Measurement of Low-Dose Active Pharmaceutical Ingredient in a Pharmaceutical Blend Using Frequency-Domain Photon Migration

Abstract

Frequency-domain photon migration (FDPM) measurements of time-dependent light propagation are conducted to provide the powder absorbance for quantitative prediction of terazosin as the active pharmaceutical ingredient (API) in a low-dose (0.72 wt %) oral tablet formulation. Calibration of the FDPM-derived powder absorbance at discrete wavelengths of 514, 650, 687, and 785nm was performed for API contents ranging between 0 and 1.5 wt % in mixtures showing maximum sensitivity at 650nm. The relative standard deviation (RSD) of FDPM absorption coefficient measurement at 650nm in a well-mixed 1.08 wt % terazosin blend was <1.6%, of which no more than 0.12% arose from FDPM instrumental error and the remainder was attributable to the complete-random-mixture model. The applicability of FDPM as an on-line sensor for powder-blending operations was further evaluated by analyzing grab samples taken directly from five locations of a 2-cu-ft Gallay blender at intervals of 5min within the blending process. FDPM results indicate that homogeneity was largely achieved in the first 10 min, during which the RSD of API content across five sampling locations decreased from 27% to 8%, and the RSD decreased to 5% after 25min of blending. Evolution of homogeneity within the blending process assessed through FDPM measurements was fit to the first-order model of particle blending further evidencing applicability for monitoring powder-blending processes. © 2004 Wiley-Liss, Inc. and the American Pharmacists Association