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Two-photon polymerization(2PP) is a process for three-dimensional (3D) micro-and Nano structuring based on the locally controlled curing of liquid precursors (light-sensitive resins) by photochemical triggered polymerization. In this decade, will be hearing a lot about this technic being applied to pharmaceutical applications like fabricating 3D microchannels for nanoparticle precipitation, nano-porous membranes and scaffolds for cell culturing, biomimetic organ-on-chip systems. This paper presents 2pp applied microsystems for continuously generating lipid nanoparticles which are one of the most important drug carrier system. The most important advantages of 2pp is manufacturing 3D shapes that is not possible with lithographic micro and nano fabrication technologies. Also, it will be shown how 2pp fabricated microchannel can be integrated with continuous size measurement by flowDLS for the feed-back controlled generation of nanoparticles., SPhERe Proceedings: 4th International Symposium on Pharmaceutical Engineering Research

Antibiotic resistance is undermining public health; it is imperative that new classes of antibiotics are discovered and developed by companies and academic institutions alike. Previous research by this group used the excellent adaptability of N-heterocyclic carbene (NHC)-silver compounds, which allowed for the discovery of the lead compound 1,3-dibenzyl-4,5-diphenylimidazol-2-ylidene silver(I) acetate (SBC3) [1]. SBC3 breaks the methicillin-resistance in Staphylococcus aureus (MRSA) [2] and has proven effective in in vivo tests using Galleria mellonella [3]. More recently, encouraging parts of the antibiotic mechanism of SBC3 were discovered, which underlines the ability of SBC3 to break antibiotic resistance patterns [4]. And SBC3 was tested successfully against biofilms in vitro and against MRSA in-infected mice in vivo [5]. In addition, a telescoped continuous flow route was developed which surpassed the previous batch approach. This provided for a scalable means to afford the targets in higher yield., SPhERe Proceedings: 4th International Symposium on Pharmaceutical Engineering Research

Understanding powder flow and how it affects pharmaceutical manufacturing process performance remains a significant challenge for industry. This work aims to improve decision making for manufacturing route selection, achieving the key goal of digital design within Industry 4.0 of being able to better predict properties whilst minimizing the amount of material required and time to inform process selection during early-stage development. A Machine Learning model approach is proposed to predict the flow properties of new materials from their physical properties. The model’s implementation will enhance manufacturing quality by taking advantage of the data generated throughout the manufacturing process., SPhERe Proceedings: 4th International Symposium on Pharmaceutical Engineering Research

Poorly separable liquid/liquid mixtures often pose a major challenge in pharmaceutical extraction. In particular, compounds containing a low difference of density are difficult to separate using mixer-settler setups. The Zaiput device can prove an advantage over present liquid/liquid extractors. The research work involves characterizing the Zaiput apparatus for liquid/liquid extraction of pharmaceutical compounds with the model solvent system toluene-water. The extraction efficiency was investigated for a solvent mixture containing toluene-acetone-water residence times. To evaluate the separation success, the outlet’s concentrations are measured via IR spectroscopy., SPhERe Proceedings: 4th International Symposium on Pharmaceutical Engineering Research

The poor solubility of a large number of active pharmaceutical ingredients (API) is a major challenge in pharmaceutical research. Therefore, the extrusion of amorphous solid dispersions (ASDs) is one promising approach to enhance the dissolution rate by molecularly dissolve the API in an amorphous carrier polymer. During ASD development, crucial parameters as the dissolution and the decomposition need to be monitored. Within this study, a small scale twin screw extruder was coupled with special ColVisTec UV-Vis probes that are characterized by their small dimensions. This setup enables a systematic formulation development and optimization based on in-line monitoring of crucial parameters using small amounts of material., SPhERe Proceedings: 4th International Symposium on Pharmaceutical Engineering Research

Spherical agglomeration (SA) is a key crystal shape modification technique commonly used to improve processability and physical properties of active pharmaceutical ingredients (APIs), such as flowability and dissolution. SA involves the introduction of a bridging liquid in the form of droplets into a suspension of API crystals. A novel approach was successfully implemented in this study by adopting a membrane emulsification (ME) system to control the size of bridging liquid droplets and spherical agglomerates. The study investigated ways to achieve the critical quality attributes of the spherical agglomerates by varying operating conditions and design parameters, including mixing rate, bridging liquid injection rate and membrane pore diameter. Antisolvent crystallization of benzoic acid in ethanol (solvent) and water (antisolvent) in presence of toluene as a bridging liquid was used as a case study. Spherical agglomerates of benzoic acid with enhanced quality attributes and mean size of 300 μm were obtained using a membrane pore size of 18 μm, a bridging liquid flow rate of 0.025 mL/min and mixing rate in the range of 800 RPM and 1000 RPM., SPhERe Proceedings: 4th International Symposium on Pharmaceutical Engineering Research

