title: Raman chemical mapping of low-content active pharmaceutical ingredient formulations. III. Statistically optimized sampling and detection of polymorphic forms in tablets on stability.
abstract: Several tablets of a formulation containing 1% w/w of the desired active pharmaceutical ingredient (API) form are spiked with minimal amounts of two different anhydrous polymorphs and an amorphous form. The amount of contaminant form was 2.5 to 10% of the total API concentration (0.025 to 0.1% w/w in the tablet), with five spiked tablets prepared. The presence of these contaminant particles are then identified using Raman microscopy/mapping. The entire surface of each of these tablets is Raman-probed through a grid based on our previous proposal (Šašić, S.; Whitlock, M. Appl. Spectrosc.2008, 62, 916) about the minimal number of spectra to acquire that would guarantee identification of the targeted component (taking into account the limit of detection). All three forms have been clearly identified in the Raman mapping spectra of prepared "calibration" tablets; particularly of note is the 2.5% spike (0.025% w/w in the tablet) of the relatively weakly scattering amorphous form. The same method is then applied to packaged tablets on stability and demonstrates that none of the previously analyzed contaminant forms is detected, hence building confidence that the desired API form does not change during stability testing.
authors.affiliation: Pfizer, Worldwide Research and Development, Groton 06340, Connecticut, United States. slsasic@yahoo.com
authors.forename: Slobodan
authors.initials: S
authors.lastname: Šašić
authors.forename: Shawn
authors.initials: S
authors.lastname: Mehrens
mesh_terms: D004345:Drug Industry / Q000295:instrumentation / Q000379:methods*; D004364:Pharmaceutical Preparations / Q000032:analysis*; D013059:Spectrum Analysis, Raman / Q000379:methods*; D013607:Tablets / Q000737:chemistry*
chemical_list: D004364:Pharmaceutical Preparations; D013607:Tablets