Pharmaceutical Research

, Volume 23, Issue 10, pp 2368–2374

Solute Crystallization in Frozen Systems–Use of Synchrotron Radiation to Improve Sensitivity

  • Dushyant B. Varshney
  • Satyendra Kumar
  • Evgenyi Y. Shalaev
  • Shin-Woong Kang
  • Larry A. Gatlin
  • Raj Suryanarayanan
Research Paper

DOI: 10.1007/s11095-006-9051-0

Cite this article as:
Varshney, D.B., Kumar, S., Shalaev, E.Y. et al. Pharm Res (2006) 23: 2368. doi:10.1007/s11095-006-9051-0

Abstract

Purpose

To demonstrate the sensitivity of low temperature synchrotron X-ray diffractometry (SXRD) for detecting solute crystallization in frozen sodium phosphate buffer solutions. To determine the effect of annealing on solute crystallization in frozen solutions.

Materials and Methods

Sodium phosphate buffer solutions, at initial buffer concentrations ranging from 1 to 100 mM (pH 7.4) were cooled to −50°C. The crystallization of disodium hydrogen phosphate dodecahydrate (Na2HPO4 •12H2O) was monitored using a laboratory as well as a synchrotron source. At selected concentrations, the effect of annealing (at −20°C) was investigated.

Results

With the laboratory source, solute crystallization, based on the appearance of one diagnostic peak with a d-spacing of 5.4 Å, was evident only when the initial buffer concentration was at least 50 mM. In contrast, using SXRD, crystallization was detected at initial buffer concentrations down to 1 mM. In addition, the use of a high-resolution 2D detector enabled the visualization of numerous diffraction rings of the crystalline solute. At both 10 and 100 mM buffer concentration, there was no increase in solute crystallization due to annealing.

Conclusion

By using synchrotron radiation, solute crystallization was detected with substantially increased sensitivity, making the technique useful for freeze-drying cycles of practical and commercial importance. Since numerous peaks of the crystalline solute appeared, the technique has potential utility in complex, multi-component systems.

Key words

annealingbuffer saltdisodium hydrogen phosphate dodecahydratesolute crystallizationsynchrotron XRD

Copyright information

© Springer Science + Business Media, Inc. 2006

Authors and Affiliations

  • Dushyant B. Varshney
    • 1
    • 2
  • Satyendra Kumar
    • 3
  • Evgenyi Y. Shalaev
    • 4
  • Shin-Woong Kang
    • 3
  • Larry A. Gatlin
    • 4
  • Raj Suryanarayanan
    • 1
  1. 1.Department of Pharmaceutics, College of PharmacyUniversity of MinnesotaMinneapolisUSA
  2. 2.Eli Lilly and CompanyLilly Corporate CenterIndianapolisUSA
  3. 3.Department of PhysicsKent State UniversityKentUSA
  4. 4.Pfizer Groton LaboratoriesGrotonUSA