František Štěpánek

Dynamics of chemotactic droplets in salt concentration gradients.

The chemotactic movement of decanol droplets in aqueous solutions of sodium decanoate in response to concentration gradients of NaCl has been investigated. Key parameters of the chemotactic response, namely the induction time and the migration velocity, have been evaluated as a function of the sodium decanoate concentration and the NaCl concentration gradient. The ability of the decanol droplets to migrate in concentration gradients has been demonstrated not only in a linear chemotactic assay but also in a topologically complex environment. Additionally, the ability to reverse the direction of movement repeatedly, to carry and release a chemically reactive cargo, to select a stronger concentration gradient from two options, and to initiate chemotaxis by an external temperature stimulus have been demonstrated.

Investigation of internal microstructure and thermo-responsive properties of composite PNIPAM/silica microcapsules.

Composite microcapsules consisting of a thermo-responsive hydrogel poly-N-isopropylacrylamide (PNIPAM) and coated by silica (SiO(2)) nanoparticles have been synthesized by the inverse Pickering emulsion polymerization method. The composite capsules, whose mean diameter is in the 25-86 microm range in the expanded state, were characterized by static light scattering, atomic force microscopy (AFM), scanning electron microscopy (SEM), and laser scanning confocal microscopy (LSCM). It is reported that the hydrogel surface is uniformly covered by a monolayer of silica nanoparticles and that depending on the capsule size and degree of polymer cross-linking, either hollow-core or partially-filled hydrogel-core microcapsules can be created. Equilibrium thermo-responsive behavior of the composite microcapsules is investigated and it is found that after heating the particles above the lower critical solution temperature (LCST) of PNIPAM, the shrinkage ratio V/V(max) varies from 0.8 to 0.4 for a cross-linking ratio from 0.6% to 9% on a mass basis. Dynamic temperature cycling studies reveal no hysteresis in the shrinking and recovery phases, but a small measurable dependence of the asymptotic shrinkage ratio V/V(max) on the rate of temperature change exists. The composite capsules are stable under long-term storage in both dried and hydrated states and easily re-dispersible in water.

Modeling of Transport and Transformation Processes in Porous and Multiphase Bodies

Abstract A methodology for computer representation of the structure of spatially complex multiphase media and for the modeling of reaction, transport, and structure-transformation processes in those media, is reviewed. The methodology is demonstrated via several examples including phase transition and structure evolution in porous and granular media, the morphogenesis of polymer particles, and heterogeneous catalysis. Several future potential applications of the methodology are identified.

Remotely controlled diffusion from magnetic liposome microgels.

The reversible, temperature-dependent change in the permeability of a phospholipid bilayer has been used for controlling the diffusion rate of encapsulated molecular payload from liposomes. Liposomes were preloaded with a fluorescent dye and immobilized in calcium alginate hydrogel microparticles that also contained iron oxide nanoparticles. The composite microparticles were produced by a drop-on-demand inkjet method. The ability of iron oxide nanoparticles to locally dissipate heat upon exposure to a radio-frequency (RF) alternating magnetic field was used to control the local temperature and therefore diffusion from the liposomes in a contactless way using an RF coil. Several different release patterns were realized, including repeated on-demand release. The internal structure of the composite alginate-liposome-magnetite microparticles was investigated, and the influence of microparticle concentration on the heating rate was determined. In order to achieve a temperature rise required for the liposome membrane melting, the concentration of alginate beads should be at least 25% of their maximum packing density for the nanoparticle concentration and specific absorption rate used.

Dynamics of particle growth and overheating in gas-phase polymerization reactors

The particle overheating is an important problem in the industrial catalytic gas-phase olefin polymerization reactors. It has been first investigated with a pseudo-stationary model of a single polymer particle by Hutchinson and Ray (J. Appl. Poly. Sci. 34 (1987) 657). A systematic study of overheating of polymer particle with models based on Ficks and dusty gas model (DGM) transport described below is conducted by tools of continuation (steady-state) analysis and by dynamic simulations. The consideration of convective flow of species in particle pores driven by pressure gradient due to the change in the number of moles in the course of the polymerization reaction makes the polymer particle in the reaction environment containing only monomer more susceptible to overheating. It is found that an intraparticle mass transport resistance has an important effect on particle overheating. The prediction and discussion of a time-scale of particle overheating under industrial process conditions is coupled with the discussion of the dynamics of particle growth and dynamic changes of catalyst activity.

Investigation of drug-polymer interaction in solid dispersions by vapour sorption methods.

