Hans-Ulrich Moritz

Ultrasmall Biocompatible Nanocomposites: A New Approach Using Seeded Emulsion Polymerization for the Encapsulation of Nanocrystals

We report a novel approach of seeded emulsion polymerization in which nanocrystals are used as seeds. Ultrasmall biocompatible polymer-coated nanocrystal with sizes between 15 and 110 nm could be prepared in a process that avoids any treatment with high shear forces or ultrasonication. The number of nanocrystals per seed, the size of the seeds, and the shell thickness can be independently adjusted. Single encapsulated nanocrystals in ultrasmall nanobeads as well as clusters of nanocrystals can be obtained. Polysorbat-80 was used as surfactant. It consists of poly(ethylene glycol) (PEG) chains, giving the particles outstanding biofunctional characteristics such as a minimization of unspecific interactions.

Modeling of the Suspension Polymerization Process Using a Particle Population Balance

On the basis of a population balance and the kinetic mechanism of free-radical suspension polymerization, a mathematical model of the suspension polymerization process is proposed. The population balance model which describes a mechanism involving the particle size distribution (PSD) in disperse systems leads to an integrodifferential equation. The basic numerical approach of this work is to use the finite-difference-differential technique with the logarithmic scale for particle size. The problem then was reduced to obtaining the numerical solution of a set of nonlinear ordinary differential equations. The numerical solutions were compared to experimental data, such as the reaction conversion which includes the gel effect and the particle size distributions, to yield the model parameters by Marquardts method. The regression demonstrates reasonably good accuracy.

Characterization of the spray drying behaviour of emulsions containing oil droplets with a structured interface

The aim of this study was to characterize the process of atomization and drying of layer-by-layer emulsions containing lecithin (single layer emulsion) and lecithin/chitosan (bilayer emulsion) and the oxidative stability of the microcapsules during storage. For this purpose, the analysis of the emulsion spray droplet size during two-fluid nozzle and rotary atomization was carried out to identify suitable process parameters. The drying behaviour of single and bilayer emulsions was investigated by calculation of the volume flow density during single-droplet drying during acoustic levitation. In spray-dried solid particles, the oxidative stability in the single layer microcapsules was higher than in the bilayer microcapsules. This was partly attributed to lower microencapsulation efficiency in the bilayer microcapsules compared to the single layer microcapsules. Furthermore, it could be shown, that excess chitosan in the bulk carrier matrix affects the free volume elements and thus oxygen diffusion.

Reactor scale-up for polymerization in suspension

Abstract The particle size and its distribution are important values to characterize suspension polymers. Certain conditions must be met if a constant mean particle size and size distribution in the suspension polymer are to be maintained during reactor scale-up. The conditions were investigated on the polymerization of styrene and vinyl-acetate. The influence of important physical data of the two-phase system (interfacial tension, viscosities), of the polymerization conditions (stirring or reaction time, stirrer speed, phase ratio, concentration of initiator), and of the geometry of the reactor (stirrer type, tank diameter) on the main particle size and the particle size distribution of the polymer were determined experimentally. The rules for running geometrically similar reactors derived from the functional relationships found are discussed including the problems arising during scale-up.

Macroporous uniform azide- and alkyne-functional polymer microspheres with tuneable surface area: synthesis, in-depth characterization and click-modification

