68 research outputs found
Predicting the Risk of Crystallization for Suspensions of Amorphous Spray Dried Dispersions from Structural, Thermal and Hydrophilicity Properties
No full textSuspensions of spray dried amorphous dispersions are a valuable tool for enhancing the exposure of poorly soluble compounds in preclinical animal models. However, limitations in drug supply and time/cost of manufacture in the drug discovery space make it desirable to predict the likelihood of obtaining a physically stable (free from detectable crystallization) suspension prior to synthetic scale-up and processing of a candidate compound. Background information on this topic is covered in Chapter 1. For 33.3% drug load solid dispersions in Hydroxypropylmethyl cellulose acetate succinate (HPMCAS) suspended in 0.5% Methocel + 0.25% sodium lauryl sulfate (SLS) + 5 mM HCl, a platform formulation frequently used in discovery, a 2-tiered model can be used to correctly predict the stability of 22 of 24 model compounds. First, the model considers the humidity adjusted glass transition temperature of the solid dispersion (Tg,dispersion,100% RH). For compounds where Tg,dispersion,100% RH is >30 °C, the dispersion is typically free from crystallization within 3 hours of preparation, which is attributed to a decrease in molecular mobility. 3 hours was selected as the timeframe between suspension preparation and dosing for the purpose of the present research. For compounds where Tg,dispersion,100% RH is 30 °C, the dispersion is typically free from crystallization within 3 hours of preparation, which is attributed to a decrease in molecular mobility. 3 hours was selected as the timeframe between suspension preparation and dosing for the purpose of the present research. For compounds where Tg,dispersion,100% RH is 1000 to be predicted stable) can be used to successfully predict a 3 hour shelf-life
On the particle formation in spray drying process for bio-pharmaceutical applications: Interrogating a new model via computational fluid dynamics
No full textInsights into Water-Induced Phase Separation in Itraconazole–Hydroxypropylmethyl Cellulose Spin Coated and Spray Dried Dispersions
No full textUnraveling the genomic mosaic of a ubiquitous genus of marine cyanobacteria
No full textBackground: The picocyanobacterial genus Synechococcus occurs over wide oceanic expanses, having colonized most
available niches in the photic zone. Large scale distribution patterns of the different Synechococcus clades (based on 16S rRNA gene markers) suggest the occurrence of two major lifestyles ('opportunists'/'specialists'), corresponding to two distinct broad habitats ('coastal'/'open ocean'). Yet, the genetic basis of niche partitioning is still poorly understood in this
ecologically important group.
Results: Here, we compare the genomes of 11 marine Synechococcus isolates, representing 10 distinct lineages.
Phylogenies inferred from the core genome allowed us to refine the taxonomic relationships between clades by revealing a clear dichotomy within the main subcluster, reminiscent of the two aforementioned lifestyles. Genome size is strongly correlated with the cumulative lengths of hypervariable regions (or 'islands'). One of these, encompassing most genes encoding the light-harvesting phycobilisome rod complexes, is involved in adaptation to changes in light quality and has clearly been transferred between members of different Synechococcus lineages. Furthermore, we observed that two strains (RS9917 and WH5701) that have similar pigmentation and physiology have an unusually high number of genes in common, given their phylogenetic distance.
