Frantisek Stepanek

Frantisek Stepanek
University of Chemistry and Technology, Prague | VSCHT · Faculty of Chemical Engineering

About

262
Publications
25,245
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4,598
Citations
Citations since 2017
59 Research Items
2347 Citations
20172018201920202021202220230100200300400
20172018201920202021202220230100200300400
20172018201920202021202220230100200300400
20172018201920202021202220230100200300400

Publications

Publications (262)
Article
Nilotinib is a selective tyrosine-kinase inhibitor approved for the treatment of chronic myeloid leukemia. It is poorly soluble in aqueous media and has a low oral bioavailability. Nilotinib encapsulation into yeast glucan particles (GPs) was investigated in this work as a means of increasing bioavailability. The amorphization of nilotinib in GPs r...
Article
In article 2200115, Denisa Lizoňová and co‐workers describe a methodology based on fluorescence microscopy, where curcumin nanocrystals can be distinguished from cell‐dissolved curcumin due to differences in fluorescence emission spectra. Thanks to this, the curcumin in the cells is visualized as blue (thus blue macrophage) and nanocrystals as red....
Article
Encapsulation of active compounds into liquid marbles (LMs) represents an emerging technology with potential applications in several fields including food, cosmetics and pharmaceutics. However, existing methods for the preparation of LMs are either based on manual one-by-one fabrication or on batch processes such as high-shear granulation, which la...
Article
Three-dimensional cell culture systems are increasingly used for biological and anticancer drug screening as they mimic the structure and microenvironment of tumors more closely than conventional two-dimensional cell models. In this study, the growth kinetics of colon adenocarcinoma-derived spheroids (HT-29 cell line) cultivated in liquid marble mi...
Article
Drug nanocrystals represent an effective way of delivering poorly water‐soluble substances to target tissues and cells. Due to large specific surface area, nanocrystals promote dissolution, and therefore the drug usually co‐exists in both crystalline and dissolved forms. Commonly used analytical methods do not make it possible to easily distinguish...
Article
Full-text available
Purpose Fluid-bed coating processes make it possible to manufacture pharmaceutical products with tuneable properties. The choice of polymer type and coating thickness provides control over the drug release characteristics, and multi-layer pellet coatings can combine several active ingredients or achieve tailored drug release profiles. However, the...
Article
Pharmaceutical nanocrystals represent a promising new formulation that combines the benefits of bulk crystalline materials and colloidal nanoparticles. To be applied in vivo, nanocrystals must meet several criteria, namely colloidal stability in physiological media, non-toxicity to healthy cells, avoidance of macrophage clearance, and bioactivity i...
Article
Drug depot systems have traditionally relied on the spontaneous dissolution and diffusion of drugs or prodrugs from a reservoir with constant exposure to the surrounding physiological fluids. While this is appropriate for clinical scenarios that require constant plasma concentration of the drug over time, there are also situations where multiple bu...
Article
Dissolution testing is widely used to measure the rate of drug release and predict its in-vivo behavior. The release rate can be controlled by adjusting the particle size distribution (PSD). However, experimental investigation of various particle sizes requires many time-consuming experiments. To reduce the need for them, we propose an optimization...
Article
The aim of this work was to develop a single-step process to produce hydroxyapatite/polycaprolactone (HAp/PCL) composite filaments for 3D printing of bone scaffolds by fused deposition modelling (FDM). The HAp/PCL composite filaments were produced by hot-melt extrusion, with direct in situ blending. For practical purposes, the effect of PCL particl...
Article
Background and purpose: Lymphatic transport of drugs after oral administration is an important mechanism for absorption of highly lipophilic compounds. Direct measurement in lymph duct cannulated animals is the gold standard method, but non-invasive cycloheximide chylomicron flow blocking method has gained popularity recently. However, concerns ab...
Article
The sorption of poorly aqueous soluble active pharmaceutical ingredients (API) to mesoporous silica carriers is an increasingly common formulation strategy for dissolution rate enhancement for this challenging group of substances. However, the success of this approach for a particular API depends on an array of factors including the properties of t...
