The role of surface energetics in the mixing of powders

The mixing of powders is governed by the presence of interparticulate forces, which are dependent on the surface nature of powders. Surface energy, which provides a measure of the hydrophilic and hydrophobic nature of surfaces, was found to play a significant role in the behaviour of powders in mixes. Preliminary work involved the use of surface energetics to predict the spreading behaviour in binary mixes of iron oxide with three excipients; microcrystalline cellulose, magnesium stearate and titanium dioxide. Subsequent work was carried out on binary and tertiary mixes of an active compound, zamifenacin, with starch and/or lactose. The surface nature of the powders was determined using the Wilhelmy plate (DCA) technique, sessile drop technique (DAT), inverse gas chromatography (IGC) and triboelectric charging. These techniques (except for triboelectric charging) involve the use of non-polar and polar liquids to probe the surfaces of powders. Spreading coefficients determined from the DCA data, correctly predicted the spreading behaviour of powders in binary and tertiary systems of iron oxide, as confirmed by visual inspection and scanning electron microscopy of the mixes. The suitability of each technique in characterising surfaces of pharmaceutical powders was assessed and IGC was found to be superior to the DCA and DAT techniques since IGC relied on the direct interaction between the vapour probes and the powder surface. The interaction parameter (I) derived from IGC and the electrostatic charges developed on charging with stainless steel predicted that the interaction between zamifenacin and starch would be more favourable than between zamifenacin and lactose. These predictions were confirmed by homogeneity studies on binary and tertiary mixes of zamifenacin using high-pressure liquid chromatography and near-infrared spectroscopy (NIRS). NIRS was found to be a good alternative analytical technique for monitoring the mixing of powders, in particular the order of addition of excipients to zamifenacin

Clinical efficacy and safety of a light mask for prevention of dark adaptation in treating and preventing progression of early diabetic macular oedema at 24 months (CLEOPATRA): a multicentre, phase 3, randomised controlled trial

Background: We aimed to assess 24-month outcomes of wearing an organic light-emitting sleep mask as an intervention to treat and prevent progression of non-central diabetic macular oedema. Methods: CLEOPATRA was a phase 3, single-blind, parallel-group, randomised controlled trial undertaken at 15 ophthalmic centres in the UK. Adults with non-centre-involving diabetic macular oedema were randomly assigned (1:1) to wearing either a light mask during sleep (Noctura 400 Sleep Mask, PolyPhotonix Medical, Sedgefield, UK) or a sham (non-light) mask, for 24 months. Randomisation was by minimisation generated by a central web-based computer system. Outcome assessors were masked technicians and optometrists. The primary outcome was the change in maximum retinal thickness on optical coherence tomography (OCT) at 24 months, analysed using a linear mixed-effects model incorporating 4-monthly measurements and baseline adjustment. Analysis was done using the intention-to-treat principle in all randomised patients with OCT data. Safety was assessed in all patients. This trial is registered with Controlled-Trials.com, number ISRCTN85596558. Findings: Between April 10, 2014, and June 15, 2015, 308 patients were randomly assigned to wearing the light mask (n=155) or a sham mask (n=153). 277 patients (144 assigned the light mask and 133 the sham mask) contributed to the mixed-effects model over time, including 246 patients with OCT data at 24 months. The change in maximum retinal thickness at 24 months did not differ between treatment groups (mean change −9·2 μm [SE 2·5] for the light mask vs −12·9 μm [SE 2·9] for the sham mask; adjusted mean difference −0·65 μm, 95% CI −6·90 to 5·59; p=0·84). Median compliance with wearing the light mask at 24 months was 19·5% (IQR 1·9–51·6). No serious adverse events were related to either mask. The most frequent adverse events related to the assigned treatment were discomfort on the eyes (14 with the light mask vs seven with the sham mask), painful, sticky, or watery eyes (14 vs six), and sleep disturbance (seven vs one). Interpretation: The light mask as used in this study did not confer long-term therapeutic benefit on non-centre-involving diabetic macular oedema and the study does not support its use for this indication. Funding: The Efficacy and Mechanism Evaluation Programme, a Medical Research Council and National Institute for Health Research partnership

Side-by-Side Concert Seattle Symphony UW Symphony Orchestra January 26, 2017

Concert ProgramConcert Program for Side-by-Side Concert Seattle Symphony UW Symphony Orchestra January 26, 201