AAPS PharmSci

, Volume 5, Issue 2, pp 39–47

Influence of solvents on the variety of crystalline forms of erythromycin

Authors

    • Pharmaceutical Technology Division, Department of PharmacyUniversity of Helsinki
  • Inna Miroshnyk
    • Pharmaceutical Technology Division, Department of PharmacyUniversity of Helsinki
  • Jyrki Heinämäki
    • Pharmaceutical Technology Division, Department of PharmacyUniversity of Helsinki
  • Leena Christiansen
    • Pharmaceutical Technology Division, Department of PharmacyUniversity of Helsinki
  • Milja Karjalainen
    • Pharmaceutical Technology Division, Department of PharmacyUniversity of Helsinki
  • Jouko Yliruusi
    • Pharmaceutical Technology Division, Department of PharmacyUniversity of Helsinki
    • Viikki Drug Discovery Technology CenterUniversity of Helsinki
Article

DOI: 10.1208/ps050212

Cite this article as:
Mirza, S., Miroshnyk, I., Heinämäki, J. et al. AAPS PharmSci (2003) 5: 39. doi:10.1208/ps050212

Abstract

The influence of the organic solvents widely used in the pharmaceutical industry (acetone, methylethylketone, ethanol, and isopropanol) both in the presence and in the absence of water on the crystallization behavior of erythromycin (Em), a clinically relevant antibiotic of the macrolide group, was investigated. It was observed that despite a high preference for water as a guest molecule, Em rather easily forms solvates with the organic solvents studied. Consequently, 4 distinct solvates of Em have been isolated by recrystallization: acetonate, methylethylketonate, ethanolate, and isopropanolate. It was established that in a pure organic solvent, or 1∶9 or 1∶1 water-organic solvent mixtures, the corresponding solvate is always crystallized. However, the recrystallization of erythromycin from 2∶1 water-organic solvent (excluding methylethylketone) mixture results in the formation of a crystal hydrate form. X-ray powder diffraction revealed the isostructurality of the solvates with acetone and methylethylketone. Thermogravimetric analysis showed that the loss of volatiles by all of the solvated crystals is nonstoichiometric. The desolvation behavior of the solvates with the organic solvents studied by means of variable-temperature x-ray powder diffraction indicates that in contrast to erythromycin dihydrate, they belong to a different class of solvates—those that produce an amorphous material upon desolvation.

Keywords

erythromycin crystallization solvated crystals isostructurality clathrate x-ray diffraction

Copyright information

© American Association of Pharmaceutical Scientists 2003