APPLICATION OF ATTENUATED TOTAL REFLECTANCE FTIR SPECTROSCOPY TO THE ANALYSIS OF MIXTURES OF PHARMACEUTICAL POLYMORPHS

Full characterization of the polymorphic content of bulk drug chemical s has become increasingly important in the pharmaceutical industry. A multitude of analytical techniques are commonly employed in this proce ss. In this work the feasibility of the Attenuated Total Reflectance F ourier Transform Infrared Spectroscopy (ATR-FTIR) to the qualitative a nd quantitative analysis of mixtures of polymorphs is investigated usi ng three known polymorphs of ganciclovir as model compounds. Definitiv e identification of all three polymorphs is achieved from their ATR-FT IR spectra obtained from the sample in their native state (no sample p reparation). Quantitation of polymorphic mixtures is carried out using a partial least-squares procedure. Quantitative results obtained with validation samples for both binary and ternary crystal form mixtures clearly demonstrate the strong potential of ATR-FTIR technique for use in quantitative analysis of polymorphic content of bulk pharmaceutica l materials. (C) 1998 Elsevier Science B.V. All rights reserved.