Water-Induced Phase Separation of Spray-Dried Amorphous Solid Dispersions.

Spray drying is widely used in the manufacturing of amorphous solid dispersion (ASD) systems due to its fast drying rate, enabling kinetic trapping of the drug in amorphous form. Spray-drying conditions, such as solvent composition, can have a profound impact on the properties of spray-dried dispersions. In this study, the phase behavior of spray-dried dispersions from methanol and methanol-water mixtures was assessed using ritonavir and copovidone [poly(vinylpyrrolidone-co-vinyl acetate) (PVPVA)] as dispersion components. The resultant ASDs were characterized using differential scanning calorimetry (DSC), fluorescence spectroscopy, X-ray photoelectron spectroscopy (XPS), as well as surface-normalized dissolution rate (SNDR) measurements. Quaternary phase diagrams were calculated using a four-component Flory-Huggins model. It was found that the addition of water to the solvent system can lead to phase separation during the spray-drying process. A 10:90 H2O/MeOH solvent system caused a minor extent of phase separation. Phase heterogeneity in the 50 and 75% drug loading ASDs prepared from this spray solvent can be detected using DSC but not with other techniques used. The 25% drug loading system did not show phase heterogeneity in solid-state characterization but exhibited a compromised dissolution rate compared to that of the miscible ASD prepared from H2O-free solvent. This is possibly due to the formation of slow-releasing drug-rich phases upon phase separation. ASDs prepared with a 60:40 H2O/MeOH solvent mixture showed phase heterogeneity with all analytical methods used. The surface composition of dispersion particles as measured by fluorescence spectroscopy and XPS showed good agreement, suggesting surface drug enrichment of the spray-dried ASD particles prepared from this solvent system. Calculated phase diagrams and drying trajectories were consistent with experimental observations, suggesting that small variations in solvent composition may cause significant changes in ASD phase behavior during drying. These findings should aid in spray-drying process development for ASD manufacturing and can be applied broadly to assess the risk of phase separation for spray-drying systems using mixed organic solvents or other solvent-based processes.

Recent Trends in Compressive Raman Spectroscopy Using DMD-Based Binary Detection.

The collection of high-dimensional hyperspectral data is often the slowest step in the process of hyperspectral Raman imaging. With the conventional array-based Raman spectroscopy acquiring of chemical images could take hours to even days. To increase the Raman collection speeds, a number of compressive detection (CD) strategies, which simultaneously sense and compress the spectral signal, have recently been demonstrated. As opposed to conventional hyperspectral imaging, where full spectra are measured prior to post-processing and imaging CD increases the speed of data collection by making measurements in a low-dimensional space containing only the information of interest, thus enabling real-time imaging. The use of single channel detectors gives the key advantage to CD strategy using optical filter functions to obtain component intensities. In other words, the filter functions are simply the optimized patterns of wavelength combinations characteristic of component in the sample, and the intensity transmitted through each filter represents a direct measure of the associated score values. Essentially, compressive hyperspectral images consist of 'score' pixels (instead of 'spectral' pixels). This paper presents an overview of recent advances in compressive Raman detection designs and performance validations using a DMD based binary detection strategy.

Binary Complementary Filters for Compressive Raman Spectroscopy.

The previously described optimized binary compressive detection (OB-CD) strategy enables fast hyperspectral Raman (and fluorescence) spectroscopic analysis of systems containing two or more chemical components. However, each OB-CD filter collects only a fraction of the scattered photons and the remainder of the photons are lost. Here, we present a refinement of OB-CD, the OB-CD2 strategy, in which all of the collected Raman photons are detected using a pair of complementary binary optical filters that direct photons of different colors to two photon counting detectors. The OB-CD2 filters are generated using a new optimization algorithm described in this work and implemented using a holographic volume diffraction grating and a digital micromirror device (DMD) whose mirrors are programed to selectively direct photons of different colors either to one or the other photon-counting detector. When applied to pairs of pure liquids or two-component solid powder mixtures, the resulting OB-CD2 strategy is shown to more accurately estimate Raman scattering rates of each chemical component, when compared to the original OB-CD, thus facilitating chemical classification at speeds as fast as 3 µs per measurement and the collection of Raman images in under a second.

Fluorescence modeling for optimized-binary compressive detection Raman spectroscopy.

The recently-developed optimized binary compressive detection (OB-CD) strategy has been shown to be capable of using Raman spectral signatures to rapidly classify and quantify liquid samples and to image solid samples. Here we demonstrate that OB-CD can also be used to quantitatively separate Raman and fluorescence features, and thus facilitate Raman-based chemical analyses in the presence of fluorescence background. More specifically, we describe a general strategy for fitting and suppressing fluorescence background using OB-CD filters trained on third-degree Bernstein polynomials. We present results that demonstrate the utility of this strategy by comparing classification and quantitation results obtained from liquids and powdered mixtures, both with and without fluorescence. Our results demonstrate high-speed Raman-based quantitation in the presence of moderate fluorescence. Moreover, we show that this OB-CD based method is effective in suppressing fluorescence of variable shape, as well as fluorescence that changes during the measurement process, as a result of photobleaching.