The Particle Articles

In our latest webinar on Thursday, Aug. 23rd, Gateway Analytical's Senior Scientist Oksana Olkhovyk presented a webinar designed for scientists working in the area of polymorph evaluation in pharmaceutical products and discussed the benefits of using Raman microscopy and chemical imaging for in vitro characterization of polymorphs.

During the webinar Q & A session, the audience presented a number of questions to Oksana. You can find the questions and answers below. Also, you can find quick links to where you can replay the webinar or download the presentation slides.

Webinar Replay: Polymorph Analysis Using Raman Chemical Imaging
Presentation Slides: Polymorph Analysis Using Raman Chemical Imaging

1. Can Raman Chemical Imaging (RCI) be used to study polymorphic changes in-situ in pressurized MDI products, assuming the pressurized container is clear and the solid API is dispersed in an HFA propellant?
   RCI was shown to be extremely beneficial for MDI and DPI formulations. You can find some useful resources available via this link for further information:
   • Ingredient-Specific Particle Sizing of Combivent® Presented at: RDD 2010
   • Metered-Dose Inhaler
   • Multivariate analysis of hyperspectral Raman Chemical Images for drug-specific particles sizing of combination inhalation aerosol, presented at: AAPS 2010
   • Available via following link: http://www.chemimage.com/resources/posters/pharmaceutical.aspx
2. Is it possible to quantify the mix of polymorph? How?
   Yes, by utilizing calibration and Chemometric techniques discussed in slides 14-24 of the webinar.
3. As a part of your Ingredient-Specific Particle Sizing, do you also perform work on transdermals?
   Yes, we do work with semisolids (creams, gels, ointments) and transdermal delivery systems. You can find more information, you can refer to the “Evaluating API Heterogeneity in a Multilayered Transdermal Patch” application note.
4. RCI Vs XRPD? What are the pros and cons for polymorph detection in composition?
   • X-Ray Diffraction is incapable of being applied in-situ to understand phase transition mechanisms that define polymorph-dependent nucleation, crucial for manufacturing and stabilizing chemical compounds.
   • Raman Spectroscopy and Imaging can be applied in-situ to understand nucleation processes that manifest metastable or amorphous forms that may not be easily isolated for x-ray diffraction analysis and to investigate phase transitions due to unwanted impurities, effect of external parameters: temperature, pressure, melt-mediation, solution-mediation.
   • Widefield Raman Chemical Imaging provides means to rapidly scan whole sample area with drastically improved sampling statistics and provides results that are less sensitive to crystal orientation and human interpretation bias as a result of automated spectral analysis capabilities.
5. Which brand and model of the Raman do you use and recommend?
   For Raman Chemical Imaging application we utilize a ChemImage Falcon II Raman Chemical Imaging System and Bruker Senterra Raman System. You can refer to our Instrumentation and Techniques section on our website listing other techniques we utilize:
   • Fluorescence Microscopy
   • FT-IR Spectroscopy
   • Optical Microscopy
   • Polarized Light Microscopy
   • Raman Spectroscopy
   • Raman, Visible, Fluorescence and Near Infrared (NIR) Chemical Imaging
   • Scanning Electron Microscopy / Energy Dispersive Spectroscopy (SEM/EDS)
   • Specialized Sample Preparation
6. How can we use RCI for studying protein stability?
   A feasibility study should be performed to determined applicability of RCI for studying specific protein stability applications.
7. What is the relationship between the DSC glass transition energy and the RCI of the polymorphs?
   • The answer to this question may be found in the poster on Polymorphic Discrimination during Crystallization from a Room Temperature Acetaminophen Glass using Raman Chemical Imaging
   • Or by reviewing following resource Investigation of Polymorphic Transformations Using Raman Chemical Imaging & Differential Scanning Calorimetry
8. How do you measure 96 well plates, and if so which plates are recommended for organic solvents?
   The samples can be prepared by mixing exemplary excipients/solvents and exemplary APIs at specified percentages (wt/wt) to fill the 96 well plate which is suitable for use with organic solvents and does not interfere with the Raman signal from analyte. A 96 well plate can be analyzed on Raman imaging system to obtain Bright Field Reflection Image, Raman Spectrum and Raman Chemical Image at each well for which XYZ list coordinates are determined in an automated fashion using automated acquisition operating with established experimental parameters for each modality: Bright Field Reflection Image, Raman Spectrum and Raman Chemical Image.