Mixing is a crucial parameter for a wide range of processes in bio-/chemical engineering. In multiphase flows, the aim is a high and uniform mixing effect throughout the reaction volume without negative effects on the discrete phase. These are usually caused by the hydromechanical stress exerted by the mixing element. The present study introduces a novel reactor concept to overcome the use of fast rotating, locally acting mixing elements common in stirred tank reactors. Therefore, the reactor is designed of a flat, horizontally mounted cylinder, which enables mixing of the enclosed volume by its rotation around the central axis. To evaluate the mixing performance, a colorimetric method for mixing time determination is presented and the spatial evolution of mixing kinetics visualized. In addition, the method reveals the dependencies of the mixing time on the rotational speed and filling volume., SPhERe Proceedings: 4th International Symposium on Pharmaceutical Engineering Research

Two-phase biocatalysis is commonly used for the bioconversion of water-insoluble chemical and pharmaceutical compounds. In research laboratories, such processes often take place in flasks and are driven and limited by slow diffusive processes. In this work, we developed droplet-based microfluidic systems and used them to perform testosterone dehydrogenation. The use of microdroplets as reaction vessels offers the advantage of greatly improved diffusion rates due to significantly increased surface-to-volume ratio. We found that indeed reaction time was reduced from tens of minutes to tens of seconds without sacrificing conversion efficiency. This demonstrates the potential of droplet-based two-phase biocatalysis., SPhERe Proceedings: 4th International Symposium on Pharmaceutical Engineering Research

Secondary nucleation is widely present in crystallisation processes and it is often relied upon to attain desirable critical quality attributes of crystalline products, such as polymorphic form and crystal size distribution. This is particularly the case in continuous crystallisation, where a good control of secondary nucleation can be crucial in order to achieve and maintain steady state operation. This work utilises rapid, small-scale experiments in agitated vials with in-situ imaging for crystal counting and sizing (using the Crystalline platform), to quantify nucleation and crystal growth kinetics of α-glycine across a range of supersaturations in aqueous solutions under isothermal conditions. Both seeded and unseeded crystallisation experiments were conducted. It was found that secondary nucleation and crystal growth rates determined from the same vials show a close correlation across the whole range of supersaturations investigated, which suggest a close relationship between the mechanisms of shear induced secondary nucleation and crystal growth in this system., SPhERe Proceedings: 4th International Symposium on Pharmaceutical Engineering Research

Amorphous solid dispersions (ASDs) of a poorly water-soluble active pharmaceutical ingredient (API) in a polymer matrix can enhance the water solubility and improve the bioavailability of the API. Many ASD products are kinetically stabilized, and the inhibition of crystallization of an API within and beyond shelf life is still a matter of debate, since the formation of crystals may impact bioavailability. We present the first literature examples of ASD long-term stability studies over up to 25 years under ambient storage conditions where no API crystallization was observed. Additionally, a risk assessment and mitigation strategy of API crystallization in packaged ASD drug products (DP) is outlined. The risk of shelf-life crystallization and the respective mitigation steps are assigned for different DP development scenarios. Ultimately, the physical stability of ASD DPs during shelf-life storage is modeled by quantifying crystal growth kinetics by transmission Raman spectroscopy (TRS), modeling the impact of water sorption on the glass-transition temperature of the ASD, and predicting the moisture uptake by the packaged ASD DP during storage. This approach is applied to an ASD of an AbbVie-internal compound showing stability beyond the anticipated shelf-life., SPhERe Proceedings: 4th International Symposium on Pharmaceutical Engineering Research

The cryopreservation of cells and tissue engineered constructs is determined by multiple factors, such as possible cellular damages due to mass and heat transfer during the freezing and thawing process. It is assumed that the utilization of cryobags improves the heat transfer during freezing and thawing and is therefore superior in comparison to currently applied cryovials and multiwell plates. Therefore, we have analysed the cryopreservation of cell-seeded electrospun polycaprolactone/polylactide scaffolds within cryobags. Additionally, the performance of four different cryoprotective agents was analysed, which included 10% (v/v) dimethyl sulfoxide and 10% (v/v) ethylene glycol as separately applied agents as well as their combination with 0.3 M sucrose. The samples were frozen in in-house made cryobags with a controlled rate freezer. The cell viability was analysed by fluorescence microscopy before freezing and after thawing. The results show, that the application of cryobags in combination with 10% (v/v) ethylene glycol can have a positive impact onto the cell viability., SPhERe Proceedings: 4th International Symposium on Pharmaceutical Engineering Research

