Effective mass sampled by NIR fiber-optic reflectance probes in blending processes

Recent efforts have demonstrated the in situ use of NIR spectroscopy to determine the homogeneity and potency of powder blends. This work has raised questions regarding the effective mass of a powder blend interrogated by a fiber-optic probe. The effective mass determined from experiments described herein is wavelength dependent and ranges from 0.154 to 0.858 g with a maximum standard deviation of about 0.16 g. Although the precision of this estimate is low, it is sufficiently accurate to demonstrate the usefulness of in situ NIR monitoring of blending operations in the pharmaceutical industry. The method was established by using the relationship between sample mass and spectral variance. Mixtures of lactose (50% w/w), microcrystalline cellulose (40% w/w), and sodium benzoate (10% w/w) were manually blended and sampled at selected intervals. The spectral variance at relevant wavelengths was determined as a function of blend homogeneity and sample mass using a standard micro-sample cup. The spectral variance obtained from micro-cup measurements was used to calibrate the effective mass sampled by a fiber-optic reflectance probe. The estimated mass was greatest at wavelengths where the minor constituent contributed most to the overall spectral variance. Typical pharmaceutical tablets have weights in the range of 0.1–1.0 g. According to FDA regulations, the maximum allowed sample mass for determining the homogeneity of these preparations is 0.3–3.0 g. For many formulations, the effective mass sampled by the fiber-optic probe easily falls below this range.