Frozen and Freeze Dried Systems

Two glass ampoules on a frosty blue surface.

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. 

Further Reading

  1. P. Sundaramurthi, R. Suryanarayanan. Calorimetry and complementary techniques to characterize frozen and freeze-dried systems. Adv Drug Deliv Rev, 64(5), 384-395 (2012).
  2. R.K. Cavatur, R. Suryanarayanan. Characterization of phase transitions during freeze-drying by in situ X-ray powder diffractometry. Pharm Dev Technol, 3(4), 579-586 (1998).
  3. P. Sundaramurthi, R. Suryanarayanan. Trehalose crystallization during freeze-drying: Implications on lyoprotection. J Phys Chem Lett, 1(2), 510-514 (2010).
  4. P. Sundaramurthi, E. Shalaev, R. Suryanarayanan. “pH Swing” In Frozen Solutions - Consequence of Sequential Crystallization of Buffer Components. J Phys Chem Lett, 1(1), 265-268 (2010).
  5. A.A. Thorat, B. Munjal, T.W. Geders, R. Suryanarayanan. Freezing-induced protein aggregation-Role of pH shift and potential mitigation strategies. J Control Release, 323, 591-599 (2020).
  6. S. Thakral, J. Sonje, R. Suryanarayanan. Anomalous behavior of mannitol hemihydrate: Implications on sucrose crystallization in colyophilized systems. Int J Pharm, 587, 119629 (2020).
  7. B.S. Bhatnagar, J. Sonje, E. Shalaev, S.W.H. Martin, D.L. Teagarden, R. Suryanarayanan. A refined phase diagram of the tert-butanol–water system and implications on lyophilization process optimization of pharmaceuticals. Phys Chem Chem Phys, 22(3), 1583-1590 (2020).