Conclusion: We propose that while members of a given marine Synechococcus lineage may have the same broad geographical distribution, local niche occupancy is facilitated by lateral gene transfers, a process in which genomic islands
play a key role as a repository for transferred genes. Our work also highlights the need for developing picocyanobacterial systematics based on genome-derived parameters combined with ecological and physiological data
Bridging the gap from ocean models to population dynamics of large marine predators: A model of mid-trophic functional groups
No full textThe modeling of mid-trophic organisms of the pelagic ecosystem is a critical step in linking the coupled physical–biogeochemical models to population dynamics of large pelagic predators. Here, we provide an example of a modeling approach with definitions of several pelagic mid-trophic functional groups. This application includes six different groups characterized by their vertical behavior, i.e., occurrence of diel migration between epipelagic, mesopelagic and bathypelagic layers. Parameterization of the dynamics of these components is based on a temperature-linked time development relationship. Estimated parameters of this relationship are close to those predicted by a model based on a theoretical description of the allocation of metabolic energy at the cellular level, and that predicts a species metabolic rate in terms of its body mass and temperature. Then, a simple energy transfer from primary production is used, justified by the existence of constant slopes in log–log biomass size spectrum relationships. Recruitment, ageing, mortality and passive transport with horizontal currents, taking into account vertical behavior of organisms, are modeled by a system of advection–diffusion-reaction equations. Temperature and currents averaged in each vertical layer are provided independently by an Ocean General Circulation Model and used to drive the mid-trophic level (MTL) model. Simulation outputs are presented for the tropical Pacific Ocean to illustrate how different temperature and oceanic circulation conditions result in spatial and temporal lags between regions of high primary production and regions of aggregation of mid-trophic biomass. Predicted biomasses are compared against available data. Data requirements to evaluate outputs of these types of models are discussed, as well as the prospects that they offer both for ecosystem models of lower and upper trophic levels
Size selectivity of intestinal mucus to diffusing particulates is dependent on surface chemistry and exposure to lipids
No full text<div><p></p><p>Intestinal mucus provides a significant barrier to transport of orally delivered drug carriers, as well as other particulates (e.g. food, microbes). The relative significance of particle size, surface chemistry, and dosing medium to mucus barrier properties is not well characterized, but important in designing delivery systems targeted to the intestinal mucosa. In this study, multiple particle tracking (MPT) was used to study diffusion of 20–500 nm diameter carboxylate- and polyethylene glycol-(PEG-)functionalized polystyrene model carriers through intestinal mucus. The impact of exposure to mucus in buffer versus a partially digested triglyceride mixture was explored. Effective diffusivity of particles in intestinal mucus decreased with an increasing particle size less than and more than theoretically (Stokes–Einstein) expected in a homogenous medium when dosed in buffer and model-fed state intestinal contents, respectively. For example, effective diffusivity decreased 2.9- versus 20-fold with increase in the particle size from 100 to 500 nm when dosed to mucus in buffer versus lipid-containing medium. Functionalization with PEG dramatically decreased sensitivity to lipids in a dosing medium. The results indicate that reduction of particle size may increase particle transport through intestinal mucus barriers, but these effects are strongly dependent on intestinal contents and particle surface chemistry.</p></div
Ichthyoplankton assemblages at three shallow seamounts in the South West Indian Ocean
No full textThe composition and spatial variability of ichthyoplankton assemblages were investigated at three shallow seamounts between latitudes 19°S and 33°S in the South West Indian Ocean (SWIO) – La Pérouse (60 m), an unnamed pinnacle south of Madagascar, referred to hereafter as MAD-Ridge (240 m), and the Walters Shoal seamount (18 m). In all, 299 larvae (23 families, 54 species) were present at La Pérouse, 964 larvae (58 families and 127 species) at MAD-Ridge, and 129 larvae (9 families, 24 species) at the Walters Shoal. Larvae of mesopelagic fish in the families Myctophidae and Gonostomatidae were the most dominant at all three seamounts. All developmental stages were present at each seamount, suggesting the larval pelagic phase of certain species occurs at the seamounts. A ‘seamount effect’ was detected only at MAD-Ridge where larval fish densities were significantly higher at summit stations. Overall, MAD-Ridge had much higher densities of fish larvae (157.0 larvae 100 m−3) than La Pérouse (31.1 larvae 100 m−3) and the Walters Shoal (9.6 larvae 100 m−3). Our study demonstrates that ichthyoplankton communities at shallow seamounts in the SWIO are more influenced by their location relative to a landmass, and to oceanographic features such as currents, mesoscale eddies and water masses than the seamount latitude and topography itself
Assessment of predictive models for characterizing the atomization process in a spray dryer’s bi-fluid nozzle
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Near-field dynamics of high-speed spray dryer coannular two fluid nozzle: Effects of operational conditions and formulations
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