Without any doubt the young technology of additive manufacturing, including 2D and 3D printing, has been changing the world. A wide spectrum of objects in medical and pharmaceutical field can already be successfully printed. This ranges from a detailed figure in the micrometer regime to a full size residential house unit made from concrete [Sakin et al., 2017; Doherty et al., 2020]. In the pharmaceutical sector, additive manufacturing offers the option of medication customization [Pravin et al., 2018]. Integrating this new technology has several advantages over the current, well-established but outdated “one-size-fits-all” approach. Besides avoiding medication errors, printing tailored oral dosage forms is financially attractive for small scale on-demand production [Awad et al., 2018]. The development of dosage forms, production of sample batches and modification of samples can be done with little effort compared to generic powder-pressed pills which require heavy pharmaceutical machinery [Awad et al., 2018; Dachtler et al., 2020]. To further progress and to create the legal framework for the approval of additively manufactured drugs it requires a paradigm change of stakeholders who have the power to make decisions and changes [Horst et al., 2019]., SPhERe Proceedings: 4th International Symposium on Pharmaceutical Engineering Research

In December 2019, a series of pneumonia of unknown cause emerged in Wuhan, China, which developed into a global pandemic with more than 200 million cases and 4 million deaths worldwide as of August 2021. The enveloped RNA betacoronavirus which was found to cause the pandemic was named severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Academia and industry started with non-clinical and clinical development of several SARS-CoV-2 vaccine candidates immediately and results were achieved enormously fast. As an example, BioNTech and Pfizer got their joint SARS-CoV-2 vaccine approved less than eight months after trials started, while under normal circumstances vaccine development takes up to 10 – 15 years. In the case of the SARS-CoV-2 vaccine the extremely fast turnaround time from start of clinical trials to approval of the first vaccine candidates was driven by the urgent medical need and made possible by the mobilisation of enormous financial resources from the private and public sectors, as well as manpower and effort and the willingness of regulators to speed up timelines and approval processes. Looking at the extremely fast and successful development of several SARS-CoV-2 vaccine candidates, it is difficult to understand from a layman’s perspective why for others diseases like Human Immunodeficiency Virus/ Acquired Immunodeficiency Syndrome (HIV/AIDS) and tuberculosis (TB), which are among the top ten causes of death worldwide, development of effective vaccines takes so long. More than 30 years after HIV has been discovered, there is still no vaccine available for prevention of HIV infection. Development of several vaccine candidates has failed in clinical trials. The difficulties stem in large part from HIV’s unusual characteristics of replicating and mutating rapidly and high sequence diversity, its ability of immune system evasion and the creation of a persistent viral reservoir within the host. Development of the novel TB vaccine candidate VPM1002, which is designed to be a safe and effective vaccine for prevention of TB infection and TB recurrence, is an example of classical vaccine development. VPM1002 was invented in Germany, went through successful non-clinical development and is currently being tested in phase III clinical trial. The achievements during the last year fast development of SARS-CoV-2 vaccines during the last year have proven that in case of a pandemic situation and an urgent medical need, fast vaccine development is possible. The achievements were reached with high financial commitment and regulators have shown willingness and engagement to accelerate timelines for review and approval processes. It would be desirable if further vaccine developments could benefit from these efforts., SPhERe Proceedings: 4th International Symposium on Pharmaceutical Engineering Research

Polymerized Ionic Liquids (PILs) are hydrogels synthesized from ionic liquids. They combine the positive characteristics of ionic liquids and polymers which is why they have a wide range of applications, e.g. in the pharmaceutical sector. They are characterized by properties such as high mechanical strength, biocompatibility, and favorable swelling behavior. In this study, the extremely high mechanical strength of novel polymerized ionic liquids (PILs)-based hydrogels was confirmed by mechanical tests. The swelling behavior was studied of hydrogels based on 1-Vinyl-3-alkylimidazolium bromide with different crosslinkers in various solvents – aqueous and organic., SPhERe Proceedings: 4th International Symposium on Pharmaceutical Engineering Research