Article
Silica particles find applications in drug delivery and bio-sensing, where their large specific surface area can accumulate or release biologically active substances. Such applications would benefit from the ability to control diffusion access to the surfaces of a larger number of silica particles simultaneously. In the present work, we show that a...
Article
A multi-material 3D printing offers nearly endless possibilities for the spatial arrangement of individual materials within the object being printed. In the case of pharmaceutical tablets, the spatial arrangement of individual material domains containing the active pharmaceutical ingredients (APIs) and excipients uniquely defines the release profil...
Article
Yeast glucan particles are porous polysaccharide cell walls extracted from Saccharomyces cerevisiae. Being mildly immunogenic, they are efficiently phagocytosed and have therefore been proposed as possible vehicles for drug delivery. Using curcumin as a model poorly water-soluble drug, a systematic comparison of three different physical loading met...
Article
Full-text available
Garlic is a well-known example of natural self-defence system consisting of an inactive substrate (alliin) and enzyme (alliinase) which, when combined, produce highly antimicrobial allicin. Increase of alliinase stability and its activity are of paramount importance in various applications relying on its use for in-situ synthesis of allicin or its...
Article
Lipid bilayers are the basic structural components of all living systems, forming the membranes of cells, sub-cellular organelles, and extracellular vesicles. A class of man-made lipidic vesicles called multilobed magnetic liposomes (MMLs) is reported in this work; these MMLs possess a previously unattained combination of features owing to their un...
Article
Wurster fluid bed coating is an effective way of manufacturing pharmaceutical pellets requiring specific characteristics such as high drug loading or enteric protection. The optimization of coating process can be demanding because it necessitates many time-consuming experiments. To reduce the need for experiments and prevent undesired agglomeration...
Article
Full-text available
Liposomal formulations can be advantageous in a number of scenarios such as targeted delivery to reduce the systemic toxicity of highly potent Active Pharmaceutical Ingredients (APIs), to increase drug bioavailability by prolonging systemic circulation, to protect labile APIs from degradation in the gastrointestinal tract, or to improve skin permea...
Article
Yeast glucan particles (GPs) are promising agents for the delivery of biologically active compounds as drugs. GPs possess their own biological activities and can act synergistically with their cargo. This study aimed to determine how incorporating artemisinin, ellagic acid, (-)-epigallocatechin gallate, morusin, or trans-resveratrol into GPs affect...
Article
The goal of this work was to assess the usability of yeast glucan particles (GPs) as carriers for curcumin and determine the beneficial effect of a pharmacological composite of curcumin in GPs on dextran sulfate sodium induced colitis in rats. The assessment of the anti-inflammatory effect of particular substances was evaluated on the basis of the...
Article
Tablets are the most common pharmaceutical dosage form. Being compressed from smaller particles or granules, the disintegration rate of tablets in the gastro-intestinal tract is a key property that strongly influences the rate of drug release. While established methods for in vitro tablet disintegration measurement provide information about the fin...
Article
Abiraterone acetate has limited bioavailability in the fasted state and exhibits a strong positive food effect. We present a novel formulation concept based on the so-called oil marbles (OMs) and show by in vitro and in vivo experiments that the food effect can be suppressed. OMs are spherical particles with a core-shell structure, formed by coatin...
Article
Microfluidics allows to accurately control the synthesis of microparticles for specific applications, where size and morphology play an important role. In this work, we introduce microfluidic chip design with dedicated extraction and gelation sections allowing to prepare hydrogel particles in size range of a red blood cell. The influence of the ext...
Article
Efficient tablet disintegration is a pre-requisite for fast and complete drug dissolution from immediate release formulations. While the overall tablet disintegration time is a routinely measured quality attribute of pharmaceutical products, little attention is usually paid to the analysis of disintegration fragments and the cascade of elementary s...
