Control of crystalline particle properties by spray drying

Although spray drying has been common place in the pharmaceutical industry for decades, the integration of the technique into continuous manufacturing can offer an extensive array of particle engineering applications. Continuous manufacturing aims to deliver consistent and sustainable drug products of a better and higher quality. Spray drying is a continuous processing technique typically adopted for amorphous solid production. However, the unique conditions of the technique can also can be adapted and applied to crystallisation enabling particle property engineering. The semi-continuous lab-scale Büchi B-290 Mini spray dryer is widely available and has been previously studied extensively for particle engineering and as a development platform for applications including pulmonary drug delivery, sustained release formulations and amorphous solid dispersions.The focus of this work is to engineer and enhance particle properties through the use of the Büchi spray dryer. Particle formation has been investigated, with specific focus in terms of polymorph formation in carbamazepine, to develop a predictive model for crystallisability and for co-spray drying of metformin hydrochloride with mannitol and lactose. Particle formation has been described in terms of theoretical drying kinetics and combined with off line characterisation to determine size and form of product. The metastable polymorph, form IV, of carbamazepine was made reproducibly by spray drying with the combination of rapid evaporation and product isolation shown to be crucial to prevention of solution mediated transformation. The application of non-invasive Raman spectroscopy was also utilised to assess product form. A crystallisability predictive model based on a Random Forest method was successfully produced through combining molecular descriptors with published and experimental outcomes. The model provided up to 79 % accuracy in predicting whether an amorphous or crystalline product would be expected from rapid drying. This shows considerable utility in streamlining process development. Finally, co-spray drying in the Büchi system using a three-fluid nozzle was used to produce multicomponent composite particles comprising of two crystallite phases. The effect of process configuration and material properties on the resultant particles was assessed using particle sizing, SEM, XRPD and Raman mapping. The results were compared on the basis of theoretical drying kinetics to assess the ability to predict the resultant particle morphology. Four multicomponent composite particles were produced by co-spray drying from metformin hydrochloride (MF), mannitol and lactose. MF-mannitol composites produced three-phase physical mixtures with both components present on the particle surfaces. The particle surface compositions were contradictory to the expected particle outcomes from the drying parameters. MF-lactose composite particle also produce three-phase physical mixtures with a relatively equal distribution of components present on particle surface. This is consistent with the expected particle from the drying parameters. The different particle outcomes suggest that co-spray drying of miscible multicomponent feeds using the three-fluid nozzle is highly dependent on the drying parameters for each component due to equal mixing of the feed at atomisation of droplets.Although spray drying has been common place in the pharmaceutical industry for decades, the integration of the technique into continuous manufacturing can offer an extensive array of particle engineering applications. Continuous manufacturing aims to deliver consistent and sustainable drug products of a better and higher quality. Spray drying is a continuous processing technique typically adopted for amorphous solid production. However, the unique conditions of the technique can also can be adapted and applied to crystallisation enabling particle property engineering. The semi-continuous lab-scale Büchi B-290 Mini spray dryer is widely available and has been previously studied extensively for particle engineering and as a development platform for applications including pulmonary drug delivery, sustained release formulations and amorphous solid dispersions.The focus of this work is to engineer and enhance particle properties through the use of the Büchi spray dryer. Particle formation has been investigated, with specific focus in terms of polymorph formation in carbamazepine, to develop a predictive model for crystallisability and for co-spray drying of metformin hydrochloride with mannitol and lactose. Particle formation has been described in terms of theoretical drying kinetics and combined with off line characterisation to determine size and form of product. The metastable polymorph, form IV, of carbamazepine was made reproducibly by spray drying with the combination of rapid evaporation and product isolation shown to be crucial to prevention of solution mediated transformation. The application of non-invasive Raman spectroscopy was also utilised to assess product form. A crystallisability predictive model based on a Random Forest method was successfully produced through combining molecular descriptors with published and experimental outcomes. The model provided up to 79 % accuracy in predicting whether an amorphous or crystalline product would be expected from rapid drying. This shows considerable utility in streamlining process development. Finally, co-spray drying in the Büchi system using a three-fluid nozzle was used to produce multicomponent composite particles comprising of two crystallite phases. The effect of process configuration and material properties on the resultant particles was assessed using particle sizing, SEM, XRPD and Raman mapping. The results were compared on the basis of theoretical drying kinetics to assess the ability to predict the resultant particle morphology. Four multicomponent composite particles were produced by co-spray drying from metformin hydrochloride (MF), mannitol and lactose. MF-mannitol composites produced three-phase physical mixtures with both components present on the particle surfaces. The particle surface compositions were contradictory to the expected particle outcomes from the drying parameters. MF-lactose composite particle also produce three-phase physical mixtures with a relatively equal distribution of components present on particle surface. This is consistent with the expected particle from the drying parameters. The different particle outcomes suggest that co-spray drying of miscible multicomponent feeds using the three-fluid nozzle is highly dependent on the drying parameters for each component due to equal mixing of the feed at atomisation of droplets

