Applying real life examples for improved learning outcomes

The aim of this project was to redesign and optimize a classroom lesson within the course “Drug Formulation” for BSc students in pharmacy by applying a ‘problem to solve’ teaching style in order to improve the students ability to apply and crosslink their knowledge about pharmaceutical formulations, i.e. support deeper learning and understanding rather than memory

Industrial processing of TiO2 thin films from soluble precursor powders

Soluble, amorphous powders were prepared as precursors for the sol-gel processing of TiO2 films. Layers of up to 800 nm and 2.0 μm were prepared on borosilicate glass and Ni-alloy by multiple coating, respectively. Α refractive index of 2.3 was achieved. The interdependency of parameters such as solvent composition, withdrawal rate, thermal treatment with film quality, thickness and optical properties was investigated. The conditions were optimized for large-area coatings on an industrial scale. The overall process is highly advantageous for industrial production of optical interference filters due to the long-time stability of precursor powders and sols, high optical quality of the resulting films, excellent substrate adhesion and good compatibility with other sol-gel films

Relationships between soil management and pathogen suppressive soils in southern Sweden

A holistic study on soil-borne pathogen management with suppressive soils was performed in Scania, Sweden. The study was designed to comprise both social and biological research to gain a systemic perspective on the real-life situation of Swedish farmers regarding plant pathogens and soil management. The social research comprised semi-structured interviews with a small number of farmers and an online survey, which could not be sent to farmers and therefore was without results. Possible reasons for the failure are discussed. For the biological research, soils from ten Swedish farms with different cropping and management regimes were assessed for effects on Pythium ultimum disease symptoms in wheat, physical and chemical soil parameters, and the soil nematode trophic community as identified at the family level. Soil effects on Pythium ultimum disease symptoms were assessed in two categories: (1) biological or non-biological effects and (2) suppressive or conducive effects. Different soils had both conducive and suppressive effects, which were due to either the soil biotic community or chemical or physical properties of the soil. Management regimes with permanent plant cover had biological effects and management regimes with interrupted plant cover had non-biological effects. The nutrient balance was related to biological suppressiveness. Biologically conducive soils had either high or low nutrient content, while biologically suppressive soils had intermediate nutrient levels. The total number of nematodes and the abundance of predators and omnivores were not related to the soil organic matter content. The abundance of hyphal-feeding nematodes was correlated with soil organic matter content. No relationship was found between the soil nematode trophic community, the soil management, and soil effects on Pythium ultimum disease symptoms. Therefore, nematode trophic guilds do not indicate soil effects on Pythium ultimum disease symptoms

Influence of Solvent Composition on the Performance of Spray-Dried Co-Amorphous Formulations

Ball-milling is usually used to prepare co-amorphous drug–amino acid (AA) mixtures. In this study, co-amorphous drug–AA mixtures were produced using spray-drying, a scalable industrially preferred preparation method. The influence of the solvent type and solvent composition was investigated. Mixtures of indomethacin (IND) and each of the three AAs arginine, histidine, and lysine were ball-milled and spray-dried at a 1:1 molar ratio, respectively. Spray-drying was performed at different solvent ratios in (a) ethanol and water mixtures and (b) acetone and water mixtures. Different ratios of these solvents were chosen to study the effect of solvent mixtures on co-amorphous formulation. Residual crystallinity, thermal properties, salt/partial salt formation, and powder dissolution profiles of the IND–AA mixtures were investigated and compared to pure crystalline and amorphous IND. It was found that using spray-drying as a preparation method, all IND–AA mixtures could be successfully converted into the respective co-amorphous forms, irrespective of the type of solvent used, but depending on the solvent mixture ratios. Both ball-milled and spray-dried co-amorphous samples showed an enhanced dissolution rate and maintained supersaturation compared to the crystalline and amorphous IND itself. The spray-dried samples resulting in co-amorphous samples were stable for at least seven months of storage

Predicting Crystallization of Amorphous Drugs with Terahertz Spectroscopy.

There is a controversy about the extent to which the primary and secondary dielectric relaxations influence the crystallization of amorphous organic compounds below the glass transition temperature. Recent studies also point to the importance of fast molecular dynamics on picosecond-to-nanosecond time scales with respect to the glass stability. In the present study we provide terahertz spectroscopy evidence on the crystallization of amorphous naproxen well below its glass transition temperature and confirm the direct role of Johari-Goldstein (JG) secondary relaxation as a facilitator of the crystallization. We determine the onset temperature Tβ above which the JG relaxation contributes to the fast molecular dynamics and analytically quantify the level of this contribution. We then show there is a strong correlation between the increase in the fast molecular dynamics and onset of crystallization in several chosen amorphous drugs. We believe that this technique has immediate applications to quantify the stability of amorphous drug materials.JS and JAZ would like to acknowledge the UK Engineering and Physical Sciences Research Council for funding (EP/J007803/1).This is the final version of the article. It first appeared from ACS at http://dx.doi.org/10.1021/acs.molpharmaceut.5b0033