Preprint
Full-text available
Liposomal formulations can be advantageous in a number of scenarios such as targeted delivery to reduce the systemic toxicity of highly potent Active Pharmaceutical Ingredients (APIs), to increase drug bioavailability by prolonging systemic circulation, to protect labile APIs from degradation in the gastrointestinal tract, or to improve skin permea...
Article
Abiraterone acetate is a potent drug used for the treatment of metastatic castration resistant prostate cancer. However, currently marketed product containing crystalline abiraterone acetate exhibits strong positive food effect which results in strict dosing regimen. In the present work, a rational approach towards design of novel abiraterone aceta...
Article
Natural compounds offer a wide spectrum of potential active substances, but often they have a poor bioavailability. To increase the bioavailability and bioactivity of the natural anti-inflammatory molecules curcumin and diplacone, we used glucan particles (GPs), hollow shells from Saccharomyces cerevisiae composed mainly of β-1,3-d-glucan. Their in...
Article
Amorphisation using mesoporous inorganic carriers represents an emerging formulation strategy for the dissolution rate enhancement of poorly water-soluble Active Pharmaceutical Ingredients (APIs). This approach employs API loading to a porous carrier, which stabilises the amorphous form and prevents recrystallisation due to spatial confinement in t...
Article
In this work, novel amorphous solid dispersions based on yeast glucan particles were produced. Yeast glucan particles are hollow and porous, and they are mainly composed of amorphous polysaccharides. We hypothesized that these particles are suitable candidates for the amorphization of drugs with low water solubility. Model drugs ibuprofen and curcu...
Article
Glucan particles derived from yeast have been recently proposed as potential drug delivery carriers. Here, we demonstrate the potential of glucan particles for protein delivery in vivo, using the insect Drosophila melanogaster as a model organism. By employing genetic tools, we demonstrate the capacity of yeast glucan particles to spread efficientl...
Article
Over the past decade, continuous wet granulation has been emerging as a promising technology in drug product development. In this paper, the continuous high-shear mixer granulator, Lӧdige CoriMix® CM5, was investigated using a low-dose formulation with acetaminophen as the model drug. Design of experiments was deployed in conjunction with multivari...
Article
Particle size reduction to sub-micrometer dimensions in stirred media mills is an increasingly common formulation strategy used for improving the bioavailability of poorly aqueous soluble active pharmaceutical ingredients (APIs). Due to their hydrophobic character, the API particles need to be stabilised by a surfactant in order to form a stable na...
Article
Glucan particles (GPs) from Saccharomyces cerevisiae are hollow shells that are composed mainly of β-1,3-d-glucan, which has demonstrated immunomodulatory and anti-inflammatory potential both in vitro and in vivo. Curcumin is a natural hydrophobic phenolic compound, which possesses a significant anti-inflammatory effect and is used as supportive th...
Article
The lack of specificity of traditional cytostatics and increasing resistance of cancer cells represent important challenges in cancer therapy. One of the characteristics of cancer cells is their intrinsic oxidative stress caused by higher metabolic activity, mitochondrial malfunction and oncogene stimulation. This feature can be exploited in the pu...
Article
Discrete Element Method (DEM) simulations of elongated (i.e. needle-shaped) particles breakage in a shear field confined between two parallel plates, in analogy with processes occurring in a powder shear cell tester, were carried out. Effects of particle strength, shear rate and the compressive stress were investigated. The breakage patterns occurr...
Article
Full-text available
Many new therapeutic candidates and active pharmaceutical ingredients (APIs) are poorly soluble in an aqueous environment, resulting in their reduced bioavailability. A promising way of enhancing the release of an API and, thus, its bioavailability seems to be the use of liquid oil marbles (LOMs). An LOM system behaves as a solid form but consists...
Article
The manufacture of personalised medicines where specific combinations of active pharmaceutical ingredients (APIs) and their dose within a tablet would be adjusted to the needs of individual patients, would require new manufacturing approaches compared to the established practice. In the case of low-dose formulations, the required precision of API c...
