Advanced formulations for skin barrier recovery
13/ Alternative routes of administration of small synthetic peptides and oligonucleotides
14/ Improving the pharmacokinetic and pharmacodynamic properties of drugs using lymphatic absorption
15/ Advanced engineering approaches to continuous processing of pharmaceutical nanosuspensions
16/ Investigation of colligative properties during membrane permeation of pharmaceutical substances
17/ Reduction of materials consumption in pharmaceutical manufacturing processes
18/ Advanced formulation processes combining fluidised bed coating and automatic particle blending
19/ Development of advanced analytical and formulation approaches for increased stability of pharmaceutical products
____________________________________
1/ 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 small-scale batch systems, such as ball mills. Building on our preliminary results, we will extend the preparation of new coamorphous form towards continuous operation using rotary extruder. Detailed DEM characterization of energy introduced into ball mill and measurement of transformation kinetics will provide basis for the process scale up. Process parameters pool will cover residence time, increase of temperature, drug to coformer ratio, mixing intensity and applied shear rate. 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 Technology, Department of Chemical Engineering
Parc area: Solid state chemistry, Preformulation
2/ Development and optimization of continuous wet granulation process
Wet granulation process is commonly used to increase of drug particle size, improve of drug particle flowability or its physicochemical properties. Commonly, the wet granulation process is done in a batch mode using high shear granulators. However, during the process scale up there is often difference in the final granule properties including size, composition, homogeneity, porosity etc. All these parameters have impact on the rate of drug product disintegration and drug dissolution. Therefore, the main goal of this work is to develop and optimize process of wet granulation using continuous operation mode via extrusion process. Process parameters will cover ratio of drug particle to binder, binder type, size and surface properties of drug particles, mixing intensity, applied shear rate and residence time in the extruder. Obtained granules will be characterized by a combination of various methods including API crystal form stability (XRD), size characterization (optical and electron microscopy, light scattering), porosity measurement (BET, Hg porosimetry, tomography), composition (Raman mapping, FTIR, NIR spectroscopy), powder rheology and granule disintegration kinetic. Collected results will be compared with those measured for granules obtained from batch process, targeting development of criteria for process transfer from small-scale batch process to continuous operation.
Supervisor: prof. Ing. Miroslav Šoóš, Ph.D. (Miroslav.Soos@vscht.cz)/ 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
3/ 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
4/ 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, Drug design and process
5/ 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
6/ Stability of interactive mixtures and their use 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
7/ The use of surface energy as a tool for the formulation applications
Pharmaceutical products are sophisticated mixtures of numerous compounds that can be liquids or solids. However, there is still the problem how to select them efficiently without costly and time-consuming tests that are associated with the complexity of the drug development. Surface energy could be used as powerful prediction tool to perform such selections. The aim of this work is to provide a new perspective on the prediction of component compatibility (API and excipient) for formulation design for the production of solid dosage forms based on the surface properties of their components.
Supervisor: Ing. Tereza Školáková, Ph.D. Tereza.Skolakova@vscht.cz)
University: University of Chemistry and Technology, Department of Organic Technology
Parc area: Preformulation, Drug design and process
8/ Development of liquisolid systems with controlled drug release
Liquisolid systems represent novel formulations intended to improve the bioavailability of poorly soluble drugs. Liquisolid systems are commonly used to improve the dissolution rate of poorly soluble drugs. However, controlled release can be achieved for these systems if they are combined with retarding agents. Therefore, the project will focus on developing and evaluating novel liquisolid systems with controlled release of poorly soluble drugs. The main aims of the project will include designing a drug delivery system capable of releasing the drug at the specific site of the gastrointestinal tract (e.g., colon) in a controlled manner.
Supervisor: doc. PharmDr. Barbora Vraníková, Ph.D. (vranikovab@faf.cuni.cz)
University: Charles University, Faculty of Pharmacy, Department of Pharmaceutical Technology
Parc area: Drug design and process
9/ Improving drug solubility via liquisolid systems preparation
Liquisolid systems (LSS) represent novel formulations intended to improve the bioavailability of poorly soluble drugs. Their preparation is based on the sorption of the drug in the liquid state into the porous structure of the carrier material, which is subsequently coated by very fine particles of coating material. The project will focus on the development of liquisolid systems with the aim to reduce the amount of excipients needed for drug conversion and facilitating their production.