Encapsulation of clinically relevant cells, such as multipotent stromal cells (MSCs), in three-dimensional (3D) core-shell alginate structures is a promising method for the treatment of various diseases as well as drug testing and development. By utilizing the alginate capsules, drugs and active substances can be delivered specifically to the desired place within the patients’ body. The aim of this work was to investigate the effect of cryopreservation on the integrity of cell-free coaxial alginate capsules after thawing using slow freezing to ensure their long-term storage. Alginate capsules were produced by electro-spraying and cryopreserved using different cryoprotective agents (CPAs), incubation time and thawing temperature. The results suggest that the capsules loaded with 10% (v/v) dimethyl sulfoxide (DMSO) and 0.3 M sucrose and using high thawing rates demonstrated a beneficial effect on the integrity of capsules, as compared to 10% (v/v) DMSO alone and applying low thawing rates. This study is a further development towards the application of cryopreservation for long-term storage and the emerging cell-based medicine., SPhERe Proceedings: 4th International Symposium on Pharmaceutical Engineering Research

Dermatoses are skin diseases caused by lowered level of lipids in the intercellular lipid matrix of skin’s uppermost layer stratum corneum. A promising therapy is the application of liposomally formulated skin lipids (ceramides, cholesterol, fatty acids). These so called cerosomes proved very effective in disrupted skin barrier repair; however, they aim primarily on a mechanical surface restoration. For this reason an interesting idea is to combine the cerosomes and anti-inflammatory drugs (such as hydrocortisone) used for the treatment of pathophysiological processes in the skin. Unfortunately, liposomes generally show low drug encapsulation rates, hence they would not be very effective carriers. On the other hand, great encapsulation effectivity can be found in lipid nanocapsules (LNCs). We therefore aimed to create a combined system cerosomes-LNCs that would ensure the skin barrier restoration thanks to the ceramides and simultaneously effectively deliver hydrocortisone as a representative of anti-inflammatory drugs into lower layers of the skin. In this work, we characterized the formulations by dynamic light scattering and transmission electron microscopy to assess their size and morphology., SPhERe Proceedings: 4th International Symposium on Pharmaceutical Engineering Research

In this study, a novel approach was developed for determining the density of compacts using ultraviolet–visible spectrophotometry. The assumption within this context was that a change in density affects the corresponding color information of the compact. From the obtained spectra of the visible range, the color information of the compact was calculated which turned out to be directly proportional to the density of the compact. In comparison, the obtained spectra were analyzed using partial least square regression. The results of this study showed that both methods could be used predicting the density of a compact from the corresponding visible spectrum at identical accuracy. In contrast to the partial least square regression, the correlation of the color information as a direct output parameter of the spectrophotometer with the density required no excessive data pre-processing. Subsequently, the easier and faster data processing of the color information over the partial least square regression, conceives using this novel approach as potential process analytical technology tool for implementation into a compression process e.g., tableting or roller compaction., SPhERe Proceedings: 4th International Symposium on Pharmaceutical Engineering Research

In situ tissue engineering requires to functionalize the surfaces of implants, to achieve better biocompatibility or to release pharmaceuticals. Often a burst release of such pharmaceuticals takes place and the surface functionality is gone rapidly. Casein-micelles (M-Cas) offer unique release capabilities for hydrophobic and hydrophilic substances. In this work, M-Cas were reconstructed and used as release system for curcumin as a model drug. Modified electrospun polycaprolactone (PCL)-fiber mats were coated with chitosan / tripolyphosphate nanoparticles (CS/TPP-NP) and functionalized with the reconstructed M-Cas. [1] CS/TPP-NPs and Na-caseinate (Cas) were used as blocking layer to slow down the release of curcumin loaded micelles. The layers were investigated by surface zeta-potential (ZP). The release of the curcumin from surfaces was possible and the blocking layers had a significant influence on the kinetics., SPhERe Proceedings: 4th International Symposium on Pharmaceutical Engineering Research

Solid triglyceride nanoparticles are under intensive investigation as drug delivery systems. In the solid state, triglycerides exist in three polymorphic modifications which differ from each other in their physicochemical properties. Thus, it is particularly important to know the influence of parameters affecting the polymorphic behavior of the solid triglyceride nanoparticles to get a stable product with defined physicochemical properties over an appropriate storage time. This study investigated the effect of subsequent addition of SDS to tripalmitin nanoparticles, which had been stabilized with partially hydrolyzed poly(vinyl alcohol) (PVA). The polymorphic behavior was characterized with DSC and X-ray diffraction over a storage time of 28 d at 20 °C. A faster transition into more stable polymorphic modifications was observed after the addition of SDS to the nanoparticles., SPhERe Proceedings: 4th International Symposium on Pharmaceutical Engineering Research

Novel Polymerized Ionic Liquids (PILs)-based Hydrogels as Innovative Drug Delivery Systems are presented. The embedding of drugs in hydrogels enables the “smart” delivery of bioactive molecules from drugs for an oral route of administration. Therefore, a high mechanical strength as well as a favorable pH-dependent swelling behavior is required which is shown in this study. A mechanical compression of PILs-based hydrogels up to 98.5% and a high swelling behavior of poly(VEImBr) hydrogels in a solution with a high pH value is achieved. A significant lower swelling is achieved in a solution with a lower pH value., SPhERe Proceedings: 3rd International Symposium on Pharmaceutical Engineering Research