Article
Increasing the dissolution rate of poorly water-soluble active pharmaceutical ingredients (APIs) is a key strategy used for improving their oral bioavailability. One of the formulation approaches is API loading to mesoporous carrier particles, which can increase the dissolution rate through the combination of improved powder wettability and dispers...
Article
Full-text available
The problem of designing tablet geometry and its internal structure that results into a specified release profile of the drug during dissolution was considered. A solution method based on parametric programming, inspired by CAD (computer-aided design) approaches currently used in other fields of engineering, was proposed and demonstrated. The solut...
Article
Single drop impact of liquid on a static powder bed was studied to investigate the granule formation mechanism, droplet penetration time, as well as the characterization of granules (morphology, surface structure and internal structure). Water was used as the liquid and two pharmaceutical powders, microcrystalline cellulose (MCC) and acetaminophen...
Article
Silica particles with a unique multi-level pore structure have been prepared in order to enable efficient melt-in amorphisation of pharmaceutical substances. The dissolution rate of drugs with a low aqueous solubility can be enhanced by their conversion from a crystalline to an amorphous form. In order to avoid spontaneous re-crystallisation over t...
Article
Full-text available
The systemic application of highly potent drugs such as cytostatics poses the risks of side effects, which could be reduced by using a carrier system able to specifically deliver the encapsulated drug to the target tissue. Essential components of a nanoparticle-based drug delivery system include the drug carrier itself, a targeting moiety, and a su...
Article
A colloidal system able to act as a miniature reactor for on-demand release of reactive payloads has been demonstrated. The system is based on sub-micrometers aggregates consisting of anionic liposomes that act as storage reservoirs for the reactants, superparamagnetic iron oxide nanoparticles (SPION) that enable magnetic positioning in space and c...
Article
This study investigates the extent of drug (active) migration in granules made via high shear wet granulation subject to factors such as the viscosity of the binder solution, particle size of the excipient and granule porosity. Due to the complexity of a qualitative comparison between granules having different sizes, shape and porosities, a quantif...
Article
We report on synthesis, preparation and characterization of newly prepared hyperbranched polyimide (HBPI) based on 4,4´-(hexafluoroisopropylidene)diphthalic anhydride (6FDA) and 4,4′,´´-triaminotriphenylmethane (TTM). HBPI material was synthesized via the amine-terminated hyperbranched polyamic acid (HBPAA) precursor and the absence of correspondin...
Article
Using a pharmaceutical formulation, granule batches were produced at a range of granulator volumes from 0.5 L to 400 L and process conditions, characterised by the Froude number in the range from Fr = 0.26 to Fr = 1.63. The mean values and the standard deviations of granule porosity, granule stiffness and granule dissolution rate evaluated from eac...
Article
Protocells are objects that mimic one or several functions of biological cells and may be embodied as solid particles, lipid vesicles, or droplets. Our work is based on using decanol droplets in an aqueous solution of sodium decanoate in the presence of salt. A decanol droplet under such conditions bears many qualitative similarities with living ce...
Article
Liquid droplets are very simple objects present in our everyday life. They are extremely important for many natural phenomena as well as for a broad variety of industrial processes. The conventional research areas in which the droplets are studied include physical chemistry, fluid mechanics, chemical engineering, materials science, and micro- and n...
Article
In this study, the origins of granule content non-uniformity in the high-shear wet granulation of a model two-component pharmaceutical blend were investigated. Using acetaminophen as the active pharmaceutical ingredient (API) and microcrystalline cellulose as the excipient, the distribution of the API across the granule size classes was measured fo...
Article
Full-text available
PurposeImaging methods were used as tools to provide an understanding of phenomena that occur during dissolution experiments, and ultimately to select the best ratio of two polymers in a matrix in terms of enhancement of the dissolution rate and prevention of crystallization during dissolution. Methods Magnetic resonance imaging, ATR-FTIR spectrosc...
Article
Full-text available
A novel continuous fluidic method based on extractive crystallization for producing monodisperse spherical crystal aggregates with potential use in pharmaceutical engineering is presented. A model system of aqueous solution containing KCl as the precursor dispersed phase and 1-hexanol as the continuous extraction phase was investigated experimental...
