Comparison of powder produced by evaporative precipitation into aqueous solution (EPAS) and spray freezing into liquid (SFL) technologies using novel Z-contrast STEM and complimentary techniques

Jason M. Vaughn, Xiaoxia Gao, Miguel Jose Yacaman, Keith P. Johnston, Robert O. Williams

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

The objective of this study was to compare the properties of particles formed by nucleation and polymer stabilization (e.g. evaporative precipitation into aqueous solution (EPAS)) versus rapid freezing (e.g. spray freezing into liquid (SFL)). Powders formed by EPAS and SFL, composed of danazol and PVP K-15 in a 1:1 ratio, were characterized using X-ray powder diffraction, modulated differential scanning calorimetry (MDSC), contact angle determination, dissolution, scanning electron microscopy (SEM), environmental scanning electron microscopy (ESEM), BET specific surface area, and Z-contrast scanning transmission electron microscopy (STEM). Large differences in particle morphologies and properties were observed and explained in terms of the particle formation mechanisms. Both techniques produced amorphous powders with high Tg and low contact angle values. However, STEM analysis showed highly porous bicontinuous nanostructured 30 nm particles connected by narrow bridges for SFL versus aggregated 500 nm primary particles for EPAS. The combination of STEM and other characterization techniques indicates solid solutions were formed for the SFL powders consistent with rapid freezing. In contrast, the EPAS particle cores are enriched in hydrophobic API and the outer surface is enriched in the hydrophilic polymer, with less miscibility than in the SFL powders. Consequently, dissolution rates are faster for the SFL particles, although both techniques enhanced dissolution rates of the API.

Original languageEnglish (US)
Pages (from-to)81-89
Number of pages9
JournalEuropean Journal of Pharmaceutics and Biopharmaceutics
Volume60
Issue number1
DOIs
StatePublished - May 2005
Externally publishedYes

Keywords

  • Freezing
  • Particle engineering processes
  • Precipitation

ASJC Scopus subject areas

  • Biotechnology
  • Pharmaceutical Science

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