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This research aimed to compare two solvent-based methods for the preparation of amorphous solid dispersions (ASDs) made up of poorly soluble spironolactone and poly(vinylpyrrolidone-co-vinyl acetate). The same apparatus was used to produce, in continuous mode, drug-loaded electrospun (ES) and spray-dried (SD) materials from dichloromethane and ethanol-containing solutions. The main differences between the two preparation methods were the concentration of the solution and application of high voltage. During electrospinning, a solution with a higher concentration and high voltage was used to form a fibrous product. In contrast, a dilute solution and no electrostatic force were applied during spray drying. Both ASD products showed an amorphous structure according to differential scanning calorimetry and X-ray powder diffraction results. However, the dissolution of the SD sample was not complete, while the ES sample exhibited close to 100% dissolution. The polarized microscopy images and Raman microscopy mapping of the samples highlighted that the SD particles contained crystalline traces, which can initiate precipitation during dissolution. Investigation of the dissolution media with a borescope made the precipitated particles visible while Raman spectroscopy measurements confirmed the appearance of the crystalline active pharmaceutical ingredient. To explain the micro-morphological differences, the shape and size of the prepared samples, the evaporation rate of residual solvents, and the influence of the electrostatic field during the preparation of ASDs had to be considered. This study demonstrated that the investigated factors have a great influence on the dissolution of the ASDs. Consequently, it is worth focusing on the selection of the appropriate ASD preparation method to avoid the deterioration of dissolution properties due to the presence of crystalline traces.

Crystallization as the most widespread purification, separation, and morphology-determining method is a critical technology that could be made safer and more economical by using continuous crystall...

The present paper reports the powder filling of milled electrospun materials in vials, which contained voriconazole and sulfobutylether-β-cyclodextrin. High-speed electrospinning was used for the production of the fibrous sample, which was divided into 6 parts. Each portion was milled using different milling methods and sizes of sieves to investigate whether the milling influences the powder and filling properties. Bulk and tapped density tests, laser diffraction and angle of repose measurements were applied to characterize the milled powders, while a vibratory feeder was used for the feeding experiments. The correlation between the material property descriptors and the feeding responses was investigated by multivariate data analysis. Based on the results, three samples were chosen for the vial filling, which was accomplished with 3400 mg electrospun material containing 200 mg voriconazole, representative of the commercial product. The feed rate was set to fit the 240 g/h production rate of the electrospinning and the relative standard deviation of three repeated vial filling was determined to see the accuracy of the process. This research shows that by applying a suitable milling method it is possible to process electrospun fibers to a powder, which can be filled into vials and used as reconstitution dosage forms.

This research concentrates on the marked discrepancies in the crystalline structure of poly(lactic acid) (PLA) nano- and microfibres, achieved by different annealing strategies. PLA nonwoven mats were produced by high-speed electrospinning. The high-speed production technique allowed the manufacturing of PLA microfibres with diameters of 0.25–8.50 µm with a relatively high yield of 40 g h−1. The crystalline content of the inherently highly amorphous microfibres was increased by two methods; thermal annealing in an oven at 85 °C was compared to immersion in absolute ethanol at 40 °C. The morphology of the fibres was examined by scanning electron microscopy; crystalline forms and thermal properties were assessed using X-ray diffractometry, Raman spectrometry, differential scanning calorimetry (DSC) as well as modulated DSC. As a consequence of 45-min heat treatment, the crystalline fraction increased up to 26%, while solution treatment resulted in 33% crystallinity. It was found that only disordered α′ crystals are formed during the conventional heat treatment; however, the ethanol-induced crystallization favours the formation of the ordered α polymorph. In connection with the different crystalline structures, noticeable changes in the macroscopic properties such as heat resistance and mechanical properties were evinced by localized thermomechanical analysis and static tensile test, respectively.

The aim of this study was to develop a new, easily performable feedback control of crystallization based on the exact polymorphic concentration (mass ratio of polymorph/solvent). The efficiency of the developed process control, utilizing combined signals of inline Raman and attenuated total reflectance ultraviolet visible sensors, was tested in a cooling crystallization of carvedilol. The solution concentration was determined according to multivariate calibration results of UV/vis spectroscopic detection, while the evaluation of the composition of the solid phase was performed by means of Raman spectroscopy assisted by the classical least-square method resulting in spectral concentrations. Polymorphic concentrations were obtained by calculating the current solid phase concentration from UV/vis data, and then this value was proportionated to the Raman spectral concentrations of different polymorphs. The real-time parallel evaluation of Raman and UV spectra was performed with the assistance of a Matlab prog...