A series of uniform, macroporous poly(styrene-co-divinylbenzene) microspheres with diameters ranging from 6.6 ± 0.6 to 8.6 ± 0.2 μm was prepared in a multistep procedure involving precipitation polymerization synthesis of polystyrene seed particles, swelling of seed particles with plasticiser and porogen, and polymerization of styrene–divinylbenzene (S–DVB) inside the seed particles. Particles prepared with varying DVB feed ratios had comparable diameters (as evidenced by scanning electron microscopy) with specific surface areas increasing with DVB content from 11 to 467 m2 g−1 (measured by nitrogen adsorption). Residual double bonds were converted into azide functionality (through HBr addition and bromo-azide substitution) or alkyne functionality (Br2 addition followed by double elimination) which allowed for CuAAC-click chemistry conjugation with reagents carrying the respective complimentary alkyne or azide functional groups including the fluorescent dye derivatives 7-nitro-4-(prop-2-ynylamino)benzofuran (NBD-alkyne) and Rhodamine B hexylazide synthesised for this purpose. Efficiency of chemical transformations was determined using a combination of CHN and IC elemental analyses, solid state NMR spectroscopy, FT-IR spectroscopy, Raman spectroscopy, and confocal scanning fluorescence microscopy. Although the respective second steps in each modification route (substitution and elimination) suffered from lower yields (∼35%), porous particles with azide loadings of up to 0.71 mmol g−1 and alkyne loadings of up to 0.78 mmol g−1 were prepared. Confocal laser scanning microscopy on Rhodamine B-labelled microspheres indicated functionalization throughout the particles featuring a core–shell structure with higher functionalization in the outer layer of particles. Results are expected to contribute to the development of advanced, well-defined, macroporous particles with high, chemically accessible surface areas.

A case study of real-time monitoring of solid-state phase transformations in acoustically levitated particles using near infrared and Raman spectroscopy

The objective of this study was to monitor the amorphous-to-crystalline solid-state phase transformation kinetics of the model drug ibuprofen with spectroscopic methods during acoustic levitation. Chemical and physical information was obtained by real-time near infrared (NIRS) and Raman spectroscopy measurements. The recrystallisation kinetic parameters (overall recrystallisation rate constant β and the time needed to reach 50% of the equilibrated level t(50)), were determined using a multivariate curve resolution approach. The acoustic levitation device coupled with non-invasive spectroscopy enabled monitoring of the recrystallisation process of the difficult-to-handle (adhesive) amorphous sample. The application of multivariate curve resolution enabled isolation of the underlying pure spectra, which corresponded well with the reference spectra of amorphous and crystalline ibuprofen. The recrystallisation kinetic parameters were estimated from the recrystallisation profiles. While the empirical recrystallisation rate constant determined by NIR and Raman spectroscopy were comparable, the lag time for recrystallisation was significantly lower with Raman spectroscopy as compared to NIRS. This observation was explained by the high energy density of the Raman laser beam, which might have led to local heating effects of the sample and thus reduced the recrystallisation onset time. It was concluded that acoustic levitation with NIR and Raman spectroscopy combined with multivariate curve resolution allowed direct determination of the recrystallisation kinetics of amorphous drugs and thus is a promising technique for monitoring solid-state phase transformations of adhesive small-sized samples during the early phase of drug development.

Seeded emulsion polymerization of styrene: Determination of particle size by flow field-flow fractionation coupled with multi-angle laser light scattering

Three series of polystyrene latices were synthesized using the stepwise seeded emulsion polymerization technique. For kinetic studies reaction was monitored by means of an isoperibolic calorimeter, and synthesized particles were analyzed by means of flow field-flow fractionation combined with multi-angle laser light scattering and by means of rotational disc centrifugation. Latices were found to be in the range from 77 to 442 nm diameter for the first series and from 53 to 210 nm for the second series. The third series were two mixtures of two latices with diameters of 136 and 204 nm respectively 157 and 232 nm. Particle growth between each step is of the factor 1.244 (first series) respectively 1.212 (second series) and therefore slower than theoretically expected (1.26). The particle size distribution width decreases in relative values as particle size increases.