Article
The formation of drug carriers able to incorporate multiple molecular payloads in separate compartments was investigated, using the hetero-aggregation of oppositely charged hydrogel microparticles as the building blocks. The primary particles – negatively charged alginate and positively charged chitosan microgels with a mean diameter of 6–7 μm – we...
Article
The combination of nanoparticles with the polymerase chain reaction (PCR) can have benefits such as easier sample handling or higher sensitivity, but also drawbacks such as loss of colloidal stability or inhibition of the PCR. The present work systematically investigates the interaction of magnetic iron oxide nanoparticles (MIONs) with the PCR in t...
Article
The ability to simulate the 3D structure of a human body is essential to increase the efficiency of drug development. In vivo conditions are significantly different in comparison to in vitro conditions. A standardly used cell monolayer on tissue culture plastic (2D cell culture) is not sufficient to simulate the transfer phenomena occurring in livi...
Article
Injectable depot formulations are aimed at providing long-term sustained release of a drug into systemic circulation, thus reducing plasma level fluctuations and improving patient compliance. The particle size distribution of the formulation in the form of suspension is a key parameter that controls the release rate. In this work, the process of we...
Article
Active pharmaceutical ingredients (APIs) with strongly pH-dependent aqueous solubility can face the problem of precipitating from solution when the pH changes from acidic in the stomach to neutral in the intestine. The present work investigates the effect of two polymeric excipients – polyvinylpyrrolidone (PVP) and Soluplus – on the ability to eith...
Article
The aim of this study was to follow the skin penetration of a model lipophilic compound (Nile red) delivered by nanoparticulate carriers, the so-called lipid nanocapsules. The nanocapsules consisting of an oil core stabilized by amixture of surfactants were prepared by the phase inversion temperature method. Varying the particle composition (the oi...
Article
Full-text available
The objective of this work was to study the granulation behavior of three different types of zirconium hydroxide, each varying in particle size and density. Different concentrations of yttrium (III) nitrate hexahydrate (Y(NO3)(3)center dot 6H(2)O) solutions were used as a doping agent and also acted as binder. Experiments were performed using a hig...
Article
Yeast glucan particles (YGPs) are biopolymeric hollow shells obtained from Saccharomyces cerevisiae (baker's yeast) cells by removing internal organelles and cell wall components apart from β-glucans. Due to their biocompatibility and size in the micrometer range, YGPs could be used as naturally sourced microcapsules in areas such as functional foo...
Article
In pharmaceutical industry, the use of lubricants is mostly based on historical experiences or trial and error methods even these days. It may be demanding in terms of the material consumption and may result in sub-optimal drug composition. Powder rheology enables more accurate monitoring of the flow properties and because the measurements need onl...
Article
Nanocrystals have received considerable attention in dermal application due to their ability to enhance delivery to the skin and overcome bioavailability issues caused by poor water and oil drug solubility. The objective of this study was to investigate the effect of nanocrystals on the mechanism of penetration behavior of curcumin as a model drug....
Article
Pattern formation in far from equilibrium systems is observed in several disciplines including biology, geophysics, and reaction-diffusion chemistry, comprising both living and nonliving systems. We aim to study such non-equilibrium dynamics on a lab-scale with materials of simple composition. We present a novel system based on a 1-decanol droplet...
Article
The effect of process scale-up from 4 to 400-L high-shear granulator on the release kinetics of the active ingredient from pharmaceutical granules has been investigated. The dissolution and disintegration rates of the granules were measured simultaneously by the combination of UV/vis spectroscopy and static light scattering. The granule batches wer...
Article
Composite porous silica-iron oxide nanoparticles with the ability to store chemical payloads and release them upon triggering a radiofrequency field were prepared. The particle structure consisted of a hollow porous silica core, covered with a layer of iron oxide nanoparticles bound to the silica surface by electrostatic forces. The particle size d...
