[Simple method for quantitative determination of active polymorphous and amorphous drugs in drug products by fourier...

The feasibility of a simple Fourier transform (FT)-Raman spectroscopic method for the quantitative determination of unexpected active drug polymorphs or amorphous in drug products was explored. In this study, calibration samples were prepared by physically mixing drug substances with their polymorphs or amorphous, without using excipients. A partial least-squares (PLS) method was applied to the quantitative analysis of the FT-Raman spectra obtained. As model drug products, compound A drug substances (form alpha) containing several ratios of polymorph, (form beta), were physically mixed with excipients to prepare powder samples corresponding to compound A tablets (30 and 120 mg). The mixture of compound B, form I and amorphous, were also mixed with excipients to mimic powdered compound B tablets (32 mg). Satisfactory relationships between the theoretical contents of polymorph or amorphous and determined contents were obtained; quantitation limits were 5-10%. In the case of powder samples corresponding to compound A tablets (30 mg) and compound B tablets (32 mg), differentiating the FT-Raman spectra prior to PLS analysis was required to improve the precision of the determinations.