Polycyclic polyprenylated acylphloroglucinols (PPAPs) exhibit a broad range of biological activities, such as antidepressant, antibacterial, antiviral and antitumor properties. The content of PPAPs in the producing plants is often quite low, and their complex structures make total chemical synthesis difficult and economically impractical. Progresses in synthetic biology provide an alternative approach for the production of these valuable compounds. Here we present our results on reconstruction of the biosynthetic pathways of PPAP precursors in yeast. Based on our previous works on the biosynthesis of PPAPs, genes involved in the formation of benzophenones and xanthones from Hypericum sp. and other organisms were expressed in yeast either episomally or by integration into the genome. The production of the expected products reached around 0.5 mg/l, which is high enough to be the substrate for enzymes of subsequent biosynthetic steps. The yeast strains will be further engineered by introducing various prenyltransferase enzymes to reconstruct the full biosynthetic pathways of PPAPs., SPhERe Proceedings: 3rd International Symposium on Pharmaceutical Engineering Research

A sufficient mechanical stability of tablets to be compacted prevents problems during tableting (e.g. sticking, capping, lamination) and is crucial with regard to further processing steps such as coating or packaging. Often, an improvement of the mechanical stability is only achievable by an adaption of the production settings (die disk speed) or an alteration of the powder blend composition. In the present study, a novel lower punch vibration device was developed and implemented on a rotary tablet press to improve the mechanical stability of the resulting tablets without changing the production conditions or the powder formulation. Various types of microcrystalline cellulose with different physical properties were selected. The powders were investigated concerning their powder flow, density, particle morphology and surface area and the tablets concerning their weight, tensile strength, and capping index. The results showed that externally applied lower punch vibration improved the mechanical stability of the investigated tablets beyond the adaption of the production settingss and the physical properties of the powder blend., SPhERe Proceedings: 3rd International Symposium on Pharmaceutical Engineering Research

The successful transfer from batch to a continuous flow process in a fixed bed reactor of a ligand in metalorganic API synthesis, the diazolium salt 1,3-methyl-benzoimidazol-3-ium iodide, is presented. Results show similar yields and conversion rates at corresponding process parameters in batch and continuous mode. By exceeding temperature limitation of a non-pressurized batch process, the pressurized continuous reactor system shows the potential for outperforming the batch synthesis regarding space time yield. Hence, process intensification by continuous flow presents itself as a viable approach for the heterogeneous di-N-alkylation of diazoles. Alternative basic reagents and solvents further enhance the viability of a continuous approach by addressing limitations such as side reactions and solubility of the reagent., SPhERe Proceedings: 3rd International Symposium on Pharmaceutical Engineering Research

SPhERe Proceedings: 3rd International Symposium on Pharmaceutical Engineering Research

A high pressure and high temperature continuous flow reactor has been used to intensify a Krapcho dealkoxycarbonylation reaction in the context of API synthesis. The reactor enables operation of the reaction above temperatures possible in batch and thus significantly increased conversion rates are achieved. Also a broader choice of solvents is possible by the use of the continuous process. Batch and continuous reaction are compared in terms of operation range and space-time-yield. Despite lower concentrations of the reactants in the continuous process, space-time-yield exceeds that of the batch process by more than an order of magnitude due to the higher reaction rates., SPhERe Proceedings: 3rd International Symposium on Pharmaceutical Engineering Research

Gold organometallic compounds have been extensively investigated as potential anticancer metallodrugs and have shown a high potential regarding antiproliferative effects [Hickey, 2008; Andermark, 2016; Meyer, 2012; Schmidt, 2019]. Enhanced stability is a driving argument for the design of gold complexes with N-heterocyclic carbene (NHC) ligands. The more surprising is the lack of methods of pharmaceutical analytics for their stability and solution chemistry. Such analytical methods are important key elements for future metabolomic investigations and will help to ensure a better understanding of the biological behavior of the complexes [Kostiainen, 2003]. We selected complexes of the type of alkynylgold(I)(NHC) for detailed stability studies by HPLC-DAD-MS, in comparison to the well-known antirheumatic drug Auranofin. A RP-based chromatographic method was established to separate possible degradation products of alkynylgold(I)(NHC) complexes. The stability studies were performed at 37°C over 24h using dimethylformamide (DMF), dimethyl sulfoxide (DMSO), water and Dulbecco`s modified eagle medium (DMEM) solutions of each compound. Furthermore, interaction experiments of alkynylgold(I)(NHC) complexes with acetylcysteine are under way with the same set-up as the stability tests [Albert 2012]. ESI (+) and (-) ionisation with a quadrupole analyser was used for mass spectrometry. The first results indicate that alkynylgold(I)(NHC) complexes are stable in the analysed solvents with no significant changes in their AUCs [Fig 2]., SPhERe Proceedings: 3rd International Symposium on Pharmaceutical Engineering Research

