Discriminating Between Polymorphs Of Acetaminophen Using Morphologically-Directed Raman Spectroscopy (MDRS)

Interest in studying mixed systems of pharmaceutical relevance is not a new concept. From intrinsic polymorphism to complex final products, the challenges encountered by modern analytical scientists have multiplied both in number and in complexity. Established techniques are often unable to provide both separation and identification of species in a mixed system, as they are used to probe chemistry (bulk spectroscopy), or individual particle characteristics (microscopy and SEM). Combining techniques capable of analyzing micronscale particulates with absolute chemical specificity provides a new window into describing the complicated mixtures common in today’s competitive pharmaceutical market.

Malvern Instruments’ Morphologi G3-ID provides just such a technology combination, uniting automated microscopy and spectroscopy in an integrated package. This partnering of techniques has been termed Morphology-Directed Raman Spectroscopy (MDRS). Raman spectroscopy is sensitive to the unique polymorphic forms of a substance, and can be used to investigate single particles to assist in determining the long-term stability of a product. Correlations may be established between morphological and spectroscopic results, where morphologically-distinct particle groups are found to share common spectra, and vice versa. The ability of MDRS to target particles of distinct morphology for Raman investigation provides added sensitivity to the measurement, as spectra for particles that are not of interest are not measured. Likewise, knowing that a group of particles with similar spectra may be described by a common morphology allows the analyst to assess particulate quantity in the absence of measuring a spectrum for each particle in the morphologically-similar group. Such correlations between particle morphology and chemical identity allow MDRS to provide an improvement in efficiency over manual methods.