AAPS PharmSci

, Volume 5, Issue 2, pp 39–47

Influence of solvents on the variety of crystalline forms of erythromycin

  • Sabiruddin Mirza
  • Inna Miroshnyk
  • Jyrki Heinämäki
  • Leena Christiansen
  • Milja Karjalainen
  • Jouko Yliruusi
Article

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 

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References

  1. 1.
    York P. Solid-state properties of powders in the formulation and processing of solid dosage forms. Int J Pharm. 1983;14:1–28.CrossRefGoogle Scholar
  2. 2.
    Marshal PV, York P. Crystallization solvent induced solid-state and particulate modifications of nitrofurantoin. Int J Pharm. 1989;55:257–263.CrossRefGoogle Scholar
  3. 3.
    Florence A, Attwood D. Physicochemical Principles of Pharmacy. 3rd ed. London, England: Macmillan Press Ltd. 1998:5–35.Google Scholar
  4. 4.
    Fukumori Y, Fukuda T, Yamamoto Y, et al. Physical characterization of erythromycin dihydrate, anhydrate and amorphous solid and their dissolution properties. Chem Pharm Bull. 1983;31:4029–4039.CrossRefGoogle Scholar
  5. 5.
    Bauer J, Quick J, Oheim R. Alternate interpretation of the role of water in the erythromycin structure. J Pharm Sci. 1985;74:899–900.CrossRefGoogle Scholar
  6. 6.
    Murthy KS, Turner NA, Nesbitt RU, Fawzi MB. Characterization of commercial lots of erythromycin base. Drug Dev Ind Pharm. 1986;12:665–690.CrossRefGoogle Scholar
  7. 7.
    Laine E, Kahela P, Rajala R, Heikkilä T, Saarnivaara K, Piippo I. Crystal forms and bioavailability of erythromycin. Int J Pharm. 1987;38:33–38.CrossRefGoogle Scholar
  8. 8.
    Stephenson GA, Stowell JG, Pascal HT, Pfeiffer RR, Byrn SR. Solid-state investigations of erythromycin A dihydrate: structure, NMR spectroscopy, and hygroscopicity. J Pharm Sci. 1997;86:1239–1244.PubMedCrossRefGoogle Scholar
  9. 9.
    Bauer JF, Dziki W, Quick JE. Role of an isomorphic desolvate in dissolution failures of an erythromycin tablet formulation. J Pharm Sci. 1999;88:1222–1227.PubMedCrossRefGoogle Scholar
  10. 10.
    Sarisuta N, Kumpugdee M, Müller BW, Puttipipatkhachorn S. Physico-chemical characterization of interactions between erythromycin and various film polymers. Int J Pharm. 1999;186:109–118.PubMedCrossRefGoogle Scholar
  11. 11.
    Kawakami K, Numa T, Ida Y. Assessment of amorphous content by microcalorimetry. J Pharm Sci. 2002;91:417–423.PubMedCrossRefGoogle Scholar
  12. 12.
    Kálmán A, Párkányi L. Isostructurality of organic compounds: a tool to estimate the complementarity of homo- and heteromolecular associates. In: Hargittai M, Hargittai I, eds. Advances in Molecular Structure Research. Vol. 3. Greenwich, CT: JAI Press; 1997:201–226.Google Scholar
  13. 13.
    Stephenson GA, Groleau EG, Kleemann RL, Xu W, Rigsbee DR. Formation of isomorphic desolvates: creating a molecular vacuum. J Pharm Sci. 1998;87:536–542.PubMedCrossRefGoogle Scholar
  14. 14.
    Morris KR. Structural aspects of hydrates and solvates. In: Brittain HG, ed. Polymorphism in Pharmaceutical Solids. New York, NY: Marcel Dekker; 1999:125–181.Google Scholar
  15. 15.
    Byrn SR, Pfeiffer RR, Stowell JG. A Solid State Chemistry of Drugs. New York, NY: Academic Press; 1999:279–303.Google Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2003

Authors and Affiliations

  • Sabiruddin Mirza
    • 1
  • Inna Miroshnyk
    • 1
  • Jyrki Heinämäki
    • 1
  • Leena Christiansen
    • 1
  • Milja Karjalainen
    • 1
  • Jouko Yliruusi
    • 1
    • 2
  1. 1.Pharmaceutical Technology Division, Department of PharmacyUniversity of HelsinkiFinland
  2. 2.Viikki Drug Discovery Technology CenterUniversity of HelsinkiFinland

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