Adaptive evolution of synchronous egg-hatching in compensation for the loss of parental care.

Interactions among siblings are finely balanced between rivalry and cooperation, but the factors that tip the balance towards cooperation are incompletely understood. Previous observations of insect species suggest that (i) sibling cooperation is more likely when siblings hatch at the same time, and (ii) this is more common when parents provide little to no care. In this paper, we tested these ideas experimentally with the burying beetle, Nicrophorus vespilloides Burying beetles convert the body of a small dead vertebrate into an edible nest for their larvae, and provision and guard their young after hatching. In our first experiment, we simulated synchronous or asynchronous hatching by adding larvae at different intervals to the carrion-breeding resource. We found that 'synchronously' hatched broods survived better than 'asynchronously' hatched broods, probably because 'synchronous hatching' generated larger teams of larvae, that together worked more effectively to penetrate the carrion nest and feed upon it. In our second experiment, we measured the synchronicity of hatching in experimental populations that had evolved for 22 generations without any post-hatching care, and control populations that had evolved in parallel with post-hatching care. We found that larvae were more likely to hatch earlier, and at the same time as their broodmates, in the experimental populations that evolved without post-hatching care. We suggest that synchronous hatching enables offspring to help each other when parents are not present to provide care. However, we also suggest that greater levels of cooperation among siblings cannot compensate fully for the loss of parental care

Spray drying as a reliable route to produce metastable carbamazepine form IV

Carbamazepine is an active pharmaceutical ingredient used in the treatment of epilepsy that can form at least five polymorphic forms. Metastable form IV was originally discovered from crystallisation with polymer additives however has not been observed from subsequent solvent only crystallisation efforts. This work reports the reproducible formation of phase pure crystalline form IV by spray drying of methanolic carbamazepine solution. Characterisation of the material was carried out using diffraction, SEM and DSC. In situ Raman spectroscopy was used to monitor the spray dried product during the spray drying process. This work demonstrates spray drying provides a robust method for the production of form IV carbamazepine and the combination of high supersaturation and rapid solid isolation from solution overcomes the apparent limitation of more traditional solution crystallisation approaches to produce metastable crystalline forms

Effectiveness of a brief school-based body image intervention 'Dove Confident Me: Single Session' when delivered by teachers and researchers: Results from a cluster randomised controlled trial

a b s t r a c t This study evaluated a 90-min single session school-based body image intervention (Dove Confident Me: Single Session), and investigated if delivery could be task-shifted to teachers. British adolescents (N ¼ 1707; 11e13 years; 50.83% girls) participated in a cluster randomised controlled trial [lessons as usual control; intervention teacher-led (TL); intervention researcher-led (RL)]. Body image, risk factors, and psychosocial and disordered eating outcomes were assessed 1-week pre-intervention, immediate post-intervention, and 4e9.5 weeks follow-up. Multilevel mixed-models showed post-intervention improvements for intervention students relative to control in body esteem (TL; girls only), negative affect (TL), dietary restraint (TL; girls only), eating disorder symptoms (TL), and life engagement (TL; RL). Awareness of sociocultural pressures increased at post-intervention (TL). Effects were small-medium in size (ds 0.19e0.76) and were not maintained at follow-up. There were no significant differences between conditions at post or follow-up on body satisfaction, appearance comparisons, teasing, appearance conversations and self-esteem. The intervention had short-term benefits for girls' body image and dietary restraint, and for eating disorder symptoms and some psychosocial outcomes among girls and boys. A multi-session version of the intervention is likely to be necessary for sustained improvements. Teachers can deliver this intervention effectively with minimal training, indicating broader scale dissemination is feasible. Trial registration: ISRCTN16782819

