Detection and characterization of trace crystallinity within amorphous

pharmaceutical formulations using second harmonic generation imaging

We would like to congratulate our own Dr. Ellen Gualtieri, PhD on her selection to present her research on second harmonic generation in determining crystallinity in amorphous pharmaceutical formulations at the upcoming Gordon Research Conference on Bioanalytical Sensors!

 

The conference titled, "State-of-the-Art Bioanalytical Sensing Approaches for Healthcare and Therapeutics, Forensics, and Visualization of Living Systems" will be held June 24 - 29, 2018 at Salve Regina University in Newport, RI.

 

Dr. Gualtieri's talk will be held June 25th at 10:30 am (abstract below).

 

Detection and characterization of trace crystallinity within amorphous pharmaceutical formulations using second harmonic generation imaging

The number of drug candidates with poor solubility (according to the Biopharmaceutical Classification System) has been steadily rising in the past years. One of the prevailing technologies to address this problem is the formulation of Amorphous Solid Dispersions (ASDs), in which an Active Pharmaceutical Ingredient (API) is stabilized in its amorphous form by dispersion in polymers. Spray dry methods are among the most popular used to generate amorphous dispersions of the drug with the goal to have little-to-no crystalline API in the matrix. Any presence of crystalline material can directly impact bioavailability and hence efficacy and dosage of the final drug. Powder X-ray diffraction is the gold standard in quantifying crystalline material in amorphous formulations but can only detect 1% crystalline material. Many drug formulations have only a few percent or less of API meaning that 100% of the API in the drug product would have to be crystalline in order to be detected by standard detects. This directly impacts quality control and efficacy of drugs going to market. Second Order Nonlinear  Optical Imaging (SONICC) has recently been demonstrated as a sensitive, non-destructive, high throughput technique for detecting crystallinity in ASDs down to 0.001%.1-7 At the GRC, Ellen Gualtieri will present how SONICC can be used for routine screening of ppm crystallinity within ASDs as well as kinetic modeling through accelerated stability testing.

 

Parts per million crystallinity detection with SONICC

 

References

  1. Song Z, Sarkar S, Vogt AD, Danzer Gd, Smith CJ, Gualtieri EJ, Simpson GJ,”Kinetic modeling of accelerated stability testing enabled by second harmonic generation microscopy.” Anal Chem  2018, 90(7):4406-441.
  2. Correa-Soto C, Trasi NS, Schmitt PD, Su Y, Liu Z, Miller E, Variankaval N, Marsac PJ, Simpson GJ, Taylor LS. “Second harmonic generation microscopy as a tool for the early detection of crystallization in spray dried dispersions”; J Pharm Biomed Anal. 2017, 146:86-95.
  3. Wanapun, D.; Kestur, U. S.; Kissick, D. J.; Simpson, G. J.; Taylor, L. S., Selective Detection and Quantitation of Organic Molecule Crystallization by Second Harmonic Generation Microscopy. Anal Chem 2010, 82 (13), 5425-5432.
  4. Toth, S. J.; Madden, J. T.; Taylor, L. S.; Marsac, P.; Simpson, G. J., Selective Imaging of Active Pharmaceutical Ingredients in Powdered Blends with Common Excipients Utilizing Two-Photon Excited Ultraviolet-Fluorescence and Ultraviolet-Second Order Nonlinear Optical Imaging of Chiral Crystals. Anal Chem 2012, 84 (14), 5869-5875.
  5. Schmitt, P. D.; Trasi, N. S.; Taylor, L. S.; Simpson, G. J., Finding the Needle in the Haystack: Characterization of Trace Crystallinity in a Commercial Formulation of Paclitaxel Protein-Bound Particles by Raman Spectroscopy Enabled by Second Harmonic Generation Microscopy. Mol Pharmaceut 2015, 12 (7), 2378-2383.
  6. Chowdhury, A. U.; Zhang, S. J.; Simpson, G. J., Powders Analysis by Second Harmonic Generation Microscopy. Anal Chem 2016, 88 (7), 3853-3863.
  7. Chowdhury, A. U.; Ye, D. H.; Song, Z. T.; Zhang, S. J.; Hedderich, H. G.; Mallick, B.; Thirunahari, S.; Ramakrishnan, S.; Sengupta, A.; Gualtieri, E. J.; Bouman, C. A.; Simpson, G. J., Second Harmonic Generation Guided Raman Spectroscopy for Sensitive Detection of Polymorph Transitions. Anal Chem 2017, 89 (11), 5959-5966.