Lean Raman imaging for rapid assessment of homogeneity in pharmaceutical formulations.

Solid dispersion formulations and drug in polymer matrices are increasingly being used by the pharmaceutical industry to enhance the solubility, or bio-availability, of active pharmaceutical ingredients (APIs). The degree of solubility or bio-availability enhancement, as well as properties such as chemical stability and physical characteristics, will be dependent on the homogeneity of the drug in polymer matrix. The use of Raman spectroscopy to assess homogeneity has traditionally been limited by the time required to acquire images from a statistically representative sample area. This may be overcome by employing a more rapid one-dimensional Raman line-mapping approach and using a statistical analysis to extract the critical information. This approach has been termed "lean" Raman imaging and allows a large area of sample to be probed in a relatively short space of time. This paper discusses the use of "lean" Raman imaging to assess two performance-indicating parameters of a drug in polymer formulation, sedimentation of the API within a capsule formulation and phase separation of the individual components. The development of a screening method, using Raman line mapping to allow rapid measurement of sedimentation of the API, is discussed. This method requires less than half an hour per capsule for data collection and processing. In addition, the development of a "lean" Raman mapping technique, using single line scans to assess drug and polymer domain sizes, is detailed. This technique employs a simple peak ratio approach coupled with statistical analysis to provide a measure of the degree of drug and polymer segregation without the need for acquisition of high pixel density images or multivariate analysis. The Raman mapping data is compared with both the dissolution profiles and processing parameters of the samples tested and a strong correlation is shown between formulation homogeneity and dissolution behavior.