Article
The formation of multi-compartmental colloidal particles by controlled aggregation of 100 nm cationic liposomes was investigated. The aggregation was performed under quiescent (perikinetic) conditions and was controlled by the ionic strength of the solution. The time required for obtaining 500 nm particles by liposome aggregation ranged from severa...
Article
Understanding the relationship between the applied stress and the behaviour of packings of breakable granular particles is required in many chemical engineering applications. A pharmaceutical tablet is an example where a composite packing (a packing containing a mixture of several kinds of particles) is compacted in the process of tablet formation....
Article
In this study, we investigated the release mechanism of the poorly water soluble drug aprepitant from different amorphous solid dispersions using confocal Raman microscopy (CRM). Solid dispersions were fabricated based on either Soluplus®, as an amphiphilic copolymer and solubilizer, or on polyvinylpyrrolidone, as a hydrophilic polymer, in order to...
Article
The objective of this work was to study the granulation behavior of three different types of zirconium hydroxide, each varying in particle size and density. Different concentrations of Yttrium (III) Nitrate Hexahydrate (Y(NO3)3·6H2O) solutions were used as a doping agent and also acted as binder. Experiments were performed using a high shear wet gr...
Article
The rate of drug release from polymer matrix-based sustained release formulations is often controlled by the thickness of a gel layer that forms upon contact with dissolution medium. The effect of formulation parameters on the kinetics of elementary rate processes that contribute to gel layer formation, such as water ingress, polymer swelling and e...
Article
The fabrication of alginate hydrogel microparticles with embedded liposomes and magnetic nanoparticles for radiofrequency controlled release of encapsulated chemical cargo was considered. An extractive gelation process was implemented in a microfluidic device, which enabled the production of uniform composite microparticles of dimensions comparable...
Article
Polymorphism is of great interest to the pharmaceutical industry because polymorphs have different physicochemical properties such as dissolution rate. In the present work, the influence of process conditions on the polymorphic antisolvent crystallization and transformations during cooling crystallization of agomelatine metastable form X from water...
Article
The ability to undergo a transition between dispersed or single-cellular state and aggregated or multi-cellular state provides distinct evolutionary advantages to many natural organisms. Due to a change of hydrodynamic diameter over several orders of magnitude and associated change of fluid–particle interaction (settling velocity) or intra-particle...
Article
This work focuses on the content non-homogeneity in granules across size classes in a high shear wet granulation process as a result of powder segregation during dry mixing coupled with preferential wettability of one of the ingredients with the binder fluid.A two component API-excipient system comprised of acetaminophen (APAP) and microcrystalline...
Article
The vapour-phase dehydration of ethanol over alumina has been considered as a model system for demonstrating a novel concept for the “remote control” of an endothermic catalytic reaction. Control of the reaction rate was achieved by forming composite catalyst pellets consisting of porous alumina with embedded metal (Fe) microparticles. Exposing suc...
Article
The robustness and parametric sensitivity of a high-shear wet granulation process during scale-up was investigated for a formulation containing over 50 % by weight of a hydrophobic Active Pharmaceutical Ingredient (API). The sensitivity of granule properties such as particle size distribution, bulk density and dissolution rate with respect to both...
Article
Control of biochemical reactions in living cells is based on the principle of compartmentalization, whereby the access of substrates to the active sites of enzymes is regulated by the structure of organelles with semi-permeable membranes. The present work describes the fabrication of synthetic microparticles with a similar functionality and the pos...
Article
The dissolution mechanism of a poorly aqueous soluble drug from amorphous solid dispersions was investigated using a combination of two imaging methods: attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopic imaging and Magnetic Resonance Imaging (MRI). The rates of elementary processes such as water penetration, polymer sw...
Article
Many active pharmaceutical ingredients (APIs) are poorly soluble and therefore poorly bioavailable. Advances in crystal engineering have motivated research into the design of pharmaceutical co-crystals. This study examines the formation of agomelatine - citric acid co-crystal in a batch cooling crystallization. Three linear cooling profiles (10 °C,...