During this recent webinar, Dr. Oksana Olkhovyk presented on the benefits of this novel method of particle sizing that automatically measures particle size distribution. She also discussed specific references to FDA bioequivalence guidance documentation, innovative product design and intellectual property benefits.
We received a number of questions during the webinar, below you can find the transcribed Q&A and download the presentation.
Download Presentation: Ingredient-Specific Particle Sizing Using Raman Chemical Imaging
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- If a sample is wet, how does the solvent affect the results?
In ISPS, we adopt sample preparation methodology used for assessment of drug PSD in suspension formulations by optical microscopy. Solvent does not affect ISPS results since most solvents are weak Raman scatters (i.e. water). Raman scattering from most of the solvent is negligible in the spectral region used for imaging of the suspended API particles.
- Is ISPS spatially limited depending on the wavelength of laser used? And would you suggest the use of multivariate analysis over univariate analysis?
We use Raman microscope equipped with 532 nm laser light as the excitation source. The theoretical limit to spatial resolution is determined by diffraction. In practice, spatial resolution is determined by convolution of diffraction, dispersion, scattering, aberrations, motion, defocusing, etc.
Where, λ = wavelength of diffracted light
So based on Rayleigh criterion, spatial resolution for Raman images obtained with 532 nm excitation light and 100x magnification (NA=0.95) is ≈340 nm.
For univariate methods vibrational spectra can be evaluated by isolated absorption bands or signals. Univariate analysis is best used for strong Raman scatters that show high contrast at a specific wavelength in the imaging hypercube and there is no spectral interference from other ingredients in the spectral range used for imaging. Multivariate methods (e.g., Spectral Mixture Resolution and other chemometric tools ) are used to extract the information contained in larger spectral regions. Multivariate analysis is used for unknown components, polymorph ID or more complex mixtures.
- Is it possible to differentiate two grades of lactose in dry powder inhaler formulation? And also to quantify the grades?
We typically start with developing the spectral library for pure components and determine the feasibility to differentiate chemicals by their spectra by Raman spectroscopy and Raman Chemical Imaging. Based on spectral differences of the two lactose grades Raman chemical experimental parameters would be established to identify and quantify the grades in formulation. Development of a calibration model based on a chemometric multivariate procedures is typically required for quantitative analysis. For qualitative purposes only the spectra are used (usually in a PCA method), for quantitative purposes. Also the independently determined analytical reference data are taken into account (e.g. in PCR, PLS methods).
- Can we use this technique for PSD of API in a ground tablet containing 5-6 excipients?
Yes, Raman Chemical Imaging was shown to be very effective in determining API PSD in a ground tablet containing 5-6 excipients. Please refer to this application note available for downloading. Measuring Content Uniformity In Pharmaceutical Tablets Using Wide-Field Raman Chemical Imaging and Multivariate Image Processing. This note discusses analysis of an over-the-counter (OTC) pharmaceutical tablet which exhibits compositional heterogeneity between the active ingredient (aspirin) and the excipient matrix within the sample. The intact tablet appears homogeneous on a macro or microscopic scale when using conventional contrast enhancement since both the active and excipient materials are white powders and cannot be readily differentiated using optical microscopy.