Analysis and prediction of defects in UV photo-initiated polymer microarrays

Polymer microarrays are a key enabling technology for the discovery of novel materials. This technology can be further enhanced by expanding the combinatorial space represented on an array. However, not all materials are compatible with the microarray format and materials must be screened to assess their suitability with the microarray manufacturing methodology prior to their inclusion in a materials discovery investigation. In this study a library of materials expressed on the microarray format are assessed by light microscopy, atomic force microscopy and time-of-flight secondary ion mass spectrometry to identify compositions with defects that cause a polymer spot to exhibit surface properties significantly different from a smooth, round, chemically homogeneous ‘normal’ spot. It was demonstrated that the presence of these defects could be predicted in 85% of cases using a partial least square regression model based upon molecular descriptors of the monomer components of the polymeric materials. This may allow for potentially defective materials to be identified prior to their formation. Analysis of the PLS regression model highlighted some chemical properties that influenced the formation of defects, and in particular suggested that mixing a methacrylate and an acrylate monomer and/or mixing monomers with long and linear or short and bulky pendant groups will prevent the formation of defects. These results are of interest for the formation of polymer microarrays and may also inform the formulation of printed polymer materials generally.Burroughs Wellcome Fund (grant number 085245)Royal Society (Great Britain) (Wolfson Research Merit Award

Rapid nano-gram scale screening method of micro-arrays to evaluate drug-polymer blends using high-throughput printing technology

A miniaturized, high-throughput assay was optimized to screen polymer-drug solid dispersions using a 2-D Ink-jet printer. By simply printing nanoliter amounts of polymer and drug solutions onto an inert surface, drug:polymer micro-dots of tunable composition were produced in an easily-addressable micro-array format. The amount of material printed for each dried spot ranged from 25 ng to 650 ng. These arrays were used to assess the stability of drug:polymer dispersions with respect to recrystallization, using polarized light microscopy. One array with a panel of 6 drugs formulated at different ratios with Poly (vinylpyrrolidone-vinyl acetate) copolymer (PVPVA) was developed to estimate a possible bulk (gram-scale) approximation threshold from the final printed nano amount of formulation. Another array was printed at a fixed final amount of material to establish a literature comparison of one drug formulated with different commercial polymers for validation. This new approach may offer significant efficiency in pharmaceutical formulation screening, with each experiment in the nano-micro-array format requiring from 3 up to 6 orders of magnitude lower amounts of sample than conventional screening methods

Dichloro[(eta(5)-cyclopentadienyl)dimethyl(eta(5)-3-phenylindenyl)silane]hafnium(IV) : a powder study

Peer reviewe

Strategies for MCR image analysis of large hyperspectral data-sets

Polymer microarrays are a key enabling technology for high throughput materials discovery. In this study, multivariate image analysis, specifically multivariate curve resolution (MCR), is applied to the hyperspectral time of flight secondary ion mass spectroscopy (ToF-SIMS) data from eight individual microarray spots. Rather than analysing the data individually, the data-sets are collated and analysed as a single large data-set. Desktop computing is not a practical method for undertaking MCR analysis of such large data-sets due to the constraints of memory and computational overhead. Here, a distributed memory High-Performance Computing facility (HPC) is used. Similar to what is achieved using MCR analysis of individual samples, the results from this consolidated data-set allow clear identification of the substrate material; furthermore, specific chemistries common to different spots are also identified. The application of the HPC facility to the MCR analysis of ToF-SIMS hyperspectral data-sets demonstrates a potential methodology for the analysis of macro-scale data without compromising spatial resolution (data ‘binning’

Strategies for MCR image analysis of large hyperspectral data-sets

Polymer microarrays are a key enabling technology for high throughput materials discovery. In this study, multivariate image analysis, specifically multivariate curve resolution (MCR), is applied to the hyperspectral time of flight secondary ion mass spectroscopy (ToF-SIMS) data from eight individual microarray spots. Rather than analysing the data individually, the data-sets are collated and analysed as a single large data-set. Desktop computing is not a practical method for undertaking MCR analysis of such large data-sets due to the constraints of memory and computational overhead. Here, a distributed memory High-Performance Computing facility (HPC) is used. Similar to what is achieved using MCR analysis of individual samples, the results from this consolidated data-set allow clear identification of the substrate material; furthermore, specific chemistries common to different spots are also identified. The application of the HPC facility to the MCR analysis of ToF-SIMS hyperspectral data-sets demonstrates a potential methodology for the analysis of macro-scale data without compromising spatial resolution (data ‘binning’

Digital Bridges Across Disciplinary, Practical and Pedagogical Divides: An Online Professional Master’s Program in Heritage Resource Management

Growth and diversification in heritage resource management (HRM) archaeology since the 1960s have created new demands for training the next generations of HRM leaders and for addressing persistent and counterproductive divisions between academic and applied archaeologies. The Simon Fraser University Department of Archaeology (SFU) has responded to these demands with an all-new, cohort-based, thesis-focused graduate program created by and for HRM professionals. The program’s target audience is HRM practitioners who hold Bachelor’s credentials, have initiated promising careers in HRM, and desire advanced, research-focused degrees to enable their professional capacity and upward mobility. The SFU program is structured and focused to provide intensive, predominantly online training in the four essential dimensions of HRM: law and policy, ethics and practice, business management, and research design and methods. The program has been successful through initial cohort cycles and in attracting HRM industry interest in collaboration. Industry-academic partnerships in cognate disciplines have proved effective in comparable circumstances but remain underdeveloped as bases for planning and delivering state-of-the-art training in applied archaeology and the broader field of HRM. Critical next steps in program development entail the identification of attributes of HRM futures desired by all or most HRM stakeholders and the collaborative pursuit of those desired futures

