Freeze crystallization of imipenem

Michael Connolly, Pablo G. Debenedetti, Hsien Hsin Tung

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


This work is a study of the freeze crystallization process developed for the production of a rapidly soluble and stable crystalline form of imipenem, an antibiotic. The objective is to understand the relationship between process conditions and the product crystallinity during the freeze crystallization. Solutions of imipenem and sodium bicarbonate, a drug stabilizer, were crystallized in acetone-water solvent systems at various ratios and temperatures. The degree of crystallinity of the resulting products was measured using an X-ray powder diffraction analysis technique. The acetone-water S-L phase diagram was used to correlate the resulting degrees of crystallinity of imipenem products and equilibrium properties of the system. It was discovered that the conversion of amorphous imipenem to crystalline products was directly related to the percentage of equilibrium liquid during the freeze crystallization. Solubility data indicated that imipenem is virtually insoluble in these equilibrium liquid phases. This suggests that the phase transition from the amorphous state to the crystalline state is mediated by the presence of a liquid phase.

Original languageEnglish (US)
Pages (from-to)174-177
Number of pages4
JournalJournal of Pharmaceutical Sciences
Issue number2
StatePublished - Feb 1996

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science


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