The objective of this study was to investigate the effect of different polymeric carriers in solid dispersions with an active pharmaceutical ingredient (API) on their water vapour sorption equilibria and the influence of the API-polymer interactions on the dissolution rate of the API. X-ray diffraction, scanning electron microscopy (SEM), moisture sorption analysis, infrared (IR) spectroscopy and dissolution tests were performed on various API-polymer systems (Valsartan as API with Soluplus, PVP and Eudragit polymers) after production of amorphous solid dispersions by spray drying. The interactions between the API and polymer molecules caused the water sorption isotherms of solid dispersions to deviate from those of ideal mixtures. The moisture sorption isotherms were lower in comparison with the isotherms of physical mixtures in all combinations with Soluplus and PVP. In contrast, the moisture sorption isotherms of solid dispersions containing Eudragit were significantly higher than the corresponding physical mixtures. The nature of the API-polymer interaction was explained by shifts in the characteristic bands of the IR spectra of the solid dispersions compared to the pure components. A correlation between the dissolution rate and the water sorption properties of the API-polymer systems has been established.

Nanocrystals for dermal penetration enhancement – Effect of concentration and underlying mechanisms using curcumin as model

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. Curcumin nanocrystals were produced by the smartCrystals® process, i.e. bead milling followed by high pressure homogenization. The mean particle size of the curcumin crystals was about 200nm. Stabilization was performed with alkyl polyglycoside surfactants. The distribution of curcumin within the skin was determined in vitro on cross-sections of porcine skin and visualized by fluorescent microscopy. The skin penetration profile was analyzed for the curcumin nanosuspension with decreasing concentrations (2%, 0.2%, 0.02% and 0.002% by weight) and compared to nanocrystals in a viscous hydroxypropylcellulose (HPC) gel. This study demonstrated there was minor difference between low viscous nanosuspension and the gel, but low viscosity seemed to favor skin penetration. Localization of curcumin was observed in the hair follicles, also contributing to skin uptake. Looking at the penetration of curcumin from formulations with decreasing nanocrystal concentration, formulations with 2%, 0.2% and 0.02% showed a similar penetration profile, whereas a significantly weaker fluorescence was observed in the case of a formulation containing 0.002% of curcumin nanocrystals. In this study we have shown that curcumin nanocrystals prepared by the smartCrystal® process are promising carriers in dermal application and furthermore, we identified the ideal concentration of 0.02% nanocrystals in dermal formulations. The comprehensive study of decreasing curcumin concentration in formulations revealed that the saturation solubility (Cs) is not the only determining factor for the penetration. A new mechanism based also on the concentration of the nanocrystals on skin surface was proposed.

Identifying the mechanisms of drug release from amorphous solid dispersions using MRI and ATR-FTIR spectroscopic imaging

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 swelling, growth and erosion of gel layer, and the diffusion, release and in some cases precipitation of drug were evaluated by image analysis. The results from the imaging methods were compared with drug release profiles obtained by classical dissolution tests. The study was conducted using three polymeric excipients (soluplus, polyvinylpyrrolidone - PVP K30, hydroxypropylmethyl cellulose - HPMC 100M) alone and in combination with a poorly soluble drug, aprepitant. The imaging methods were complementary: ATR-FTIR imaging enabled a qualitative observation of all three components during the dissolution experiments, water, polymer and drug, including identifying structural changes from the amorphous form of drug to the crystalline form. The comparison of quantitative MRI data with drug release profiles enabled the different processes during dissolution to be established and the rate-limiting step to be identified, which - for the drug-polymer combinations investigated in this work - was the drug diffusion through the gel layer rather than water penetration into the tablet.

Remotely triggered release from composite hydrogel sponges

A thermoresponsive poly(N-isopropylacrylamide) (PNIPAM) hydrogel crosslinked with methylene bisacrylamide (MBA), with the ability to undergo a volume change of approximately 50%, was used to fabricate a hydrogel “sponge” with oil microdrops encapsulated within its structure by the polymerization of an O/W emulsion. By adding 1.5 wt.% of iron oxide nanoparticles to the hydrogel structure it is possible to trigger the hydrogel volume change remotely by exposing the composite to an alternating magnetic field in the radiofrequency range, which heats up the nanoparticles. The increase of the hydrogel temperature leads to its shrinking and subsequently the encapsulated oil droplets are squeezed out. It was shown that the oil is released gradually during cyclic volume change (repeated heating and cooling) and the amount of oil content released during the first 8–15 shrinking cycles was in the range 1–3% v/v per cycle. The total amount of the released oil phase was in the range 18–24% v/v and it was found to be affected by the size of the encapsulated microdroplets, with the larger ones being squeezed out preferentially.

On the modeling of PSA cycles with hysteresis-dependent isotherms

Abstract A four-step pressure swing adsorption (PSA) process for air drying on a silica gel dessicant is considered. The effects of hysteresis in adsorption/desorption equilibrium isotherms and of loading dependence of the effective diffusion coefficient on the process performance are investigated on a mathematical model. A comparative parametric study reveals that for identical operating conditions, hysteresis can be detrimental to product purity. Multiplicity of cyclic steady states is shown to exist as a result of hysteresis. A transient regime invoked by a gradual change in the inlet air humidity is discussed.