Sustainable soil management measures: a synthesis of stakeholder recommendations

Soil degradation threatens agricultural production and soil multifunctionality. Efforts for private and public governance are increasingly emerging to leverage sustainable soil management. They require consensus across science, policy, and practice about what sustainable soil management entails. Such agreement does not yet exist to a sufficient extent in agronomic terms; what is lacking is a concise list of soil management measures that enjoy broad support among all stakeholders, and evidence on the question what hampers their implementation by farmers. We therefore screened stakeholder documents from public governance institutions, nongovernmental organizations, the agricultural industry, and conventional and organic farmer associations for recommendations related to agricultural soil management in Germany. Out of 46 recommended measures in total, we compiled a shortlist of the seven most consensual ones: (1) structural landscape elements, (2) organic fertilization, (3) diversified crop rotation, (4) permanent soil cover, (5) conservation tillage, (6) reduced soil loads, and (7) optimized timing of wheeling. Together, these measures support all agricultural soil functions, and address all major soil threats except soil contamination. Implementation barriers were identified with the aid of an online survey among farmers (n = 78). Results showed that a vast majority of farmers (> 80%) approved of all measures. Barriers were mostly considered to be economic and in some cases technological, while missing knowledge or other factors were less relevant. Barriers were stronger for those measures that cannot be implemented in isolation, but require a systemic diversification of the production system. This is especially the case for measures that are simultaneously beneficial to many soil functions (measures 2, 3, and 4). Results confirm the need for a diversification of the agricultural system in order to meet challenges of food security and climate change. The shortlist presents the first integrative compilation of sustainable soil management measures supporting the design of effective public or private governance

Examination of efficacy and selectivity of herbicides in ALS-tolerant sugar beets

The development of herbicide-tolerant sugar beet varieties offers the possibility to use only herbicides from the group of the aceto-lactate synthase (ALS) inhibitors. At present, ALS inhibitors are used in many crops of the rotation to a significant extent, in particular in cereals and maize. However, more than 159 weed species with resistance to ALS inhibitors are known. Consequently, this is the mode of action with most cases of herbicide resistances. The advancing spread of ALS-resistant weeds is a major challenge for herbicide management, if herbicide ALS-tolerant crops are used. The present study was concerned with the question of which herbicide strategies ensure the efficacy of the new herbicide CONVISO® with and without presence of ALS-resistant weeds. Furthermore, the selectivity in ALS-tolerant sugar beet was investigated. Without presence of ALS-resistant weeds one treatment with CONVISO® was sufficient for weed control. With a splitting application and use of an additive the CONVISO® efficacy could be improved. The application of CONVISO® herbicide caused no visual symptoms or yield loss in the sugar beet. ALS-resistant weeds were only partly controlled by CONVISO® herbicide. By using tank mixtures with other modes of action efficacy could be improved, but complete control of ALS-resistant weeds was not possible

Process Optimization and Upscaling of Spray-Dried Drug-Amino acid Co-Amorphous Formulations

The feasibility of upscaling the formulation of co-amorphous indomethacin-lysine from lab-scale to pilot-scale spray drying was investigated. A 22 full factorial design of experiments (DoE) was employed at lab scale. The atomization gas flow rate (Fatom, from 0.5 to 1.4 kg/h) and outlet temperature (Tout, from 55 to 75 °C) were chosen as the critical process parameters. The obtained amorphization, glass transition temperature, bulk density, yield, and particle size distribution were chosen as the critical quality attributes. In general, the model showed low Fatom and high Tout to be beneficial for the desired product characteristics (a co-amorphous formulation with a low bulk density, high yield, and small particle size). In addition, only a low Fatom and high Tout led to the desired complete co-amorphization, while a minor residual crystallinity was observed with the other combinations of Fatom and Tout. Finally, upscaling to a pilot scale spray dryer was carried out based on the DoE results; however, the drying gas flow rate and the feed flow rate were adjusted to account for the different drying chamber geometries. An increased likelihood to achieve complete amorphization, because of the extended drying chamber, and hence an increased residence time of the droplets in the drying gas, was found in the pilot scale, confirming the feasibility of upscaling spray drying as a production technique for co-amorphous systems

The Influence of Polymers on the Supersaturation Potential of Poor and Good Glass Formers

The increasing number of poorly water-soluble drug candidates in pharmaceutical development is a major challenge. Enabling techniques such as amorphization of the crystalline drug can result in supersaturation with respect to the thermodynamically most stable form of the drug, thereby possibly increasing its bioavailability after oral administration. The ease with which such crystalline drugs can be amorphized is known as their glass forming ability (GFA) and is commonly described by the critical cooling rate. In this study, the supersaturation potential, i.e., the maximum apparent degree of supersaturation, of poor and good glass formers is investigated in the absence or presence of either hypromellose acetate succinate L-grade (HPMCAS-L) or vinylpyrrolidine-vinyl acetate copolymer (PVPVA64) in fasted state simulated intestinal fluid (FaSSIF). The GFA of cinnarizine, itraconazole, ketoconazole, naproxen, phenytoin, and probenecid was determined by melt quenching the crystalline drugs to determine their respective critical cooling rate. The inherent supersaturation potential of the drugs in FaSSIF was determined by a solvent shift method where the respective drugs were dissolved in dimethyl sulfoxide and then added to FaSSIF. This study showed that the poor glass formers naproxen, phenytoin, and probenecid could not supersaturate on their own, however for some drug:polymer combinations of naproxen and phenytoin, supersaturation of the drug was enabled by the polymer. In contrast, all of the good glass formers—cinnarizine, itraconazole, and ketoconazole—could supersaturate on their own. Furthermore, the maximum achievable concentration of the good glass formers was unaffected by the presence of a polymer