Towards a Framework for Evaluating and Reporting Hansen Solubility Parameters: Applications to Nano and Micron Scale Particle Dispersions

<p>A thorough understanding of complex interactions within particulate systems is a key for knowledge-based formulations. Hansen solubility parameters (HSP) are widely used to assess the compatibility of the dispersed phase with the continuous phase. At present, the determination of HSP is often based on a liquid ranking list obtained by evaluating a pertinent dispersion parameter using only one pre-selected characterization method. Furthermore, one cannot rule out the possibility of subjective judgment especially for liquids for which it is difficult to decipher the compatibility or underlying interactions. As a result, the end value of HSP might be of little or no information. To overcome these issues, we introduce a generalized technology-agnostic combinatorics-based approach. We discuss the principles of the approach and the implications of evaluating and reporting particle HSP values. We demonstrate the approach by using SiN_x particles synthesized in the gas phase. We leverage the analytical centrifugation data to evaluate stability trajectories of SiN_x dispersions in various liquids to deduce particle-liquid compatibility. </p>

Towards a Framework for Evaluating and Reporting Hansen Solubility Parameters: Applications to Nano and Micron Scale Particle Dispersions

<p>A thorough understanding of complex interactions within particulate systems is a key for knowledge-based formulations. Hansen solubility parameters (HSP) are widely used to assess the compatibility of the dispersed phase with the continuous phase. At present, the determination of HSP is often based on a liquid ranking list obtained by evaluating a pertinent dispersion parameter using only one pre-selected characterization method. Furthermore, one cannot rule out the possibility of subjective judgment especially for liquids for which it is difficult to decipher the compatibility or underlying interactions. As a result, the end value of HSP might be of little or no information. To overcome these issues, we introduce a generalized technology-agnostic combinatorics-based approach. We discuss the principles of the approach and the implications of evaluating and reporting particle HSP values. We demonstrate the approach by using SiN_x particles. We leverage the analytical centrifugation data to evaluate stability trajectories of SiN_x dispersions in various liquids to deduce particle-liquid compatibility. </p>

Towards a Framework for Evaluating and Reporting Hansen Solubility Parameters: Applications to Nano and Micron Scale Particle Dispersions

<p>A thorough understanding of complex interactions within particulate systems is a key for knowledge-based formulations. Hansen solubility parameters (HSP) are widely used to assess the compatibility of the dispersed phase with the continuous phase. At present, the determination of HSP is often based on a liquid ranking list obtained by evaluating a pertinent dispersion parameter using only one pre-selected characterization method. Furthermore, one cannot rule out the possibility of subjective judgment especially for liquids for which it is difficult to decipher the compatibility or underlying interactions. As a result, the end value of HSP might be of little or no information. To overcome these issues, we introduce a generalized technology-agnostic combinatorics-based approach. We discuss the principles of the approach and the implications of evaluating and reporting particle HSP values. We demonstrate the approach by using SiN_x particles. We leverage the analytical centrifugation data to evaluate stability trajectories of SiN_x dispersions in various liquids to deduce particle-liquid compatibility. </p>

Function of Hemoglobin-Based Oxygen Carriers: Determination of Methemoglobin Content by Spectral Extinction Measurements

Suspensions of hemoglobin microparticles (HbMPs) are promising tools as oxygen therapeutics. For the approval of clinical studies extensive characterization of these HbMPs with a size of about 750 nm is required regarding physical properties, function, pharmaco-kinetics and toxicology. The standard absorbance measurements in blood gas analyzers require dissolution of red blood cells which does not work for HbMP. Therefore, we have developed a robust and rapid optical method for the quality and functionality control of HbMPs. It allows simultaneous determination of the portion of the two states of hemoglobin oxygenated hemoglobin (oxyHb) and deoxygenated hemoglobin (deoxyHb) as well as the content of methemoglobin (metHb). Based on the measurement of collimated transmission spectra between 300 nm and 800 nm, the average extinction cross section of HbMPs is derived. A numerical method is applied to determine the composition of the HbMPs based on their wavelength-dependent refractive index (RI), which is a superposition of the three different states of Hb. Thus, light-scattering properties, including extinction cross sections can be simulated for different compositions and sizes. By comparison to measured spectra, the relative concentrations of oxyHb, deoxyHb, metHb are accessible. For validation of the optically determined composition of the HbMPs, we used X-ray fluorescence spectrometry for the ratio of Fe(II) (oxyHb/deoxyHb) and Fe(III) (metHb). High accuracy density measurements served to access heme-free proteins, size was determined by dynamic light scattering and analytical centrifugation and the shape of the HbMPs was visualized by electron and atomic force microscopy.

