Raman Mapping of Low-Content Active-Ingredient Pharmaceutical Formulations. Part II: Statistically Optimized Sampling for Detection of Less Than 1% of an Active Pharmaceutical Ingredient

摘要

Several tablets are prepared with two forms of an active pharmaceutical ingredient (API) of which one (less than 1% w/w) is considered undesirable. The presence of this component is tested for by Raman microscopy in a series of mapping experiments. These experiments are conducted with a statistically based sampling routine in which the number of spectra to collect across the whole surface of a tablet is set so as to theoretically ensure spectral detection of the low-concentration form. Such experiments are then repeated a number of times to achieve ∼95% confidence that the strictly limited number of sampling points suffice to detect the low-concentration form and that Raman microscopy is technically a reliable method for analytical analysis of this type.