The model of the cultured single cell is considered insufficient to explain the physiological regulation taking place at the organ level. The same is true for the prediction of drug action at the organ level or at the level of the intact organism. For these reasons 3D cell culture models are in increasing demand. It is thus necessary to develop the instruments to handle such cell aggregates and organoids in a controlled, precise and gentle manner. Here, a microgripper is presented which is able to work in aqueous solutions and which is compatible with electrophysiological recordings of the cells immobilized by it. It was successfully employed to position isolated pancreatic islets and a 3D cell culture model of insulin-secreting cells, the so-called MIN6-pseudoislet. As required it was possible to measure the membrane potential of cells within these aggregates without any interference from the microgripper., SPhERe Proceedings: 3rd International Symposium on Pharmaceutical Engineering Research

The rapid development of affordable medications relies on the knowledge of suitable solvents for potential active pharmaceutical ingredients. Molecular simulations can be interpreted as computational experiments and may complement laboratory experiments, as they not only enable the calculation of thermophysical properties but also allow for an insight into a systems behavior on the molecular level. Relative solubilities can be predicted by using molecular simulations to calculate the Gibbs free energy of solvation ΔGsolv. We developed algorithms to reduce the required computational effort and increase the statistical precision by improved alchemical pathways. However, the agreement between ΔGsolv predictions from simulations and experimental data depends on the molecular models (force fields) used. To consider polarization effects, we combined partial charges derived by the IPolQ-Mod method with the General Amber Force Field (GAFF) and found a comparable ΔGsolv accuracy to GAFF and its default RESP charges for a large set of compounds in various solvents. We initiated a parameter optimization to improve the accuracy of GAFF/IPolQ-Mod and present our current results of the refitting process., SPhERe Proceedings: 3rd International Symposium on Pharmaceutical Engineering Research

Colloidal dispersions of lipids, e.g. triglycerides, are under intensive investigation as drug delivery systems. Solid triglyceride nanoparticles exist in different polymorphic modifications. The aim of this study was to investigate the effects of the addition of glycerol, which can be used for the isotonization of such dispersions, on the polymorphic behavior of poly(vinyl alcohol)-stabilized tripalmitin nanoparticles. Glycerol was added to the nanoparticle dispersions at different concentrations in the heat. The dispersions were investigated for their thermal behavior and storage stability with regard to particle size and polymorphic transitions of the triglyceride matrix, using photon correlation spectroscopy, differential scanning calorimetry and X-ray diffraction. The addition of glycerol led to a decreasing crystallization temperature of the nanoparticles and slowed down the polymorphic transition into the stable β-modification., SPhERe Proceedings: 3rd International Symposium on Pharmaceutical Engineering Research

A process yielding water stable chitosan nanofiber mats is described and their significance in the field of biocatalyst immobilization is proven. Electrospinning was adapted to produce nanofibers from chitosan derivatives bearing photoreactive arylazide groups. These photoreactive groups of chitosan were then crosslinked by irradiation with UV-light. This stabilizes the fiber morphology even upon incubation in water and provides an alternative to crosslinking with harmful chemicals. Applicability of the fiber mats as enzyme immobilization matrix was demonstrated, using β-D-galactosidase as model enzyme. Although an initial leaching of enzyme was observed, after 40 days of incubation a significant portion of active enzyme is still present on the fibers. Thus, the fiber mats are suitable matrices to support enzymes and can revolutionize future enzymatic production processes of e.g. active pharmaceutical ingredients., SPhERe Proceedings: 3rd International Symposium on Pharmaceutical Engineering Research

The delivery of poorly water-soluble bioactives, including active pharmaceutical ingredients (API) and nutraceutical components is of great interest for existing drugs and new drug developments, cosmetic formulations, functional foods and nutraceuticals. This article presents a novel patented technology called PGX Technology, which utilizes pressurized gas expanded (PGX) liquids to dry, micronize, purify and functionalize water-soluble polymers. PGX Technology can generate open-porous nanostructured polymer carriers composed of one or several water-soluble polymers forming powders, granules, nano-fibrils, aerogels and exfoliated nano-composites with specific surface areas (SSA) ranging from tens to several hundred m2/g. Such mesoporous water-soluble carrier systems can be impregnated with a bioactive by means of adsorptive precipitation, utilizing supercritical carbon dioxide, leading to the uniform deposition of nano-scale particles (, SPhERe Proceedings: 3rd International Symposium on Pharmaceutical Engineering Research