In chronic intestinal diseases like inflammatory bowel disease, parenteral administration of biopharmaceuticals is associated with numerous disadvantages including immune reactions, infections, low patient compliance, and toxicity caused by high systemic bioavailability. One alternative that can potentially overcome these limitations is oral administration of biopharmaceuticals, where the local delivery will reduce the systemic exposure and furthermore the manufacturing costs will be lower. However, the development of oral dosage forms that deliver the biologically active form to the intestines is one of the greatest challenges for pharmaceutical technologists due to the sensitive nature of biopharmaceuticals. The present article discusses the various drug delivery technologies used to produce orally administered solid dosage forms of biopharmaceuticals with an emphasis on colon-targeted delivery. Solid oral dosage compositions containing different types of colon-targeting biopharmaceuticals are compiled followed by a review of currently applied and emerging drying technologies for biopharmaceuticals. The different drying technologies are compared in terms of their advantages, limitations, costs and their effect on product stability.

Electrospinning is a technology for manufacture of nano- and micro-sized fibers, which can enhance the dissolution properties of poorly water-soluble drugs. Tableting of electrospun fibers have been demonstrated in several studies, however, continuous manufacturing of tablets have not been realized yet. This research presents the first integrated continuous processing of milled drug-loaded electrospun materials to tablet form supplemented by process analytical tools for monitoring the active pharmaceutical ingredient (API) content. Electrospun fibers of an amorphous solid dispersion (ASD) of itraconazole and poly(vinylpyrrolidone-co-vinyl acetate) were produced using high speed electrospinning and afterwards milled. The milled fibers with an average fiber diameter of 1.6 ± 0.9 µm were continuously fed with a vibratory feeder into a twin-screw blender, which was integrated with a tableting machine to prepare tablets with ~ 10 kN compression force. The blend of fibers and excipients leaving the continuous blender was characterized with a bulk density of 0.43 g/cm3 and proved to be suitable for direct tablet compression. The ASD content, and thus the API content was determined in-line before tableting and at-line after tableting using near-infrared and Raman spectroscopy. The prepared tablets fulfilled the USP content uniformity requirement based on the API content of ten randomly selected tablets. This work highlights that combining the advantages of electrospinning (e.g. less solvent, fast and gentle drying, low energy consumption, and amorphous products with high specific surface area) and the continuous technologies opens a new and effective way in the field of manufacturing of the poorly water-soluble APIs.

In a continuous powder blending process machine vision is utilized as a Process Analytical Technology (PAT) tool. While near-infrared (NIR) and Raman spectroscopy are reliable methods in this field, measurements become challenging when concentrations below 2 w/w% are quantified. However, an active pharmaceutical ingredient (API) with an intense color might be quantified in even lower quantities by images recorded with a digital camera. Riboflavin (RI) was used as a model API with orange color, its Limit of Detection was found to be 0.015 w/w% and the Limit of Quantification was 0.046 w/w% using a calibration based on the pixel value of images. A calibration for in-line measurement of RI concentration was prepared in the range of 0.2−0.45 w/w%, validation with UV/VIS spectrometry showed great accuracy with a relative error of 2.53 %. The developed method was then utilized for a residence time distribution (RTD) measurement in order to characterize the dynamics of the blending process. Lastly, the technique was applied in real-time feedback control of a continuous powder blending process. Machine vision based direct or indirect API concentration determination is a promising and fast method with a great potential for monitoring and control of continuous pharmaceutical processes.

A model anaerobic bacterium strain from the gut microbiome (Clostridium butyricum) producing anti-inflammatory molecules was incorporated into polymer-free fibers of a water-soluble cyclodextrin matrix (HP-β-CD) using a promising scaled-up nanotechnology, high-speed electrospinning. A long-term stability study was also carried out on the bacteria in the fibers. Effect of storage conditions (temperature, presence of oxygen) and growth conditions on the bacterial viability in the fibers was investigated. The viability of the sporulated anaerobic bacteria in the fibers was maintained during 12 months of room temperature storage in the presence of oxygen. Direct compression was used to prepare tablets from the produced bacteria-containing fibers after milling (using an oscillating mill) and mixing with tableting excipients, making easy oral administration of the bacteria possible. No significant decrease was observed in bacterial viability following the processing of the fibers (milling and tableting).

