Frozen & Freeze Dried Systems

glass tinctures on top of ice

We characterize the behavior of excipients in frozen and freeze-dried systems with the goal of identifying the challenges associated with the use of excipients in multicomponent lyophilized formulations. Specifically, we are involved in determining the impact of formulation and processing variables on the phase behavior of excipients and their functionalities.  We use multiple analytical techniques including sub-ambient differential scanning calorimetry, low temperature X-ray diffractometry (both laboratory and synchrotron) and low temperature pH measurement. A recent addition is low temperature small angle neutron scattering. Our studies are also aimed at characterizing the phase behavior of the formulation components so as to develop optimum lyophilization cycles. 

Representative publications

  1. Sundaramurthi, Prakash, and Raj Suryanarayanan. "Calorimetry and complementary techniques to characterize frozen and freeze-dried systems." Advanced Drug Delivery Reviews 64.5 (2012): 384-395.
  2. R.K. Cavatur and R. Suryanarayanan, "Characterization of phase transitions during freeze-drying by in situ X-ray powder diffractometry." Pharmaceutical Development and Technology 3.4 (1998): 579–586.
  3. Sundaramurthi, Prakash, and Raj Suryanarayanan. "Trehalose crystallization during freeze-drying: Implications on lyoprotection." The Journal of Physical Chemistry Letters 1.2 (2010): 510-514.
  4. Sundaramurthi, Prakash, Evgenyi Shalaev, and Raj Suryanarayanan. "“pH Swing” In Frozen Solutions - Consequence of Sequential Crystallization of Buffer Components." The Journal of Physical Chemistry Letters 1.1 (2010): 265-268.
  5. Thorat, Alpana A., et al. "Freezing-induced protein aggregation-Role of pH shift and potential mitigation strategies." Journal of Controlled Release 323 (2020): 591-599.
  6. Thakral, Seema, Jayesh Sonje, and Raj Suryanarayanan. "Anomalous behavior of mannitol hemihydrate: Implications on sucrose crystallization in colyophilized systems." International Journal of Pharmaceutics 587 (2020): 119629.
  7. Bhatnagar, Bakul S., et al. "A refined phase diagram of the tert-butanol–water system and implications on lyophilization process optimization of pharmaceuticals." Physical Chemistry Chemical Physics 22.3 (2020): 1583-1590.