Probing sedimentation non-ideality of particulate systems using analytical centrifugation

A comprehensive experimental methodology based on analytical centrifugation is presented for the characterization of hydrodynamic non-ideality of colloidal particles.

Plasma glutathione status as indicator of pre-analytical centrifugation delay

Prolonged incubation of blood prior to plasma preparation can significantly influence the quality of the resulting data. Different markers for this pre-clinical variability have been proposed over the years but with limited success. In this study we explored the usefulness of glutathione (GSH) status, namely ratio of reduced to oxidized glutathione (GSH/GSSG), as potential marker of plasma preparation delay. For that purpose, blood from 20 healthy volunteers was collected into tubes with a cysteine quencher (N-ethylmaleimide; NEM) for GSH stabilization. Plasma preparation was delayed at room temperature for up to 3 hours and every hour, a plasma sample was prepared and the GSH/GSSG ratio measured. We report that over the course of the investigation, plasma concentrations of both GSH and GSSG increased linearly (R2 = 0.99 and 0.98, respectively). Since GSH increased at a much faster rate compared to GSSG, the GSH/GSSG ratio also increased linearly in a time dependent manner (R2 = 0.99). As GSH is an intracellular antioxidant, we speculated that this might stem from ongoing blood hemolysis, which was confirmed by the time dependent rise in lactate dehydrogenase (LDH) activity in the plasma samples. Moreover, we demonstrate that the addition of the thiol alkylating reagent NEM directly to the blood tubes does not seem to influence downstream analysis of clinical parameters. In conclusion we propose that the glutathione status could be used as an indicator of the centrifugation delay prior to plasma preparation.

Exhibitive Nano-to-Micron Scale Sedimentation Dynamics of Colloidal Formulations Through Direct Visualization

The study of sedimentation behavior of nanoparticle dispersions is important for revealing particle size and colloidal stability characteristics. Quantitative appraisal of real-world colloidal systems in their native state, is key for replacing prevailing empiricism in formulation science by knowledge-based design. Herein, we choose fuel cell inks as one case-example amongst many other possibilities to present a new visualization technique, called <i>Transmittogram</i>. This technique readily depicts the time-resolved settling behavior of solid-liquid dispersions, measured by analytical centrifugation (AC). Although AC enables the causal examination of agglomeration, settling, and creaming behavior of dispersions, along with its consequent effect on structure formation and product properties, the understanding of the main transmission readout is often non-intuitive and complex. Transmittograms are, therefore, the missing link for straightforward data interpretation. First, we illustrate the utility of transmittogram analysis using model silica nanoparticle systems and further validate it against known characteristics of the system. Then, we demonstrate the application of transmittograms to characterize fuel cell inks, showing the strength of the approach in deconvoluting and distilling information to the reader. Finally, we discuss the potential of the technique for routine analysis using analytical centrifugation.<br>

Exhibitive Nano-to-Micron Scale Sedimentation Dynamics of Colloidal Formulations Through Direct Visualization

The study of sedimentation behavior of nanoparticle dispersions is important for revealing particle size and colloidal stability characteristics. Quantitative appraisal of real-world colloidal systems in their native state, is key for replacing prevailing empiricism in formulation science by knowledge-based design. Herein, we choose fuel cell inks as one case-example amongst many other possibilities to present a new visualization technique, called <i>Transmittogram</i>. This technique readily depicts the time-resolved settling behavior of solid-liquid dispersions, measured by analytical centrifugation (AC). Although AC enables the causal examination of agglomeration, settling, and creaming behavior of dispersions, along with its consequent effect on structure formation and product properties, the understanding of the main transmission readout is often non-intuitive and complex. Transmittograms are, therefore, the missing link for straightforward data interpretation. First, we illustrate the utility of transmittogram analysis using model silica nanoparticle systems and further validate it against known characteristics of the system. Then, we demonstrate the application of transmittograms to characterize fuel cell inks, showing the strength of the approach in deconvoluting and distilling information to the reader. Finally, we discuss the potential of the technique for routine analysis using analytical centrifugation.<br>