A simple and efficient microwave (MW)-assisted method was elaborated for the catalyst-free synthesis of isoindolin-1-one-3-phosphonates by the three-component condensation of 2-formylbenzoic acid, aliphatic primary amines and various dialkyl phosphites. The batch and the continuous flow reactions were optimized in respect of the temperature, the reaction time and the molar ratio of the starting materials. To evaluate the potential of MW irradiation, comparative thermal experiments were also carried out. In order to obtain &ldquo, real time&rdquo, information about the condensation, the special Kabachnik&ndash, Fields reaction of 2-formylbenzoic acid, butylamine and diethyl phosphite was monitored by in situ FT-IR spectroscopy. The novel title compounds could be prepared in high yields at low temperature under a short reaction time. A suitable method could also be developed for the preparation of the isoindolin-1-one-3-phosphonates at a &ldquo, few g&rdquo, scale by using a continuous flow MW reactor.

The present paper reports the first dynamic image analysis-based feedback control of continuous twin-screw wet granulation process. Granulation of the blend of lactose and starch was selected as a model process. The size and size distribution of the obtained particles were successfully monitored by a process camera coupled with an image analysis software developed by the authors. The validation of the developed system showed that the particle size analysis tool can determine the size of the granules with an error of less than 5 µm. The next step was to implement real-time feedback control of the process by controlling the liquid feeding rate of the pump through a PC, based on the real-time determined particle size results. After the establishment of the feedback control, the system could correct different real-life disturbances, creating a Process Analytically Controlled Technology (PACT), which guarantees the real-time monitoring and controlling of the quality of the granules. In the event of changes or bad tendencies in the particle size, the system can automatically compensate the effect of disturbances, ensuring proper product quality. This kind of quality assurance approach is especially important in the case of continuous pharmaceutical technologies.

The pharmaceutical industry has never seen such a vast development in process analytical methods as in the last decade. The application of near-infrared (NIR) and Raman spectroscopy in monitoring production lines has also become widespread. This work aims to utilize the large amount of information collected by these methods by building an artificial neural network (ANN) model that can predict the dissolution profile of the scanned tablets. An extended release formulation containing drotaverine (DR) as a model drug was developed and tablets were produced with 37 different settings, with the variables being the DR content, the hydroxypropyl methylcellulose (HPMC) content and compression force. NIR and Raman spectra of the tablets were recorded in both the transmission and reflection method. The spectra were used to build a partial least squares prediction model for the DR and HPMC content. The ANN model used these predicted values, along with the measured compression force, as input data. It was found that models based on both NIR and Raman spectra were capable of predicting the dissolution profile of the test tablets within the acceptance limit of the f2 difference factor. The performance of these ANN models was compared to PLS models using the same data as input, and the prediction of the ANN models was found to be more accurate. The proposed method accomplishes the prediction of the dissolution profile of extended release tablets using either NIR or Raman spectra.

Raman spectroscopy as a process analytical technology tool was implemented for the monitoring and control of ethanol fermentation carried out with Saccharomyces cerevisiae. The need for the optimization of bioprocesses such as ethanol production, to increase product yield, enhanced the development of control strategies. The control system developed by the authors utilized noninvasive Raman measurements to avoid possible sterilization problems. Real-time data analysis was applied using partial least squares regression (PLS) method. With the aid of spectral pretreatment and multivariate data analysis, the monitoring of glucose and ethanol concentration was successful during yeast fermentation with the prediction error of 4.42 g/L for glucose and 2.40 g/L for ethanol. By Raman spectroscopy-based feedback control, the glucose concentration was maintained at 100 g/L by the automatic feeding of concentrated glucose solution. The control of glucose concentration during fed-batch fermentation resulted in increased ethanol production. Ethanol yield of 86% was achieved compared to the batch fermentation when 75% yield was obtained. The results show that the use of Raman spectroscopy for the monitoring and control of yeast fermentation is a promising way to enhance process understanding and achieve consistently high production yield.

