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A fully waterborne epoxy system was prepared from waterborne sorbitol-based epoxy resin cured with an alkylated polyalkylene polyamine hardener. The flame-retardant property was accomplished by the application of different additive phosphorous flame retardants (FRs). Phosphonate polyol and ethyl ethylene glycol phosphate which are in the liquid phase, and two FRs in the form of fine-grained particles; aluminium diethyl phosphinate (AlPi), ammonium polyphosphate (APP). The flame-retardant epoxy resin blends were prepared at the same levels of phosphorus content. The results are very promising as the self-extinguishing behaviour was observed at 3%P for all the investigated FRs and at 1%P in the case of APP. Limiting oxygen index (LOI) values were practically good for all FRs and extremely improved in the case of APP. LOI was 48% for the APP sample at 3%P content. Furthermore, this blend showed the best results in the forced flaming conditions as the total heat release in cone calorimetry measurements (THR) decreased by 43% and the peak of heat release rate (pHRR) decreased by 65% with more elongated burning compared to the reference SPE matrix. The efficient solid-phase FR effect of APP was confirmed by scanning electron microscopic (SEM) and attenuated total reflection-infrared spectrometry (ATR-IR) analysis of the residual char after cone calorimetry measurements.

The overview of the literature reveals the lack of comprehensive study on the effect of clay minerals in flame-retarded polylactic acid (PLA) composites. This research focuses on sepiolite (SEP) and montmorillonite (MMT) clay minerals and their impact on ammonium polyphosphate (APP)-based intumescent flame-retardant (IFR) system in PLA. The effects of the clay mineral types, their surface modification (O-SEP and O-MMT, respectively) and their concentration in PLA/APP composites on the flame-retardant properties were comprehensively evaluated through thermal and flammability tests. Overall, the sepiolite-containing samples showed the greatest decrease in pHRR and THR values at the 3 m/m% loading level. The sepiolites showed stronger interfacial interactions with the PLA matrix than the montmorillonites, and the organomodification proved to improve the compatibility of both types of clay minerals according to the dynamic mechanical analysis (DMA) results. Yet, the organomodification had a contradictory effect on the flame-retardant properties. In the case of sepiolites, it proved to be beneficial as the O-SEP added composite achieved a 60% decrease in the pHRR value and reduced the THR value to 60%. For montmorillonites, the improved compatibility by the organomodification with the PLA matrix seemed to hinder its flame-retardant effectiveness, as the critical point to its flame-retardant mechanism is the rapid migration and accumulation of the clay minerals towards the surface of the polymer.

Supercritical CO2-assisted extrusion technique was used to produce flame retarded foams from recycled poly(ethylene terephthalate) (rPET). Synergistic combination of aluminium-alkylphosphinate flame retardant (FR) and natural montmorillonite (MMT) was utilised to provide adequate flame retardancy at moderate loadings, i.e. with less than 9% of additives. Addition of FR was found to increase the rate of degradation during production (compounding and foam extrusion), which was effectively compensated by chain extender (CE) addition that ensured the melt strength required to obtain proper foam structure. The effects of the FR content and the CE addition on the viscosity of the rPET compounds and on the morphological, thermal, flammability and mechanical properties of the foam products were comprehensively investigated. When compared to injection moulded bulk materials of identical compositions, the highly porous structure of foams was found to increase flammability according to UL94 tests and LOI measurements but has not been shown to be detrimental to heat release rates as measured by cone calorimetry. It was concluded that with well-balanced composition, i.e. 8% FR + 1% MMT + 1% CE, low-density foams (with porosities higher than 70%) of uniform microcellular structure and prominent flame retardant characteristics (such as V0 rating according to UL94 standard, LOI of 28.5% and by 50% reduced peak of heat release rate and by 30% reduced total heat emission) can be manufactured even from rPET.