Effectiveness of a brief school-based body image intervention 'Dove Confident Me: Single Session' when delivered by teachers and researchers: Results from a cluster randomised controlled trial

© 2015 The Authors. This study evaluated a 90-min single session school-based body image intervention (Dove Confident Me: Single Session), and investigated if delivery could be task-shifted to teachers. British adolescents (N = 1707; 11-13 years; 50.83% girls) participated in a cluster randomised controlled trial [lessons as usual control; intervention teacher-led (TL); intervention researcher-led (RL)]. Body image, risk factors, and psychosocial and disordered eating outcomes were assessed 1-week pre-intervention, immediate post-intervention, and 4-9.5 weeks follow-up. Multilevel mixed-models showed post-intervention improvements for intervention students relative to control in body esteem (TL; girls only), negative affect (TL), dietary restraint (TL; girls only), eating disorder symptoms (TL), and life engagement (TL; RL). Awareness of sociocultural pressures increased at post-intervention (TL). Effects were small-medium in size (ds 0.19-0.76) and were not maintained at follow-up. There were no significant differences between conditions at post or follow-up on body satisfaction, appearance comparisons, teasing, appearance conversations and self-esteem. The intervention had short-term benefits for girls' body image and dietary restraint, and for eating disorder symptoms and some psychosocial outcomes among girls and boys. A multi-session version of the intervention is likely to be necessary for sustained improvements. Teachers can deliver this intervention effectively with minimal training, indicating broader scale dissemination is feasible. Trial registration: ISRCTN16782819

Disability rights and robotics: Co-producing futures

This project brought together a team of 25 co-researchers from the University of the West of England, Fairfield Farm College and Wiltshire Centre of Independent Living. The co-researchers are a diverse group including disabled people, carers, students, and academics from social work, psychology and sociology to robotics. Our research team demonstrates a wealth of experiences as some members had both lived experience of disability, in addition to being involved in teaching, learning and research. The research question for the project was:How can robotic technologies support disability rights? Rights are about everyday opportunities to live life to the full, human rights that everyone is entitled to (The Convention on the Rights of Persons with Disabilities (CRPD) 2009 (Enable.un.org, 2019). In this time of rapid social change to our social and work lives, relationships and leisure, there are new technologies that might support disability rights like ‘driverless cars’, smart phones, social media and new robotic technologies. The project had two aims:•to identify priority research questions into disability rights and robotics•to develop the co-production process for future researc

Autonomous and Lagrangian ocean observations for Atlantic tropical cyclone studies and forecasts