The desired valuable ingredients determine the required solvent. After some thermodynamic consideration about supercritical fluids and the advantages of liquid and supercritical carbon dioxide for extraction purposes some exceptional examples for the recovery of active pharmaceutical ingredients of medicinal plants are discussed., SPhERe Proceedings: 3rd International Symposium on Pharmaceutical Engineering Research

The industrial implementation of whole-cells and enzymes in flow biocatalysis microreactors is essential for the emergence of a biobased circular economy. Major challenges concern the efficient immobilization of delicate enzymes inside miniaturized reactors without compromising their catalytic activity. We describe the design and application of four different immobilization techniques including self-immobilizing whole-cells and purified enzymes on magnetic microbeads, as well as reactor modules manufactured by 3D printing of bioinks containing thermostable enzymes. To increase the volumetric activity of our microreactors we furthermore developed and applied self-assembling all-enzyme hydrogels with cofactor-regenerating capabilities. The resulting reactor formats have excellent operational stability times of > 14 days and maximum space-time yields of > 450 g product/L-1day-1 paving the way for mild and effective immobilization techniques of biocatalysts in microfluidic systems., SPhERe Proceedings: 3rd International Symposium on Pharmaceutical Engineering Research

The dissolution of spray-dried amorphous solid dispersions consisting of paracetamol and PVP VA 64 at room temperature leads to the formation of different systems, depending on the drug/polymer ratio. Aqueous systems at room temperature with poor paracetamol/PVP VA 64 ratio are transparent solutions, while higher drug loads lead to phase separation of the solution. PVP VA 64 is known as thermoresponsive polymer. The aim of the study was to investigate the dissolution behaviour of these amorphous solid dispersions in water and their influence on the thermoresponsive behaviour of this polymer. Therefore, the demixing temperature was determined using DSC, since a change in the system constitutes an endothermic process. It could be shown that PVP VA 64 has lower critical solution temperature (LCST) behaviour around 70 °C, which decreases with increasing content of paracetamol due to the complex formation between the polymer and paracetamol., SPhERe Proceedings: 3rd International Symposium on Pharmaceutical Engineering Research

Parenteral nanoemulsions are regarded as biocompatible drug delivery systems for lypophilic drugs. When it comes to delivering actives to the brain as a target site, prolonged circulation time is desirable. The objective of this study was to conduct physicochemical characterization of PEGylated nanoemulsions as prospective carriers for enhanced brain delivery, using diazepam as a model active substance for brain targeting. Nanoemulsions were prepared by high pressure homogenization method and characterized regarding droplet size, zeta potential, pH, conductivity, viscosity and in vitro release profile. PEG2000-DSPE and PEG5000-DPPE were used for PEGylation. All the formulations were autoclaved and stored at room temperature. After 2 months there were no significant changes in physicochemical parameters in autoclaved formulations which rendered them as good potential templates to incorporate drugs for brain targeted delivery., SPhERe Proceedings: 3rd International Symposium on Pharmaceutical Engineering Research

Ion-exchange chromatography (IEC) is the most frequently used technique to purify proteins and therefore, plays an important role in process development for therapeutical proteins. To improve the purification using ion-exchange chromatography, adequate characterization of adsorption isotherms is obligatory. The Elution by Characteristic Point method (ECP) can be used to determine adsorption isotherms applying only minor amounts of sample material to the chromatography column. Here, the applicability of the extended ECP method to determine adsorption isotherms of the model protein bovine serum albumin (BSA) using bovine hemoglobin (bHb) as tracer substance to quantify all nonidealities of the system is shown. The resulting isotherm was validated using the static batch approach. In the next step, the gained knowledge is used to measure isotherms of Labyrinthopeptins A1 and A2, which show promising activity against retroviruses like herpes simplex virus or human immunodeficiency virus., SPhERe Proceedings: 3rd International Symposium on Pharmaceutical Engineering Research