As polypropylene (PP) has no charring ability on its own due to the lack of hydroxyl functional groups, the flame retardant system needs the addition of carbonizing agent in a relatively great amount. Ammonium-polyphosphate (APP), a conventional flame retardant additive was modified by microencapsulation with a sorbitol-based bioepoxy resin shell to create an intumescent flame retardant system with enhanced charring ability for PP. The flame retardant efficiency of the microencapsulated additive, which contains all the components needed in an effective intumescent flame retardant system, was evaluated in PP matrix at different loadings.When compared to the physical mixture of the component, the microencapsuated form of APP (MCAPP) was found to have improved flame retardant efficiency in PP. The LOI values of the MCAPP containing PP samples increased by 8–11 V/V% besides achieved V-0 classification according to the UL94 test. During cone calorimeter tests, the burning intensity was reduced (peak of heat release rate decreased by 20–35% and shifted in time), increased amount of charred residue was obtained, and based on the calculated Flame Retardancy Index (FRI) “Excellent” fire performance was achieved when MCAPP was used. The improved flame retardant performance is attributed to the effective interaction between the APP core and the readily available carbonizing shell, which promoted the formation of increased amount of char accompanied with improved heat protecting and barrier efficiency.

In this paper we present a thorough description of the digital twin development for a continuous pharmaceutical powder blending process in accordance with the Process Analytical Technologies (PAT) and Quality by Design (QbD) guidelines. A low-dosage system of caffeine active pharmaceutical ingredient (API) and dextrose excipient was examined via continuous blending experiments. Near infrared (NIR) spectroscopy-based process analytics were applied; quantitative evaluation of spectra was achieved using multivariate data analysis. The blending system was represented with mechanistic residence time distribution (RTD) models and two types of recurrent artificial neural networks (ANN), experimental datasets were used for model training or fitting and validation. Detailed comparison of the two modelling approaches, the optimization of the model-based digital twin, and efficiency of the soft sensor-based process monitoring is presented through several validating simulations. Both RTD models and nonlinear autoregressive neural networks demonstrated excellent predictive power for the low dosage blending process. RTD models can prove to be more advantageous in industrial development as they are less resource-intensive to develop and prediction accuracy on low concentration levels lacks dependency from the precision of chemometric calibration. Reduced material costs and limited development timeframe render the digital twin an efficient tool in technological development.

To utilize the effect of probiotics in the oral cavity, an easily applicable, orally dissolving dosage form of Lactobacillus paracasei was prepared by high-speed electrospinning. The scaled-up electrostatic drying technology resulted in high productivity of submicronic, fast-dissolving fibers. To minimize the viability loss of the bacteria, polyvinyl alcohol-polyethylene oxide (PVA-PEO) based polymer systems combined with different stabilizing excipients (glucose, lactose, mannitol, saccharose, trehalose, inulin, and skim milk) were developed. The use of excipients was successful to decrease osmotic and dehydration stress while increasing bacterial survival during electrospinning and long-term storage. The application of trehalose, saccharose, and skim milk as stabilizing excipient, gave 80% or higher bacterial survival during electrospinning; furthermore, in skim milk and mannitol containing formulations 0.5 log unit and 0.2 log unit viability loss was detected after one year. Skim milk showed the best results considering survival rate and long-term stability: after 1 year of storage, a cell count of 7.4 109 CFU/g was measured at 7 °C and 1.56 1010 CFU/g at −20 °C (initial loading was 2.7 1010 CFU/g). Thus, electrospinning using well-selected excipients provides an adequate system that can sustain high-viability of probiotic cells during long-term storage.

Foaming of recycled poly(ethylene terephthalate) (rPET) was performed by supercritical carbon dioxide (sc-CO2) assisted extrusion. The intrinsic viscosity (IV) of rPET was increased from 0.62 dl/g to 0.87 dl/g using an epoxy-functional chain extender, which provided adequate rheological properties for cell stabilization so that an apparent density of less than 0.15 g/cm3 became achievable. Homogeneous and talc induced heterogeneous crystal and cell nucleation, subsequent cell growth and stabilization processes were examined using differential scanning calorimetry (DSC) and scanning electron microscopy (SEM), respectively. It was found that using talc the crystallization temperature increases which results in smaller cell size distribution. A strong correlation was evinced between the apparent density and the Fourier transform near-infrared (NIR) spectrum of the foamed rPET samples enabling quick and non-destructive characterization. Accordingly, NIR spectroscopy is demonstrated as a suitable method for in-line quality monitoring during extrusion foaming of recycled PET, being especially prone to quality fluctuations.