The goals of this work were to evaluate if high-speed electrospinning can be used as a gentle and continuous drying technology to produce protein-containing cyclodextrin-based fibers from an aqueous solution and to convert the produced protein-cyclodextrin fibers into a directly compressible powder. A 400 mL/h feeding rate was used during the electrospinning experiments, corresponding to a ~270 g/h production rate of the dried material. The produced fibers were collected in a cyclone. The fibers were found grindable without secondary drying, and the ground powder was mixed with tableting excipients and was successfully tableted by direct compression. The model protein-type drug (β-galactosidase) remained stable during each of the processing steps (electrospinning, grinding, tableting) and after 6 months of storage at room temperature in the tablets. The obtained results demonstrate that high speed electrospinning can be a gentle alternative to traditional drying methods used for protein-type drugs, and that tablet formulation is achievable from the electrospun material prepared this way.

The aims of this work were to develop a processable, electrospun formulation of a model biopharmaceutical drug, &beta, galactosidase, and to demonstrate that higher production rates of biopharmaceutical-containing fibers can be achieved by using high-speed electrospinning compared to traditional electrospinning techniques. An aqueous solution of 7.6 w/w% polyvinyl alcohol, 0.6 w/w% polyethylene oxide, 9.9 w/w% mannitol, and 5.4 w/w% &beta, galactosidase was successfully electrospun with a 30 mL/h feeding rate, which is about 30 times higher than the feeding rate usually attained with single-needle electrospinning. According to X-ray diffraction measurements, polyvinyl alcohol, polyethylene oxide, and &beta, galactosidase were in an amorphous state in the fibers, whereas mannitol was crystalline (&delta, polymorph). The presence of crystalline mannitol and the low water content enabled appropriate grinding of the fibrous sample without secondary drying. The ground powder was mixed with excipients commonly used during the preparation of pharmaceutical tablets and was successfully compressed into tablets. &beta, galactosidase remained stable during each of the processing steps (electrospinning, grinding, and tableting) and after one year of storage at room temperature in the tablets. The obtained results demonstrate that high-speed electrospinning is a viable alternative to traditional biopharmaceutical drying methods, especially for heat sensitive molecules, and tablet formulation is achievable from the electrospun material prepared this way.

A family of α-aryl-α-aminophosphonates and α-aryl-α-aminophosphine oxides was synthesized by the microwave-assisted solvent-free addition of dialkyl phosphites and diphenylphosphine oxide, respectively, to imines formed from benzaldehyde derivatives and primary amines. After optimization, the reactivity was mapped, and the fine mechanism was evaluated by DFT calculations. Two α-aminophosphonates were subjected to an X-ray study revealing a racemic dimer formation made through a N–H···O=P intermolecular hydrogen bridges pair.

The development of real-time monitoring and an improved control system was performed according to a process analytical technology initiative focusing on the benefits of the pharmaceutical industry. As an extension of the results of pioneering Raman-based closed-loop feedback control of crystallization and synthesis, a bioprocess, namely, the enzymatic hydrolysis of lactose, was investigated in this work. For this purpose, an effective control system was developed to maintain the lactose concentration at a level of 20 g/L. Real-time evaluation of Raman spectra was accomplished using classical least-squares (CLS) and partial least-squares (PLS) multivariate data analysis methods. Formation of oligosaccharides during the hydrolysis of lactose causes inaccuracy in the CLS evaluation, and thus, optimization of lactose hydrolysis was needed to decrease oligosaccharide formation. After optimization, control of lactose hydrolysis could be achieved. To improve real-time evaluation, the PLS method was used, resulti...

The aims of this study were to evaluate electrospinning as a continuous alternative to freeze drying in the production of a reconstitution injection dosage form, and to prove that aqueous electrospinning can be realized with a high production rate at room temperature. High-speed electrospinning with a novel continuous cyclone collection was used to manufacture a formulation of the poorly water-soluble antifungal voriconazole (VOR) with sulfobutylether-β-cyclodextrin (SBE-β-CD). The freeze-dried, marketed product of this drug substance, Vfend® also contains SBE-β-CD as excipient. SBE-β-CD acted as a ‘quasi-polymer’, and it could be electrospun despite its low molecular mass (2163 Da). According to X-ray diffraction and differential scanning calorimetry, no traces of crystalline VOR were detectable in the fibers. Furthermore, Raman mapping and energy dispersive spectroscopy measurements showed a uniform distribution of amorphous VOR in the fibers. Reconstitution tests carried out with ground fibrous powder showed complete dissolution resulting in a clear solution after 30 s (similarly to Vfend®). The high productivity rate (~240 g/h) achieved using high-speed electrospinning makes this scaled-up, continuous and flexible manufacturing process capable of fulfilling the technological and capacity requirements of the pharmaceutical industry. This work shows that aqueous high-speed electrospinning, being a continuous and high-throughput process, is an economically viable production alternative to freeze drying.