Considering the numerous organizational and legislative issues associated with in vivo studies, the present study aimed to develop in vitro tape stripping protocol that could serve as a prospective technique for skin penetration studies. The research was mainly focused on the suitability of transepidermal water loss (TEWL) measurements, as a barrier integrity test for porcine ear skin subjected to freezing/thawing procedure, as well as on the selection of the most suitable device for pressing adhesive tapes onto the porcine ear surface during skin stripping procedure. Obtained results suggest that TEWL measurements were able to detect the damage of the stratum corneum (SC) caused by physical impairment (using adhesive tapes) and tissue degradation/dehydration (prolonged storage at –20ºC/ambient conditions). Penetration profiles of aceclofenac from nanoemulsions based on sucrose esters or polysorbate 80 as coemulsifiers, obtained in vitro (using a roller as pressure device), were in a good agreement with data obtained in vivo on humans, supporting the use of developed in vitro tape-stripping protocol in skin formulation development and optimization., SPhERe Proceedings: 3rd International Symposium on Pharmaceutical Engineering Research

Premix membrane emulsification is a promising method to produce colloidal lipid carrier systems, e.g. triglyceride nanoemulsions, with small particle sizes and narrow particle size distributions for intravenous administration. The stability of these systems can be affected by Ostwald ripening. The process of Ostwald ripening in emulsions of medium chain triglycerides stabilized with sucrose laurate was monitored by particle size measurements with photon correlation spectroscopy. Two different preparation methods were used and the concentration of free emulsifier measured to learn more about the influencing parameters. The concentration of free sucrose laurate turned out to be the main influencing parameter and should be about zero to minimize Ostwald ripening in the emulsions., SPhERe Proceedings: 3rd International Symposium on Pharmaceutical Engineering Research

Substances extracted from Cannabis varieties are of increasing interest, especially cannabidiol as a non-psychoactive drug with various pharmacological effects. Formulation of cannabidiol is, however, challenging due to its low water solubility. In this study, different types of lipid carriers were investigated as formulation options for cannabidiol to enable parenteral or oral application. The study included self-dispersing lipid formulations, nanoemulsions and liposomes. With regard to parenteral application, a higher load of cannabidiol was obtained in nanoemulsions than in liposomes. Lipid nanoemulsions are thus a very promising formulation option for parenteral formulations with a high drug load. Also in formulations intended for oral use a notably higher amount of cannabidiol could be incorporated in oil-containing self-dispersing formulations than in liposomes., SPhERe Proceedings: 3rd International Symposium on Pharmaceutical Engineering Research

Artemisinin-based combination therapies are recommended by the World Health Organization to treat malaria, one of the most abundant infectious diseases in the world. Recently, a novel production route, which combines the extraction and the catalyzed chemical synthesis, has been shown to be a promising sustainable processing alternative [Triemer, 2018]. To exploit its mechanism, operational settings and limits, mathematical modeling might be beneficial when thorough system insight is required. In a first step, we consider the catalyzed synthesis step from dihydroartemisinic acid to artemisinin, and we show that only a subset of the parameters of the considered model is identifiable with the available sparse data using a singular value decomposition approach. In a second step, within the framework of design of experiments (DoE), we demonstrate the effect of additional experimental data to overcome the non-identifiability problem of the model parameters., SPhERe Proceedings: 3rd International Symposium on Pharmaceutical Engineering Research

Filamentous microorganisms represent the majority of natural producers of antibiotics and other active pharmaceutical ingredients (APIs). Lentzea aerocolonigenes is a filamentous actinomycete producing the antitumor antibiotic rebeccamycin. The addition of glass beads (100 g/L, ⌀ = 969 μm) in shake flask cultivations led to a significant increase in rebeccamycin production compared to an unsupplemented cultivation by inducing mechanical stress. To achieve larger amounts of rebeccamycin a scale-up was conducted. A bubble free membrane aeration was chosen to reduce the power input to stirrer and particle induced stress. Glass bead addition (50 g/L, ⌀ = 969 μm) in this membrane aerated stirred bioreactor increased rebeccamycin concentration compared to an unsupplemented cultivation as well. Moreover it reduced biomass growth on the aeration membrane which is a widespread challenge in membrane aerated bioreactors., SPhERe Proceedings: 3rd International Symposium on Pharmaceutical Engineering Research

Solid dispersions have already been described over more than 50 years ago in scientific literature to improve solubility of poorly water soluble drugs. With the increasing number of new poorly soluble drug candidates discovered at early industrial stages, the knowledge about these metastable amorphous systems has significantly improved over the decades. While in the early days of solid dispersions pharmaceutical companies were rather very reluctant to invest in corresponding manufacturing technologies, nowadays a significant number of market drug products has been developed based upon this not novel drug delivery principle. The presentation will give an overview about properties of solid dispersions, industrial screening and manufacturing methods and the biopharmaceutical implications., SPhERe Proceedings: 3rd International Symposium on Pharmaceutical Engineering Research