In this study, a robust continuous antisolvent crystallization method was developed to produce the hydrate form of spironolactone. Continuous crystallizations were implemented in a one-stage mixed-...

Innovation in the pharmaceutical industry has been limited for a long time to the research and development of new active compounds; meanwhile, the structure of the production, dominated by batchwis...

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.

Flame retardancy and mechanical performance of multi-layered biocomposites, consisting of polylactic acid (PLA) matrix films and plain-woven flax fabrics as reinforcement, were investigated. Full factorial design (32) was applied to evaluate the effects of the distribution of P and N containing compounds between the matrix and the fibrous carrier. Composition property correlations of the composite constituents (i.e. flax fabrics treated in aqueous solutions of diammonium phosphate and urea with differing ratio and concentrations and matrix films with 0 to 20 wt% ammonium polyphosphate based intumescent flame retardant content) were determined by thermogravimetric analyses and open flame tests. Positive interaction between the composite constituents was revealed for green composites consisting of various combinations of treated fabrics and intumescent PLA systems. The biocomposites flame retarded with a combined approach, i.e. with a balanced distribution of P containing additives between the phases, were found to gain improved mechanical performance and fire retardancy. It was confirmed by tensile testing and electron microscopy as well as by UL-94, limiting oxygen index and cone calorimeter tests. As a conclusion, interpretation is given for the optimum found.

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...

Homogeneous ultralow-dose (30 mg) tablets were prepared from perfectly free-flowing granules manufactured by continuous Twin-Screw Wet Granulation. The gravimetrically fed mixture of lactose and potato starch of low particle size was successfully agglomerated and the size enlargement technology proved to be very robust. Since the incorporated drug was dissolved in ethanol-based granulation liquid, the resulting homogeneity largely depended on the dosing of the applied liquid administering units.A peristaltic pump generated higher deviation of the drug content in tablets (Relative Standard Deviation (RSD): 7.7 %) compared to a syringe pump (RSD: 2.3 %) or a piston pump (RSD: 4.6 %). This is due to the pulsation of the liquid flow generated by the peristaltic pump according to the real-time measured mass of the fed liquid. A good correlation was found between the RSD of the liquid mass flow (calculated from the recorded masses) and the RSD of the drug content. Based on the results, the goodness of Content Uniformity, as the most relevant critical quality attribute of low-dose products, was determined by the characteristics of the applied dosing units. The feeding characteristic of the different pumps could be easily measured by the introduced balance-based method and therefore, the applicability of the pumps could be evaluated.

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.

Curcuminoids (CUs) of antitumor and various other potential biological activities have extremely low water solubility therefore special formulation was elaborated. New fast dissolving reconstitution dosage forms of four CUs were prepared as fibrous form of 2-hydroxypropyl-β-cyclodextin (HP-β-CD). In the electrospinning process HP-β-CD could act both as solubilizer and fiber-forming agent. The solubilization efficiency of the CU-HP-β-CD systems was determined with phase-solubility measurements. The electrospun CUs were amorphous and uniformly distributed in the fibers according to XRD analysis and Raman mappings. The fibrous final products had fast (5 min) and complete dissolution. In typical iv. infusion reconstitution volume (20 mL) fibers containing 40-80 mg of CU could be dissolved, which is similar to the currently proposed dose (120 mg/m

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.

The goal of this paper is to give an introduction to analysis of images acquired by a digital camera with visible illumination and to review its applications as a Process Analytical Technology (PAT) which has great potential in pharmaceutical manufacturing. By utilizing in-line analytical techniques, it is possible to monitor the quality of all the material leaving a processing unit and to create models capable to predict product quality attributes, which are otherwise measured by cumbersome off-line techniques. The rapidly developing machine vision has proven its versatility in numerous applications and it has great potential as an in-line analytical tool. The ongoing conversion of the pharmaceutical industry from batch to continuous manufacturing accelerated the development of digital image analysis methods in the last decade. Among numerous other benefits, continuous technologies, equipped with digital image analysis, enable detecting disturbances in the material flow, and analyzing the products comprehensively. The purpose of this work is to give an insight into the currently available image analysis methods in the characterization of powders, crystallization, granulation, milling, mixing, tableting, film coating, in vitro dissolution testing, and residence time distribution measurements by highlighting some of the most relevant examples of application.