Well designed (multilayer, adaptive, reactive) interphases, being a key element of multicomponent structures, could be tailored to different requirements through controlled technologies. This is the link connecting various green, safe, healthy materials and innovative pharmaceuticals. Upgraded recycling could be performed by interfacial consolidation of self-reinforced composites, the flame retardancy of which is feasible with surprisingly low amount of flame retardant. Examples are shown how the reinforced and foamed forms of thermosetting and thermoplastic biopolymers can play a significant role (after flame retardant modification) in the development of airplanes and electric cars. Biopolymer nanofibres, such as polycaprolactone and polyhydroxybutyrate, could be formed with increased productivity for various medical uses. Raman-based control of the units of integrated continuous technologies has been elaborated including controlled formation of crystals with polymer interlayer for direct tableting.

Although the process analytical technology for ensuring constant product quality and tight control over the manufacturing process, which is especially important in the case of hazardous chemical reactions, has initiated extensive use of real-time spectroscopic methods (ATR-UV/vis, ATR-FTIR, or Raman) for monitoring of chemical reactions, control of chemical syntheses on the basis of inline Raman spectroscopic detection has not been implemented yet. The present paper reports the development of an effective feedback control on the basis of Raman spectroscopy governing a potentially hazardous, exothermic model reaction. The control approach allowed the quantification of reaction components and an unstable intermediate and, furthermore, determined the end point of the reaction. The spectrum of the unstable intermediate was identified using the multivariate curve resolution-alternating least-squares (MCR-ALS) method. The implementation of the feedback control required the development of a program operating the...

Preparation and formulation of amorphous solid dispersions (ASDs) are becoming more and more popular in the pharmaceutical field because the dissolution of poorly water-soluble drugs can be effectively improved this way, which can lead to increased bioavailability in many cases. During downstream processing of ASDs, technologists need to keep in mind both traditional challenges and the newest trends. In the last decade, the pharmaceutical industry began to display considerable interest in continuous processing, which can be explained with their potential advantages such as smaller footprint, easier scale-up, and more consistent product, better quality and quality assurance. Continuous downstream processing of drug-loaded ASDs opens new ways for automatic operation. Therefore, the formulation of poorly water-soluble drugs may be more effective and safe. However, developments can be challenging due to the poor flowability and feeding properties of ASDs. Consequently, this review pays special attention to these characteristics since the feeding of the components greatly influences the content uniformity in the final dosage form. The main purpose of this paper is to summarize the most important steps of the possible ASD-based continuous downstream processes in order to give a clear overview of current course lines and future perspectives.

Multilayer self-reinforced polypropylene composites, fire retarded with APP based intumescent systems, were found to have surprisingly good fire retardancy. The combination of V-0 classification with excellent mechanical properties could be realized at significantly lower additive levels than expected. Modifying the structure of the composites allowed the mechanism behind the observed synergistic effect to be understood. The outstanding efficiency recorded can be explained by the beneficial physical cooperation between the expanding process caused by intumescent fire retardants and the shrinking of the reinforcing tapes. Polymer systems with these components, when exposed to heat, form a special, compact charred surface layer, which hinders the release of pyrolysis gases and where the flame retarding action of P- and N- containing compounds occurs at smaller volume, and thus at higher concentration, resulting in effective fire extinction. The observed novel synergism is promising to be efficiently utilized in the formation of cost-effective, fire retardant, self-reinforced composites.

This study indicates that real-time Raman spectroscopy is more than just an effective tool for monitoring drug crystallizations. The results verify that fibre-optic-coupled Raman spectroscopy can be used not only for monitoring processes but also for ensuring the production of the desired polymorphs by continuous feedback of the polymorph signal in the course of crystallization procedures. Cooling crystallization of an active pharmaceutical ingredient was performed to test the feedback method, during which the kinetically preferred and desired Form II crystal structure was produced. If, however, a thermodynamically stable undesired polymorph is present as an impurity, it will influence the characteristics of the end product. The aim of the control, based on Raman-signal feedback, was to ensure that the quality of the drugs was maintained in crystallization processes, despite such disturbing influences. The feedback control was based on the development of communication between a Raman spectroscope and a pr...

