Monitoring Powder Blend Homogeneity Using Light-Induced Fluorescence

Abstract

Abstract. Light-induced fluorescence (LIF) was evaluated as a process analytical technology to monitor blend homogeneity and establish a relationship with high-performance liquid chromatography (HPLC). Secondary aims for this study included a determination of blend steady-state, acceptable mixing time interval, and mixing end point. Also, identification of potential "dead spots" in the 124 L intermediate bulk container mixing tote was explored. Individual samples from 13 sample locations were collected at 0.25, 0.5, 0.75, 1, 2, 5, 10, and 20 min and analyzed using LIF and HPLC. LIF and HPLC methods showed similar mixing profiles. A coefficient of determination (R 2 ) of 0.86 (p value<0.0001) was obtained for a second-degree polynomial bivariate fit of LIF counts by HPLC percent label claim (%LC). A significant linear relationship was determined between LIF percent relative standard (%RSD) and HPLC %RSD (R 2 =0.97, p<0.0001). The LIF steady-state, acceptable mixing time interval, and mixing end point were determined to be 1-20, 2-20, and 2 min, respectively. The steady-state, acceptable mixing time interval, and mixing end point determined by HPLC were 1-20, 5-10, and 5 min, respectively. The Tukey-Kramer honestly significant difference analysis of HPLC %LC by sample location at 5 and 10 min mixing times showed that there was a statistical difference between the HPLC %LC group means at two blender locations.

Application of fluorescent markers for homogeneity assessment of grain mixtures based on maize content

“…Among the variety of tools, particular attention was paid to the methods using the fluorescence phenomenon and image analysis. These instruments are used in the following industrial sectors: food, agricultural, pharmaceutical and chemical industries (Berthiaux et al, 2006, Coppeta et al, 1995Dauman et al, 2008;Karumanchi et al, 2011;Lai et al, 2001;Matuszek, 2015;Realpe et al, 2003;Zelko et al, 2012).…”

Macro-Raman spectroscopy for bulk composition and homogeneity analysis of multi-component pharmaceutical powders

“…Homogeneity of the final blend after mixing depends on many Page 8 of 43 A c c e p t e d M a n u s c r i p t 7 parameters such as mixing method, mixer operating parameters, and component concentrations [27][28][29]. The tendency of a powder mixture to either form a consistent blend or to separate depends mostly on physical properties such as cohesiveness, particle size distribution, particle density, electrostatic charge and other surface properties [30][31][32][33][34].…”

“…High-performance liquid chromatography has been widely used as a standard off-line reference method for homogeneity analysis [44,45]. Non-invasive techniques such as near-infrared (NIR) spectroscopy [46][47][48][49][50][51][52] and chemical imaging [53][54][55], Raman spectroscopy [56][57][58], and lightinduced fluorescence [31,59] are also widely used for on-line or in-line measurement of blend uniformity. Of the large number of publications describing such techniques for blend uniformity Page 9 of 43 A c c e p t e d M a n u s c r i p t 8 analysis, however, few have noted the impact of effective sample volume on homogeneity analysis.…”

Effect of Percent Relative Humidity, Moisture Content, and Compression Force on Light-Induced Fluorescence (LIF) Response as a Process Analytical Tool

“…Previous studies have shown that LIF can be used in pharmaceutical blending to determine the blending end point (1,10). Karumanchi et al (10) used off-line LIF to determine blend uniformity, mixing end point, and identification of mixer dead-spots for a commercial scale blending operation. This technique has also shown to be promising in nondestructively measuring online active pharmaceutical ingredient (API) tablet concentration (11,12).…”