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Characterization of wet-milled drug suspensions containing neutral polymer-anionic surfactant as stabilizers poses unique challenges in terms of assessing the aggregation state and examining the stabilization mechanisms. Using a multi-faceted characterization method, this study aims to assess the aggregation state of wet-milled griseofulvin (GF) nanosuspensions and elucidate the stabilization mechanisms and impact of stabilizers. Two grades, SSL and L, of hydroxypropyl cellulose (HPC) with molecular weights of 40 and 140 kg/mol, respectively, were used as a neutral stabilizer at concentrations varying from 0 to 7.5% (w/w) without and with 0.05% (w/w) sodium dodecyl sulfate (SDS). The aggregation state was examined via laser diffraction, scanning electron microscope (SEM) imaging, and rheometry. Zeta potential, stabilizer adsorption, surface tension, and drug wettability were used to elucidate the stabilization mechanisms. The results suggest that deviation from a uni-modal PSD and pronounced pseudoplasticity with power-law index lower than one signify severe aggregation. Polymer or surfactant alone was not able to prevent GF nanoparticle aggregation, whereas HPC-SDS combination led to synergistic stabilization. The effect of polymer concentration was explained mainly by the stabilizer adsorption and partly by surface tension. The synergistic stabilization afforded by HPC-SDS, traditionally explained by electrosteric mechanism, was attributed to steric stabilization provided by HPC and enhanced GF wettability/reduced surface tension provided by SDS. Zeta potential results could not explain the mitigation of aggregation by HPC-SDS. Overall, this study has demonstrated that the elucidation of the complex effects of HPC-SDS on GF nanosuspension stability entails a multi-faceted and comprehensive characterization approach.

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An efficient numerical algorithm based on the convolution of functions and on finite difference approximations for the diffusion equation is utilized to determine the quantity of calcium ions (Ca 2+ ) participating in unitary Ca 2+ release events, termed "Ca 2+ sparks", in heart muscle. Output images of localized increases in cytosolic Ca 2+ concentration ([Ca 2+ ]), due predominantly to Ca 2+ release from intracellular storage sites, are obtained using fluorescent calcium indicators and confocal microscopy. To obtain the quantity of Ca 2+ underlying these localized increases of cytosolic [Ca 2+ ], one-dimensional output images are deconvolved with a point spread function that describes the optical properties of the microscope. The resulting input image is then reconstructed, assuming symmetry, in a threedimensional image of [Ca 2+ ] and all Ca 2+ -bound species. Temporal information about free and bound Ca 2+ species can be obtained by performing convolutions on a series of output images recorded in time and then accounting for the kinetics of Ca 2+ interactions with the fluorescent calcium indicator and other Ca 2+ binding species. The effect of microscope imaging properties on measurements of local [Ca 2+ ] and the ability to reconstruct the underlying changes in Ca 2+ species during a Ca 2+ spark are presented.