The Kabachnik–Fields reaction of benzaldehyde, cyclohexylamine, and dimethyl phosphite carried out at 80°C in acetonitrile takes place via an imine (PhCNcHex) intermediate, as the monitoring by in situ Fourier transform IR spectroscopy suggested. The corresponding α-hydroxyphosphonate was also formed in a quantity of 13% that was not converted to α-aminophosphonate under the conditions applied. The outcome was similar to the Kabachnik–Fields reaction with diethyl phosphite as the P-component. Molecular modeling and subsequent DFT calculations carried out under solventless conditions supported the experimental results and indicated the formation of a high number of ideally positioned H bonds as the key determinant for the conformation of the starting, intermediate, and product states. The relative energies of the possible intermediates were in accord with the observation that the formation of the α-hydroxyphosphonate is a “dead-end” route. © 2011 Wiley Periodicals, Inc. Heteroatom Chem 23:171–178, 2012; View this article online at wileyonlinelibrary.com. DOI 10.1002/hc.20767

A variety of reactions including esterifications, alkylations, additions, cycloadditions, fragmentations, and condensations were carried out under microwave MW-assisted and solventless conditions, occasionally in ionic liquids (ILs). In a few cases, MW was synergic with phase transfer catalysis or could substitute it. A variety of P(III) ligands were developed and converted to Pt(II) complexes that can be used as catalysts. Finally, phosphorylations and the Kabachnik–Fields reaction were monitored and optimized by an on-line method, in situ Fourier transform IR spectroscopy.

The phospha-Mannich condensation of benzaldehyde, n-propylamine, and diethyl phosphite carried out at 80°C in acetonitrile takes place via the imine (PhCNPr) intermediate as suggested by in situ FT-IR spectroscopy. © 2011 Wiley Periodicals, Inc. Heteroatom Chem 22:599–604, 2011; View this article online at wileyonlinelibrary.com. DOI 10.1002/hc.20676

The reaction of 4-chlorophenol and 4-nitrophenol with diethyl chlorophosphate carried out in a liquid–liquid and solid–liquid two phase system, respectively, was monitored by in situ Fourier transform IR spectroscopy.

In situ Fourier transform IR spectroscopy has been found to be an appropriate tool for monitoring the title reaction resulting in the formation of diethyl phenylphosphate.

In situ Fourier transform IR spectroscopy was a useful tool in monitoring the pH-dependent and two-step oximation of methyl ethyl ketone and benzaldehyde in a liquid–liquid two-phase system, one phase of which was water. Carrying out the oximations at pH 8, the oximation was complete within 45 min and the corresponding carbonyl compound–hydroxylamine adduct (2) could be detected as an intermediate, but at pH 10, the corresponding oxime (3) was formed faster, practically without the appearance of the intermediate. At pH ∼ 2.5 using methyl ethyl ketone, the protonated form of the corresponding oxime (3'a) developed gradually without the transient appearance of the intermediate (2). pH dependence of the 3a → 3'a and 3'a → 3a interconversions were studied in separate experiments.

In situ Fourier transform IR spectroscopy has been found to be an appropriate tool for the evaluation, monitoring and optimization of the pH dependent and two-step oximation of acetone in water. When carrying out the reaction at 5 °C, the intermediate formation of the acetone-hydroxylamine adduct (2) was observed at pH 8.5, while at pH 10, the oxime (3) was formed almost instantly. Identification of the intermediate (2) was promoted by the IR spectrum obtained by B3LYP/6-31++G(d,p)//PCM calculations. At pH ∼ 2.5, the protonated form of the oxime (3') developed gradually, but the intermediate (2) could not be observed. The pH dependence of the stability of the intermediate (2) and the (3' → 3) and (3 → 3') interconversions were studied in separate experiments. An equilibrium was observed in the latter case.

