AAAR 35th Annual Conference October 17 - October 21, 2016 Oregon Convention Center Portland, Oregon, USA
Abstract View
Low Frequency Shift Macro-Raman Spectroscopy for Analysis of Non-uniform Multi-component Powders
Hui Wang, Lisa Williams, Susan Hoe, David Lechuga-Ballesteros, David Barona, REINHARD VEHRING, University of Alberta
Abstract Number: 309 Working Group: Instrumentation and Methods
Abstract Pharmaceutical aerosols are frequently generated from powder mixtures that may consist of different chemical components with varying particle size. Macro-Raman spectroscopy is capable of analyzing the composition, and in the low frequency shift version, also the solid phase of individual aerosol particles. This study presents a newly developed macro-Raman spectrometer for quantitative analysis of multi-component, non-uniform bulk powder samples that are impractical to measure with micro-Raman spectroscopy. Pointwise measurement utilizing a 2mm conical cavity sample holder and continuous scanning along a 5mm groove cavity sample holder were used. The effective sampling volume of the macro-Raman system during static pointwise measurement was determined to be about 0.1μL by comparing the uncertainty of measured powder compositions of two commercial lactose-carrier based dry powder inhalers Flixotide® (250μg fluticasone / dose) and Seretide® (50μg salmeterol + 500μg fluticasone / dose) with Monte-Carlo simulations. Binary mixtures (1:1 by mass) of L-leucine (ACROS) and D-mannitol (Sigma-Aldrich) particles were mixed using a wrist action shaker for 1, 2, 5, and 10 hours and measured using both point-by-point and scanning methods. The spatial uniformity of the powder mixtures was characterized by the standard deviation of pointwise measured compositions. The uniformity decreased with longer mixing time, indicating that this is not an effective method of mixing powders with small particle size. However, both the mean value of 20 pointwise measured compositions and the composition derived from a single scan along the groove sample holder agreed with the nominal composition. Thus, macro-Raman spectroscopy with sample scanning achieves a greatly increased sampling volume and decreases sampling error in non-uniform powder samples. Also, spatial variability in sample compositions can be analyzed to evaluate the level of mixing of multi-component powder samples.