Author Posting. © The Oceanography Society, 2017. This article is posted here by permission of The Oceanography Society for personal use, not for redistribution. The definitive version was published in Oceanography 30, no. 2 (2017): 92–103, doi:10.5670/oceanog.2017.227.The tropical Atlantic basin is one of seven global regions where tropical cyclones (TCs) commonly originate, intensify, and affect highly populated coastal areas. Under appropriate atmospheric conditions, TC intensification can be linked to upper-ocean properties. Errors in Atlantic TC intensification forecasts have not been significantly reduced during the last 25 years. The combined use of in situ and satellite observations, particularly of temperature and salinity ahead of TCs, has the potential to improve the representation of the ocean, more accurately initialize hurricane intensity forecast models, and identify areas where TCs may intensify. However, a sustained in situ ocean observing system in the tropical North Atlantic Ocean and Caribbean Sea dedicated to measuring subsurface temperature, salinity, and density fields in support of TC intensity studies and forecasts has yet to be designed and implemented. Autonomous and Lagrangian platforms and sensors offer cost-effective opportunities to accomplish this objective. Here, we highlight recent efforts to use autonomous platforms and sensors, including surface drifters, profiling floats, underwater gliders, and dropsondes, to better understand air-sea processes during high-wind events, particularly those geared toward improving hurricane intensity forecasts. Real-time data availability is key for assimilation into numerical weather forecast models.The NOAA/AOML component of this work was originally funded by the Disaster Relief Appropriations Act of 2013, also known as the Sandy Supplemental, and is currently funded through NOAA research grant NA14OAR4830103 by AOML and CARICOOS, as well as NOAA’s Integrated Ocean Observing System (IOOS). The TEMPESTS component of this work is supported by NOAA through the Cooperative Institute for the North Atlantic Region (NA13OAR4830233) with additional analysis support from the WHOI Summer Student Fellowship Program, Nortek Student Equipment Grant, and the Rutgers University Teledyne Webb Graduate Student Fellowship Program. The drifter component of this work is funded through NOAA grant NA15OAR4320071(11.432) in support of the Global Drifter Program

Internalization as a mediator of the relationship between conformity to masculine norms and body image attitudes and behaviors among young men in Sweden, US, UK, and Australia

© 2015 Elsevier Ltd. We examined whether internalization of sociocultural body ideals mediated the relationship between conformity to masculine norms and drive for muscularity, leanness, and thinness in a sample of males from Sweden, US, UK, and Australia. Over six hundred young men [n= 142 (Sweden); n= 192 (US); n= 141 (UK); n= 160 (Australia)] completed an online survey that included assessments of masculine role norms, body image, and internalization of sociocultural body ideals. Path analyses confirmed internalization as a mediator between greater conformity to masculine norms and body image measures (drive for thinness, desire for leanness, and desire for muscularity) across the sample. However, significant cross-country differences in the strength of these mediation effects were found. Mediation effects among US, Australian, and Swedish males were comparable, whereas these effects were weaker in the UK sample. Findings confirmed the importance of internalization of sociocultural body ideals in the tested models

The oxidation of dehydroascorbic acid and 2,3-diketogulonate by distinct reactive oxygen species

l-Ascorbate, dehydro-l-ascorbic acid (DHA), and 2,3-diketo-l-gulonate (DKG) can all quench reactive oxygen species (ROS) in plants and animals. The vitamin C oxidation products thereby formed are investigated here. DHA and DKG were incubated aerobically at pH 4.7 with peroxide (H2O2), 'superoxide' (a ∼50 : 50 mixture of [Formula: see text] and [Formula: see text]), hydroxyl radicals (•OH, formed in Fenton mixtures), and illuminated riboflavin (generating singlet oxygen, 1O2). Products were monitored electrophoretically. DHA quenched H2O2 far more effectively than superoxide, but the main products in both cases were 4-O-oxalyl-l-threonate (4-OxT) and smaller amounts of 3-OxT and OxA + threonate. H2O2, but not superoxide, also yielded cyclic-OxT. Dilute Fenton mixture almost completely oxidised a 50-fold excess of DHA, indicating that it generated oxidant(s) greatly exceeding the theoretical •OH yield; it yielded oxalate, threonate, and OxT. 1O2 had no effect on DHA. DKG was oxidatively decarboxylated by H2O2, Fenton mixture, and 1O2, forming a newly characterised product, 2-oxo-l-threo-pentonate (OTP; '2-keto-l-xylonate'). Superoxide yielded negligible OTP. Prolonged H2O2 treatment oxidatively decarboxylated OTP to threonate. Oxidation of DKG by H2O2, Fenton mixture, or 1O2 also gave traces of 4-OxT but no detectable 3-OxT or cyclic-OxT. In conclusion, DHA and DKG yield different oxidation products when attacked by different ROS. DHA is more readily oxidised by H2O2 and superoxide; DKG more readily by 1O2 The diverse products are potential signals, enabling organisms to respond appropriately to diverse stresses. Also, the reaction-product 'fingerprints' are analytically useful, indicating which ROS are acting in vivo