Thermal Behavior of Benzoic Acid/Isonicotinamide Binary Cocrystals

© 2015 American Chemical Society. A comprehensive study of the thermal behavior of the 1:1 and 2:1 benzoic acid/isonicotinamide cocrystals is reported. The 1:1 material shows a simple unit cell expansion followed by melting upon heating. The 2:1 crystal exhibits more complex behavior. Its unit cell first expands upon heating, as a result of C-H⋯π interactions being lengthened. It then is converted into the 1:1 crystal, as demonstrated by significant changes in its X-ray diffraction pattern. The loss of 1 equiv of benzoic acid is confirmed by thermogravimetric analysis-mass spectrometry. Hot stage microscopy confirms that, as intuitively expected, the transformation begins at the crystal surface. The temperature at which conversion occurs is highly dependent on the sample mass and geometry, being reduced when the sample is under a gas flow or has a greater exposed surface area but increased when the heating rate is elevated. (Figure Presented)

Application of biorelevant saliva-based dissolution for optimisation of orally disintegrating formulations of felodipine

The oral cavity is of great importance to the performance of orally retained formulations, including: orally disintegrating tablets, taste-masked formulations, and buccal/sublingual delivery systems. With regards to in vitro dissolution assessment of these dosage forms, human saliva should be represented by the dissolution media. Currently there is no general consensus regarding oral cavity dissolution. In this study pooled human saliva was characterised and utilised as dissolution media for biorelevant oral cavity dissolution studies and to assess drug release. Lipophilic drug felodipine with challenging biopharmaceutical properties was selected for assessment in oral cavity dissolution studies. These saliva dissolution studies investigated for the first time how biorelevant dissolution can be implemented as a screening tool to guide the formulation development process and to predict dosage form performance within the mouth. In this study a combination of three dissolution enhancement strategies (cryomilling, solid dispersion, and inclusion complexation) were employed to eventually increase the concentration of felodipine in saliva 150-fold. Using this successful formulation strategy orally disintegrating tablets of felodipine were produced. Interestingly, the percentage release of felodipine in compendial dissolution apparatus was shown to be over 80% after 10 minutes. On the other hand, salivabased dissolution showed that percentage release of felodipine was only 0.2% after 10 minutes using the same formulation. This discrepancy in drug release between dissolution media highlights the need for biorelevant dissolution apparatus for the oral cavity to reliably assess performance of relevant dosage forms in vitro

Effect of Excipients on Salt Disproportionation during Dissolution: A Novel Application of In Situ Raman Imaging

We have employed a bespoke setup combining confocal Raman microscopy and an ultraviolet–visible (UV–Vis) spectroscopy flow cell to investigate the effect of excipients on the disproportionation kinetics of Pioglitazone HCl (PioHCl) in tablets during dissolution. Three binary formulations of PioHCl, containing citric acid monohydrate (CA), lactose monohydrate (LM), or magnesium stearate (MgSt), respectively, were used as models to study the influence of excipients’ physicochemical properties on the rate of salt disproportionation kinetics and dissolution performance in different aqueous pH environments. It was found that formulation excipients can induce or prevent salt disproportionation by modulating the microenvironmental pH regardless of the pH of the dissolution media. Incorporating CA in PioHCl tablets preserves the salt form and enhances the dissolution performance of the salt in the acidic medium (pH = 1.2). In contrast, LM and MgSt had a detrimental effect on in vitro drug performance by inducing salt disproportionation in the tablet during dissolution in the same acidic medium. Dissolution in the neutral medium (pH = 6.8) showed rapid formation of the free base upon contact with the dissolution medium. The Raman maps of the cross-sectioned tablets revealed the formation of a shell consisting of the free base around the edge of the tablet. This shell decreased the rate of penetration of the dissolution medium into the tablet, which had significant implications on the release of the API into the surrounding solution, as shown by the UV–vis absorption spectroscopy drug release data. Our findings highlight the utility of the Raman/UV–vis flow cell analytical platform as an advanced analytical technique to investigate the effect of excipients and dissolution media on salt disproportionation in real time. This methodology will be used to enhance our understanding of salt stability studies that may pave the way for more stable multicomponent formulations

d-Xylose oxetane copolymers as bioderived and tuneable polyesters for amorphous solid dispersions

The ring-opening copolymerisation of cyclic anhydrides with an oxetane derived from natural monosaccharide D-xylose has been used to synthesise fully biobased water soluble polyesters, which are able to stabilise the amorphous phases of nifedipine and mefenamic acid, enhancing their apparent solubility in water up to 918 and 142% respectively. 2D picolitre-scale inkjet-printing, coupled with polarised optical microscopy (POM) analysis, enabled an initial, high-throughput miniaturised (ng–μg scale) screening of drug formulations. The best formulations were scaled up and analysed by FT-IR spectroscopy and DSC, revealing interactions between the drugs and polymers. Finally, drug dissolution studies demonstrated the effectiveness of the polymers in improving the drugs’ apparent solubility in water. These results showcase the potential of synthetic carbohydrate polymers as excipient for tailored drug formulations