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.

Solid formulations of monoclonal antibodies present several advantages, such as improved stability and increased shelf-life as well as simpler storage and transportation. In this study, we present a gentle drying technology for monoclonal antibodies, applying the water soluble 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) as matrix, to prepare a solid reconstitution dosage form. High-speed electrospinning of an aqueous infliximab-containing HP-β-CD solution was carried out at 25 °C resulting in fibers with an average diameter of 2.5 μm. The mAb-loaded electrospun fibers were successful to preserve the stability of infliximab in solid form. The results of size exclusion chromatography and gel electrophoresis indicated no significant increase in aggregate formation during the electrospinning process compared to the initial matrix solution. The binding activity of infliximab was preserved during electrospinning compared to the reference liquid formulation. Due to the enhanced surface area, excellent reconstitution capability, i.e. clear solution within 2 min without any vigorous mixing, could be achieved in a small-scale reconstitution test. The results of this work demonstrate that high-speed electrospinning is a very promising technique to manufacture the solid formulation of monoclonal antibodies for applications such as fast reconstitutable powders.

Highly homogeneous low-dose (50 μg) tablets were produced incorporating perfectly free-flowing granules prepared by a fully integrated Continuous Manufacturing (CM) line. The adopted CM equipment consisted of a Twin-Screw Wet Granulator (TSWG), a Continuous Fluid Bed Dryer (CFBD) and a Continuous Sieving (CS) unit. Throughout the experiments a pre-blend of lactose-monohydrate and corn starch was gravimetrically dosed with 1 kg/h into the TSWG, where they were successfully granulated with the drug containing water-based PVPK30 solution. The wet mass was subsequently dried in the CFBD on a vibratory conveyor belt and finally sieved in the milling unit. Granule production efficiency was maximized by determining the minimal Liquid-to-Solid (L/S) ratio (0.11). Design of Experiments (DoE) were carried out in order to evaluate the influence of the drying process parameters of the CFBD on the Loss-on-Drying (LOD) results. The manufactured granules were compressed into tablets by an industrial tablet rotary press with excellent API homogeneity (RSD 3%). Significant scale-up was realized with the CM line by increasing the throughput rate to 10 kg/h. The manufactured granules yielded very similar results to the previous small-scale granulation runs. API homogeneity was demonstrated (RSD 2%) with Blend Uniformity Analysis (BUA). The efficiency of TSWG granulation was compared to High-Shear Granulation (HSG) with the same L/S ratio. The final results have demonstrated that both the liquid distribution and more importantly API homogeneity was better in case of the TSWG granulation (RSD 1.3% vs. 4.5%).

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).

The use of Process Analytical Technology tools coupled with chemometrics has been shown great potential for better understanding and control of mammalian cell cultivations through real-time process monitoring. In-line Raman spectroscopy was utilized to determine the glucose concentration of the complex bioreactor culture medium ensuring real-time information for our process control system. This work demonstrates a simple and fast method to achieve a robust partial least squares calibration model under laboratory conditions in an early phase of the development utilizing shake flask and bioreactor cultures. Two types of dynamic feeding strategies were accomplished where the multi-component feed medium additions were controlled manually and automatically based on the Raman monitored glucose concentration. The impact of these dynamic feedings was also investigated and compared to the traditional bolus feeding strategy on cellular metabolism, cell growth, productivity, and binding activity of the antibody product. Both manual and automated dynamic feeding strategies were successfully applied to maintain the glucose concentration within a narrower and lower concentration range. Thus, besides glucose, the glutamate was also limited at low level leading to reduced production of inhibitory metabolites, such as lactate and ammonia. Consequently, these feeding control strategies enabled to provide beneficial cultivation environment for the cells. In both experiments, higher cell growth and prolonged viable cell cultivation were achieved which in turn led to increased antibody product concentration compared to the reference bolus feeding cultivation.

