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.
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 approximately 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.
Sasić
Slobodan
S
Pfizer, Analytical Research and Development Groton, Connecticut, USA. slsasic@yahoo.com
Whitlock
Mark
M
D004345:Drug Industry / Q000295:instrumentation / Q000379:methods*; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D013059:Spectrum Analysis, Raman / Q000379:methods; D013607:Tablets / Q000737:chemistry*
D004364:Pharmaceutical Preparations; D013607:Tablets