The flame retardant effect of newly synthesized phosphorus-containing reactive amine, which can be used both as crosslinking agent in epoxy resins and as a flame retardant, was investigated. The effect of montmorillonite and sepiolite additives on the fire induced degradation was compared to pristine epoxy resin. The effect of combining the organophosphorous amine with clay minerals was also studied. It could be concluded that the synthesized phosphorus-containing amine, TEDAP can substitute the traditional epoxy resin curing agents providing additionally excellent flame retardancy: the epoxy resins flame retarded this way reach 960 °C GWFI value, 33 LOI value and V-0 UL-94 rating – compared to the 550 °C GWFI value, 21 LOI value and “no rate” UL-94 classification of the reference epoxy resin. The peak of heat release was reduced to 1/10 compared to non-flame retarded resin, furthermore a shift in time was observed, which increases the time to escape in case of fire. The flame retardant performance can be further improved by incorporating clay additives: the LOI and the HRR results showed that the optimum of flame retardant effect of clay additives is around 1 mass% filler level in AH-16–TEDAP system. Applying a complex method for mechanical and structural characterization of the intumescent char it was determined that the flame retarded system forms significantly more and stronger char of better uniformity with smaller average bubble size. Incorporation of clay additives (owing to their bubble nucleating activity) results in further decrease in average bubble diameter.

In this work we aimed at forming partially recycled polymer composites of appropriate mechanical properties and flame retardancy. Multilayer composite structures proved to be suitable to fulfill all of these requirements. Core-shell structures presented here contain two-component thermosets, i.e. epoxy, recycled polyurethane and polyisocyanurate, as matrices reinforced with waste fillers such as short basalt fibers and wood chips. Flame retardancy and mechanical properties of the core-shell structures were investigated by the conventional methods of characterization. The developed cost-effective multilayer composites can be applied as heat and sound insulating panels e.g. multifunctional sheets for construction or automotive industry.

Simple method is proposed for in situ formation of nanodispersion through computer-controlled emulsion polymerization. The method is based on the application of cationic emulsifier during polymerization, which performs cation exchange with the surface Na ions of montmorillonite nanoparticles. The endpoint of polymerization is detected by Raman microscopy while the structure is determined by atomic force microscopy. The nanodispersion is used in the tablet-coating process. Raman microscopy provides a new non-destructive way for controlling the thickness and uniformity of the coatings during the procedure, while the surface defects can be determined by atomic force microscopy. © 2006 John Wiley & Sons, Ltd.

The deterioration of naturally aged low-density polyethylene (LDPE) film was observed by elongation properties, DSC melting enthalpies and surface geometric characteristics by use of atomic force microscopy (AFM). The decrease of elongation at break under the influence of ageing was in good accordance with the increase of melting enthalpies and both phenomena could be explained by the gradual decrease of molecular mass of the polymer. On the wavy surface with a wavelength range of 10–15 μm, valleys with amplitudes from 160 to 600 nm could be observed by AFM depending on the time of ageing. The increase of deepness of valleys was explained not by the gradual erosion of the degraded surface but by the gradual increase of crystallinity, consequently the gradual shrinking on the surface of the polymer film. The gradual increase of crystallinity in the surface region of the film could be demonstrated by confocal Raman microscopy.

Montmorillonite nanoparticles were found to be inefficient in polypropylene because of the lack of a heat insulating char layer and the decomposition of the compatibilising surfactant layer on their surface. Combination with an ammonium polyphosphate-based intumescent system showed some synergism due to modified rheology. The effect of surface and interface modification was analysed using Raman microscopy and X-ray photoelectron spectroscopy. Forming a heat resistant coating layer of low surface energy around the nanoparticles promotes their migration to the surface and formation of a flexible barrier layer, and thus leads to better performance.

New reactive additives were synthesised and used as interface modifiers in different multicomponent polyolefine systems. The synthesis was carried out in computer-controlled reactor by means of Diels-Alder reaction and condensation. These additives are capable of combining the benefits of dispersing and coupling agents. A part of the synthesised reactive surfactants have also synergistic effect in flame retardant systems. Their surface-active character facilitates the reactive compounding. The undesirable transport processes of stabilisers and components of flame-retardants in polyolefine systems could be effectively controlled by interface modification.