The effect of different frequencies and waveforms was investigated for the first time on alternating current electrospinning (ACES). PVPVA64, a polyvinylpyrrolidone-vinyl acetate copolymer was selected for the experiments as an important matrix for amorphous solid dispersions but never processed with ACES. It has been proved that ACES could be operated in a wide range of frequencies (40–250 Hz) and using different waveforms (sinusoidal, square, triangle, saw tooth) without significant changes in fiber morphology. Nevertheless, deterioration of the fiber formation process could be also observed especially at high frequencies. The developed PVPVA64-based fibers containing small amounts of additives (polyethylene oxide (PEO) and sodium dodecyl sulfate (SDS)) served as an excellent carrier for spironolactone (SPIR), a poorly soluble antihypertensive drug. As a result of the amorphously dispersed SPIR and the large surface area of the AC electrospun fibers immediate drug release could be achieved.

The flame retardancy of sorbitol-based epoxy resin is targeted. From the bioepoxy 3% phosphorus-containing matrix samples were prepared. Surprisingly, only HB classification of UL-94 test was reach...

An innovative, Raman spectroscopy-based monitoring and control system is introduced in this paper for designing dynamic feeding strategies that allow the maintenance of key cellular nutrients at an ideal level in Chinese hamster ovary cell culture. The Partial Least Squares calibration models built for glucose, lactate and 16 (out of 20) individual amino acids had very good predictive power with low root mean square errors values and high square correlation coefficients. The developed models used for real-time measurement of nutrient and by-product concentrations allowed us to gain better insight into the metabolic behavior and nutritional consumption of cells. To establish a more beneficial nutritional environment for the cells, two types of dynamic feeding strategies were used to control the delivery of two-part multi-component feed media according to the prediction of Raman models (glucose or arginine). As a result, instead of high fluctuations, the nutrients (glucose together with amino acids) were maintained at the desired level providing a more balanced environment for the cells. Moreover, the use of amino acid-based feeding control enabled to prevent the excessive nutrient replenishment and was economically beneficial by significantly reducing the amount of supplied feed medium compared to the glucose-based dynamic fed culture.

Recycled polyethylene-terephthalate (RPET) bottle regrinds were physically foamed after two types of industrially feasible molecular weight increasing processes. Intrinsic viscosity (IV) of initial waste (0.71 dL/g) increased both after reactive extrusion carried out using a multifunctional epoxy-based chain extender (0.74 dL/g) and after solid state polycondensation (SSP) (0.78 dL/g), while capillary rheometry revealed higher degree of branching in the chain extended PET material. Despite the relatively low IV values (below 0.80 dL/g), physical foaming, a mild and cost-efficient way, was successful in both cases, uniform microcellular foam structures with void fractions ranging between 75 and 83% were achieved. During the experiments morphology change in the materials was tracked by differential scanning calorimetry (DSC) besides recording IV values. The IV drop during foaming was between 0.03 and 0.10 depending on the pre-processing technology. Structure of foams produced from the two different modified RPET materials was compared with each other based on scanning electron microscopic imaging of cryogenic fracture surfaces. The average cell diameters were measured to be 213 and 360 µm in the case of chain extended and SSP-modified materials, respectively.

Small angle X-ray scattering (SAXS) and polarized Raman spectroscopy were used to examine the structure of unidirectional all-polypropylene composites prepared at different consolidation temperatures. Analysis of the anisotropy of the X-ray scattering pattern provided a way to quantify the disorientation of the crystallites and a direct correlation has been found between a measure of overall orientation and the Young’s modulus of the composites. In the case of the Raman spectroscopic measurements, the molecular orientation state of the reinforcing PP fibres were evaluated by classical least squares (CLS) modelling with real reference spectra. Strong correlation was evinced between the estimated relative degree of orientation of the reinforcing fibres and the Young’s modulus of the multi-layered all-polypropylene composites. Based on these results, both SAXS and Raman spectroscopy are suitable methods to predict the mechanical performance of all-polymer composites, being especially sensitive to manufacturing and application conditions, in a non-destructive way.

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.