Supervisor: doc. PharmDr. Barbora Vraníková, Ph.D. (vranikovab@faf.cuni.cz)
University: Charles University, Faculty of Pharmacy, Department of Pharmaceutical Technology
Parc area: Drug design and process
10/ Biopharmaceutical testing of mesoporous silica-based systems
It has been proven that mesoporous silica materials have the potential to increase the solubility of poorly water-soluble drugs by nanoconfinement of drug amorphous form in pores and hence keeping them from recrystallization. However, interactions between the drug molecules and the silica surface can lead to incomplete drug release, which has been reported in several studies. The strength of such interaction may be affected by the silica surface chemistry, which varies as a function of the pH, drug chemistry and ionization states. Accordingly, the main objective of this project is to identify the mechanisms underlying the incomplete drug release from non-ordered mesoporous silica-based systems. The non-sink dissolution test, the Brunauer-Emmett-Teller isotherm equation adapted for solution phase adsorption and thermodynamic analysis will be performed at varying conditions (pH and ionic strength of media) to elucidate the character of interactions and their role in incomplete drug release. As a result, the displacer molecules (bile salts, amino acids, lipids) will be employed to improve drug release extent by competing with the drug molecules during the readsorption process. The project outcomes are expected to deepen knowledge and understanding of interactions between the drugs and mesoporous silica carriers in oral drug delivery systems containing poorly water-soluble drugs.
Supervisor: doc. PharmDr. Barbora Vraníková, Ph.D. (vranikovab@faf.cuni.cz)
University: Charles University, Faculty of Pharmacy, Department of Pharmaceutical Technology
Parc area: Drug design and process, Preformulation
11/ Development of nanoparticulate formulations 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 and ex vivo. 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
12/ Advanced formulations for skin barrier recovery
Ceramides are essential components of the skin barrier. Many skin diseases, e.g. atopic dermatitis or psoriasis, are connected with their pathological biosynthesis and decreased levels in the stratum corneum, the outermost skin layer. Simple topical application of ceramides shows, however, a basic shortcoming – minimum skin bioavailability. Therefore, development of advanced nanoparticulate formulations targeting ceramides right into the skin barrier seems to be a promising therapeutical procedure.
The aim will be development of advanced nanoparticulate formulations with ceramides. Optimum process procedures, composition, and scale-up possibilities will be screened. Efficiency of the formulations will be studied in vitro in cell cultures and ex vivo in isolated skin. To characterize the mode of action of the formulations, biophysical techniques will be applied on order to monitor interactions with the skin barrier. The best formulations will be tested also in vivo on animal models.
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
13/ Alternative routes of administration of small synthetic peptides and oligonucleotides
Many small peptides are known to us as intrinsic substances whose substitution is necessary in many diseases. At the same time, they can be prepared synthetically, which classifies them as structurally defined, i.e. not biological, drugs. Therapeutic oligonucleotides (including siRNA) have high therapeutic potential in a number of diseases. They undergo rapid clearance at the systemic level, particularly via the kidney.
A common problematic feature of both these groups of drugs is their very low oral bioavailability, which precludes an oral route of administration. An interesting alternative, non-invasive yet minimally exploited route of administration may be intranasal or inhaled administration.
The aim will be to study the possibility of alternative routes of administration of synthetic peptides and oligonucleotides (e.g. semaglutide, hCG, oxitocin, teriaparatide, siRNA, etc.) in relation to their biological effects in vivo. Prospective peptides such as the recently discovered orexins (orexin A, orexin B), which are physiologically synthesized in hypothalamic neurons and whose absolute deficiency conditions type I narcolepsy, will also be studied.
Supervisor: prof. MUDr. Ondřej Slanař, Ph.D. (ondrej.slanar@lf1.cuni.cz)
University: Charles University, First Faculty of Medicine, Institute of Pharmacology
Parc area: Preclinical in-vivo testing
14/ Improving the pharmacokinetic and pharmacodynamic properties of drugs using lymphatic absorption
Lymphatic absorption of drugs is an important, although still poorly understood, route of absorption after oral administration for highly lipophilic substances. Absorption of drugs from the intestine into the mesenteric lymphatic system can provide a number of therapeutic benefits. Here, substances commonly reach concentrations up to a thousand times higher than in plasma. This can be exploited when targeting lymphocytes and other immune system cells that are naturally concentrated in the lymph. Another advantage is the avoidance of the liver, which leads to increased bioavailability of substances that are otherwise rapidly metabolized.
Lymphatic absorption of drugs can be increased in several ways. For lipophilic substances (log P>5), it is necessary to create a high quality lipid drug formulation that ensures good dispersion of the substance in the gastrointestinal tract, and the lipids contained subsequently become the building blocks of lipoproteins that are secreted into the lymph and transport the drug. In the case of less lipophilic substances (log P<5), targeting to the lymph is more complex but also possible by synthesis of a highly lipophilic prodrug that is transported to the lymph and subsequently released.
The aim of the study will be to collaborate on the development of advanced lipid drug forms for enhancing lymphatic absorption and their in vivo testing in animal models.