Synthesis and in-depth characterization of reactive, uniform, crosslinked microparticles based on free radical copolymerization of 4-vinylbenzyl azide

The introduction of functional groups into microparticles is commonly accomplished through, at times, low-yielding post-synthesis modification. In this detailed study, the introduction of azide functionality into uniform, crosslinked, macroporous microparticles through direct copolymerization of styrene, divinylbenzene (DVB), and 4-vinylbenzyl azide (VBA) in varying ratios inside swollen polystyrene seed (template) particles is investigated. Formulations contained up to 40 wt% of VBA in the monomer mixture. Resulting microspheres were characterised by SEM, porosimetry, FT-IR spectroscopy, and CHN elemental analysis. Uniform spherical particles with diameters ranging from 7.3 to 10.8 μm with diameter dispersities typically below 1.01 and with tuneable azide loadings from 0.11 to 1.17 mmol g−1 were obtained. Interestingly, severe effects of VBA addition on porosity, surface smoothness, and particle shape were observed. Specific surface areas and cumulative pore volumes increased with the amount of DVB in feed, decreased with increasing VBA feed ratio, and increased drastically for the use of azide-functional template particles with measured cumulative pore volumes reaching up to 0.60 cm3 g−1. With increasing VBA feed, formation of smaller, secondary particles was observed and attributed to an incomplete swelling of VBA into seed particles, which is discussed as a main reason for lower-than-expected azide contents in product particles. For high VBA feed ratios (>25 wt%), dented, hollow, or hollow collapsed azide-functional particles were found, presumably due to immiscibility of the growing azide-functional copolymer with the polystyrene seeds. Finally, successful click-modification is demonstrated with phenylacetylene and an alkyne-functional Rhodamine B dye allowing for mapping of functionalization density through confocal fluorescence microscopy.

Increased Reactor Performance versus Reactor Safety Aspects in Acrylate Copolymerization

The aim of reducing cycle times of semibatch-polymerization processes requires systematic investigations of the kinetics, careful adjustment of the desired polymer properties, proper thermal reactor design and reliable reactor safety assessment [1]. As a concrete example, a semibatch-copolymerization was carefully examined with respect to four different aspects. Thermo-kinetics of the reaction were investigated with isoperibolic reaction calorimetry and GC. In order to obtain reliable values for the overall heat transfer coefficient of the production scale reactor, cooling experiments were carried out with solvent and final copolymer solution as reactor content. For consistent reactor safety assessment additional investigations are necessary including case studies of breakdown incidences. These simulations were performed with a mathematical model based on the GC data and experimental vapor pressure curves. As a result of these calculations, a reduction of reaction time from 10 to 6 hours was possible. To convert into practice, it must be ensured that even in this shortened time a product of the same quality is produced.

Two in one: use of azide functionality for controlled photo-crosslinking and click-modification of polymer microspheres

Spherical, micrometer-sized, azide-functional particles were produced through dispersion copolymerization of styrene and vinylbenzyl azide (VBA, 1–100 wt% of monomer feed) in ethanol in the presence of stabilizers. The obtained microspheres were characterized by SEM, disc centrifuge, FT-IR and NMR spectroscopy, elemental analysis, DSC, and TGA, had measured azide loadings of up to 5.58 mmol g−1, and average diameters that decreased with increasing azide content from 2.8 to 0.8 μm. Microspheres were irradiated at a wavelength of 254 nm resulting in crosslinking based on azide-to-nitrene decomposition and subsequent C–H insertion and CC addition reactions. The conversion of azide functionality was monitored by FT-IR spectroscopy, elemental analysis, and DSC and was found to roughly follow first-order kinetics with increased rates found for microspheres with lower azide contents. Photo-crosslinking preserved shapes and size distributions and, above a crosslinking degree of 10%, prevented microsphere dissolution in good solvents. By controlling the irradiation time, the amount of azide consumed for photo-crosslinking could be precisely adjusted. Residual azide groups spared during the irradiation were shown to be amenable to highly efficient CuAAC click modification with a fluorescent dye, Rhodamine B propargyl ester. Given the demand for functional crosslinked microspheres and the inherent difficulties associated with common synthetic strategies in producing such materials, this methodology based on two orthogonal chemistries of the azide functionality provides simple access to well-defined microspheres with customizable degrees of crosslinking and functional group densities.