New reactive surfactants (RS) and synergistic reactive surfactants (SRS), containing reactive groups and longer unsaturated apolar hydrocarbon chains have been synthesised and applied in filled and flame-retarded polymer systems, respectively. These additives are capable of reactions with the polymer matrix and the disperse phase as well. The reaction of these compounds with polyolefins was proven on model system by surface analysis, while their reaction with fillers was demonstrated by DSC. The interface modification in filled/reinforced polymer systems and polymer blends resulted in improved mechanical properties, while in pigmented PE it contributed to higher photostability. Furthermore, the efficiency of intumescent flame retardant additives in polyolefins could be enhanced.

Optimal concentration of boroxo siloxane elastomer synergist was determined by LOI and cone calorimetric measurements on ammonium polyphosphate and pentaerythritol containing intumescent flame retardant for polypropylene. The increased viscosity of the melt and plasticity of intumescent char due to boroxo siloxane elastomer could be proved by a thermal scanning rheometric investigation. It is presumed, the increased melt viscosity is created by the product of boroxo siloxane-pentaerythritol, formed during the compound preparation, while the improved char plasticity is the result of product formed at high temperature from boroxo siloxane and ammonium polyphosphate.

Methods for developing different types of organic chemical technologies have been elaborated. It required the building up of a system that integrates the advantages of a reaction calorimeter and a model of industrial controlled reactors. The hardware and software configuration support the transfer of elaborated control programs of reactions from laboratory level to the industrial technology. The results of application are shown through the examples of typical unit processes of organic chemical technologies like alkylation, diazotization and esterification in which economical, environmental and chemical advantages could be realized, respectively.

Pentaerythritol may react with tetraethoxy-silane and ammonium-polyphosphate in flame retarded polyolefins and an interfacial layer can be formed around the ammonium-polyphosphate particles. It is advantageous to study such systems using methods of thermal and surface analysis together.

The flame-retardant efficacy of phosphorus-containing reactive amine hardeners for epoxy resins is well-known; however their synthesis often applies hazardous, objectionable reagents. The aim of this work is to develop an effective synthesis method for the preparation of P-containing amines, which can act as flame-retardant crosslinking agent in epoxy resins. The syntheses and testing of an aliphatic and two aromatic amines are described: curing properties, glass transition temperature, thermal stability, and flame-retardant performance of the amines are studied. On the basis of these results, the scaling-up and the optimization of the synthesis of the phosphorus-containing aliphatic amine hardener in ReactIR™ in situ FTIR apparatus is discussed. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 40105.

Crystallization processes can be evaluated from both kinetic and thermodinamic point of view with real-time analitical methods, effects of production parameters on the final quality can be estimated as well. Consequently there is an increasing emphasis on analytical devices being applicable for real-time detection. Among these techniques Raman spectrometry is advantageously utilizable for real-time monitoring of crystallizations. Impurities can dramatically change the nucleation and crystal growth, thus they can alter the physical and chemical properties of the final product. The use of different additives (polymers;surface active ingredients) in the crystallization step in order to modify the product morphology methodically is a new direction in the scientific literature. This study provides an overview of crystallization processes in the presence of additives as well as a summary concerning the monitoring of the drug crystallizations by real-time Raman spectrometry. Furthermore the effect of polyvinyl-pyrrolidone was examined in the course of cooling crystallization of Donepezil HCl, while the process was monitored by in-line Raman spectrometry.

Addressing the recommendations of the 12 basic lows of green chemistry, the microwave technique was utilized in phospha-Mannich, Diels-Alder and inverse Wittig type reactions, moreover under solventless conditions. In the phase transfer catalysed alkylation of CH-acidic compounds, the quaternary onium salts could be substituted by MW irradiation. The effect of chiral phase transfer catalysts was compared on suitable, potentially enantioselective model reactions. Mono- and bidental P-ligands were developed to make available novel platinum complexes that can be useful as catalysts. Finally, esterifications including diesterifications were studied by in situ Fourier Transform IR spectroscopy.

A new type of interfacial additive has been developed by the authors recently. The molecules of amphiphilic character are capable of forming chemical bonds at both the polar and the apolar sides. These reactive surfactants have been synthesised in a specially designed computer-controlled reactor system. The aim of the development was to combine the advantages of nonreactive surfactants and reactive coupling agents, making possible an in-line reactive interface modification during the compounding process of the polymer system. The characteristics and effects of the synthesised compounds were determined using methods of analytical and colloid chemistry, like Raman microscopy, surface tension, contact angle and rheological measurements.