Supervisor: MUDr. Pavel Ryšánek, Ph.D. (pavel.rysanek@lf1.cuni.cz)
University: Charles University, First Faculty of Medicine, Institute of Pharmacology
Parc area: Preclinical in-vivo testing
15/ Advanced engineering approaches to continuous processing of pharmaceutical nanosuspensions
Nanosuspensions of active pharmaceutical ingredient (API) represent an emerging field in pharmaceutical formulation processes as they enable precise control over dissolution properties while maintaining the API in its thermodynamically most stable crystalline form. Nanosuspensions are typically prepared by either bottom-up (antisolvent precipitation) or top-down (wet stirred media milling) processes, each of which has its pluses and minuses. Due to flow assurance, mixing rate and solubility limitations, antisolvent precipitation cannot achieve very high concentrations of the nanosuspensions, thus requiring large volumes of solvent to be evaporated in the subsequent formulation steps such as spray coating or granulation. Ball milling often exposes the API particles to prolonged mechanical and thermal stress, which can lead to degradation. The project will aim to investigate the combination of bottom-up and top-down approaches in such a way that both API mass fraction in the suspension, and API:stabiliser ratio can be maximised. Antisolvent precipitation will ensure controlled nucleation while ball milling will ensure efficient milling and prevent the formation of large API clusters. The project will also involve subsequent processing of nanosuspensions into solid dosage forms (coated pellets or granules) that ensure good redispersion and dissolution properties.
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
16/ Investigation of colligative properties during membrane permeation of pharmaceutical substances
Drug permeation across biological barriers is a crucial property with a direct influence on pharmacokinetics and bioavailability. So far, permeability has been considered only a property of the drug molecule itself, as reflected by the well-established Biopharmaceutics Classification System (BCS). However, it has been recently observed that during simultaneous permeation of two or more substances across a lipidic bi-layer, significant interactions can exist, and the same substance can permeate by more than an order of magnitude faster or slower depending on the presence of other permeants. This project aims to understand this fascinating behaviour by a combination of systematic experiments and molecular simulations. These "colligative" permeation properties will be investigated, the most strongly interacting small-molecule drugs will be identified and hypotheses regarding the origin of their interaction will be tested. Experimental and computational tools for the prediction of drug interactions during permeation will be developed, which will enable a rational approach to future combination therapy.
Supervisor: prof. Ing. František Štěpánek, Ph.D. (Frantisek.Stepanek@vscht.cz)
University: University of Chemistry and Technology, Department of Chemical Engineering
Parc area: Biopharm
17/ Reduction of materials consumption in pharmaceutical manufacturing processes
Many pharmaceutical tablets contain a large volume of excipients without any obvious technological or clinical benefit. Often the excipient volume is simply a consequence of a lack of (or no need for) formulation optimisation during the development of the original drug product. However, for large-volume medicines after original patent expiry, there are numerous reasons for trying to reduce the volume of excipients in tablets. These include economic (cost of materials, production time), environmental (size of packaging, carbon footprint of production and distribution), quality (excipients are often the source of reactive impurities that result in degradation) and clinical (large tablets are more difficult to swallow). Therefore, the aim of this project is to identify pharmaceutical products with the most significant potential for excipient reduction, to reformulate such products while maintaining bioequivalence, and to demonstrate manufacturing and/or patient benefits. General methodology for excipient reduction based on the material properties (e.g. flowability, adhesion) will be developed. The project will involve both fundamental scientific understanding real-world case 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
18/ Advanced formulation processes combining fluidised bed coating and automatic particle blending
Fluid-bed coating and granulation are robust and well-established processes in the pharmaceutical industry. Yet, their potential for product performance optimisation (e.g customised dissolution profiles) is far from being fully exploited. For example, pellet coating and layering can provide a very effective way of controlling dissolution profiles. Fluid-bed coating can also be an alternative to the formation of amorphous solid dispersions by spray drying. Finally, the formation of custom particle mixtures from "fast" and "slowly" dissolving pellets can represent a highly flexible way of creating products with arbitrarily customisable dissolution profiles, which can be beneficial for example in the case of personalised medicine or when preparing prototypes for "fail-proof" bioequivalence studies. The aim of this project will be to investigate the combination of fluid-bed and automatic mixing processes, to develop a general methodology for product design with "on demand" dissolution profile, and to demonstrate the feasibility of such approaches on several case 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
19/ Development of advanced analytical and formulation approaches for increased stability of pharmaceutical products
Many pharmaceutical excipients contain trace amounts of reactive impurities that contribute to the degradation of the active pharmaceutical ingredient (API) during manufacturing and storage. With ever more stringent regulatory requirements, it is necessary to address even low levels of impurities that were previously tolerated and can often be found in currently marketed products. The aim of the project it two-fold: (1) to develop advanced analytical methods for the detection of such impurities and the prediction of their formation kinetics under various conditions such as temperature and humidity, and (2) to propose and test innovative formulation approaches that can reduce or suppress the underlying cause of API reactive degradation. The project will include both fundamental research and real-world case 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
April 6. 2023