Pharmaceutical Research

, Volume 27, Issue 8, pp 1558–1567 | Cite as

Fast Surface Crystallization of Amorphous Griseofulvin Below T g

Research Paper

ABSTRACT

Purpose

To study crystal growth rates of amorphous griseofulvin (GSF) below its glass transition temperature (T g) and the effect of surface crystallization on the overall crystallization kinetics of amorphous GSF.

Methods

Amorphous GSF was generated by melt quenching. Surface and bulk crystal growth rates were determined using polarized light microscope. X-ray powder diffraction (XRPD) and Raman microscopy were used to identify the polymorph of the crystals. Crystallization kinetics of amorphous GSF powder stored at 40°C (T g−48°C) and room temperature (T g−66°C) was monitored using XRPD.

Results

Crystal growth at the surface of amorphous GSF is 10- to 100-fold faster than that in the bulk. The surface crystal growth can be suppressed by an ultrathin gold coating. Below T g, the crystallization of amorphous GSF powder was biphasic with a rapid initial crystallization stage dominated by the surface crystallization and a slow or suspended late stage controlled by the bulk crystallization.

Conclusions

GSF exhibits the fastest surface crystallization kinetics among the known amorphous pharmaceutical solids. Well below T g, surface crystallization dominated the overall crystallization kinetics of amorphous GSF powder. Thus, surface crystallization should be distinguished from bulk crystallization in studying, modeling and controlling the crystallization of amorphous solids.

KEY WORDS

amorphous solids coating crystallization kinetic griseofulvin surface-enhanced crystallization 

Notes

ACKNOWLEDGEMENTS

The work is supported by Amgen summer internship program. We thank Dr.Yuan-hon Kiang, Dr. Darren Reid in Amgen and Professor Lian Yu in University of Wisconsin—Madison for helpful discussions and valuable comments.

REFERENCES

  1. 1.
    Yu L. Amorphous pharmaceutical solids: preparation, characterization and stabilization. Adv Drug Deliv Rev. 2001;48:27–42.CrossRefPubMedGoogle Scholar
  2. 2.
    Kennedy M, Hu J, Gao P, Li L, Ali-Reynolds A, Chal B, et al. Enhanced bioavailability of a poorly soluble VR1 antagonist using an amorphous solid dispersion approach: a case study. Mol Pharm. 2008;5:981–93.CrossRefPubMedGoogle Scholar
  3. 3.
    Abu TMS. Solid dispersion of poorly water-soluble drugs: Early promises, subsequent problems, and recent breakthroughs. J Pharm Sci. 1999;88:1058–66.CrossRefGoogle Scholar
  4. 4.
    Guo Y, Byrn SR, Zografi G. Physical characteristics and chemical degradation of amorphous quinapril hydrochloride. J Pharm Sci. 2000;89:128–43.CrossRefPubMedGoogle Scholar
  5. 5.
    Ediger MD, Harrowell P, Yu L. Crystal growth kinetics exhibit a fragility-dependent decoupling from viscosity. J Chem Phys. 2008;128:034709/1–6.CrossRefGoogle Scholar
  6. 6.
    Hancock BC, Shamblin SL, Zografi G. Molecular mobility of amorphous pharmaceutical solids below their glass transition temperatures. Pharm Res. 1995;12:799–806.CrossRefPubMedGoogle Scholar
  7. 7.
    Hancock BC, Zograti G. Characteristics and significance of the amorphous state in pharmaceutical systems. J Pharm Sci. 1997;86:1–12.CrossRefPubMedGoogle Scholar
  8. 8.
    Tombari E, Presto S, Johari G, Shanker R. Molecular mobility, thermodynamics and stability of Griseofulvin’s ultraviscous and glassy states from dynamic heat capacity. Pharm Res. 2008;25:902–12.CrossRefPubMedGoogle Scholar
  9. 9.
    Zhou D, Geoff G, Law D, Grant DJW, Schmitt EA. Thermodynamics, molecular mobility and crystallization kinetics of amorphous griseofulvin. Mol Pharm. 2008;5:927–36.CrossRefPubMedGoogle Scholar
  10. 10.
    Wu T, Yu L. Surface crystallization of indomethacin below Tg. Pharm Res. 2006;23:2350–5. Epub 2006 Aug 2323.CrossRefPubMedGoogle Scholar
  11. 11.
    Zhu L, Wong L, Yu L. Surface-enhanced crystallization of amorphous nifedipine. Mol Pharm. 2008;5:921–6.CrossRefPubMedGoogle Scholar
  12. 12.
    Yamamura S, Takahira R, Momose Y. Crystallization kinetics of amorphous griseofulvin by pattern fitting procedure using X-ray diffraction data. Pharm Res. 2007;24:880–7.CrossRefPubMedGoogle Scholar
  13. 13.
    Wu T, Yu L. Origin of enhanced crystal growth kinetics near Tg probed with indomethacin polymorphs. J Phys Chem B Condens Matter Mater Surf Interfaces Biophys. 2006;110:15694–9.PubMedGoogle Scholar
  14. 14.
    Matsumo T, Bogue DC. Stress birefringence in amorphous polymers under nonisothermal conditions. J Polym Sci Polym Phys Ed. 1977;15:1663–74.CrossRefGoogle Scholar
  15. 15.
    Wu T, de Villiers M, Yu L. Inhibiting surface crystallization of amorphous indomethacin by nanocoating. Langmuir. 2007;23:5148–53.CrossRefPubMedGoogle Scholar
  16. 16.
    Ishida H, Wu T, Yu L. Sudden rise of crystal growth rate of nifedipine near T g without and with polyvinylpyrrolidone. J Pharm Sci. 2007;96:1131–8.CrossRefPubMedGoogle Scholar
  17. 17.
    Yu L, Reutzel-Edens SM, Mitchell CA. Crystallization and polymorphism of conformationally flexible molecules: problems, patterns, and strategies. Org Process Res Dev. 2000;4:396–402.CrossRefGoogle Scholar
  18. 18.
    Swallen S, Kearns K, Mapes M, Kim Y, McMahon R, Ediger M, et al. Organic glasses with exceptional thermodynamic and kinetic stability. Science. 2007;315:353–6.Google Scholar
  19. 19.
    Fakhraai Z, Forrest JA. Measuring the surface dynamics of glassy polymers. Science. 2008;319:600–4.CrossRefPubMedGoogle Scholar
  20. 20.
    Sun Y, Xi H, Chen S, Ediger MD, Yu L. Crystallization near glass transition: transition from diffusion-controlled to diffusionless crystal growth studied with seven polymorphs. J Phys Chem B. 2008;112:5594–601.CrossRefPubMedGoogle Scholar
  21. 21.
    Sun Y, Xi H, Ediger MD, Richert R, Yu L. Diffusion-controlled and “diffusionless” crystal growth near the glass transition temperature: relation between liquid dynamics and growth kinetics of seven ROY polymorphs. J Chem Phys. 2009;131:074506–9.CrossRefPubMedGoogle Scholar
  22. 22.
    Xi H, Sun Y, Yu L. Diffusion-controlled and diffusionless crystal growth in liquid o-terphenyl near its glass transition temperature. J Chem Phys. 2009;130:094508–9.CrossRefPubMedGoogle Scholar
  23. 23.
    Savolainen M, Heinz A, Strachan C, Gordon KC, Yliruusi J, Rades T, Sandler N. Screening for differences in the amorphous state of indomethacin using multivariate visualization. Eur J Pharm Sci. 2007;30:113–23.CrossRefPubMedGoogle Scholar
  24. 24.
    Luo D, Anderson BD. Application of a two-state kinetic model to the heterogeneous kinetics of reaction between cysteine and hydrogen peroxide in amorphous lyophiles. J Pharm Sci. 2008;97:3907–26.CrossRefPubMedGoogle Scholar
  25. 25.
    Dawson KJ, Kearns KL, Ediger MD, Sacchetti MJ, Zografi GD. Highly stable indomethacin glasses resist uptake of water vapor. J Phys Chem B. 2009;113:2422–7.CrossRefPubMedGoogle Scholar
  26. 26.
    Forster A, Hempenstall J, Tucker I, Rades T. The potential of small-scale fusion experiments and the Gordon–Taylor equation to predict the suitability of drug/polymer blends for melt extrusion. Drug Dev Ind Pharm. 2001;27:549–60.CrossRefPubMedGoogle Scholar
  27. 27.
    Yoshioka M, Hancock BC, Zografi G. Crystallization of indomethacin from the amorphous state below and above its glass transition temperature. J Pharm Sci. 1994;83:1700–5.CrossRefPubMedGoogle Scholar
  28. 28.
    Bhugra C, Shmeis R, Krill S, Pikal M. Predictions of onset of crystallization from experimental relaxation times I-correlation of molecular mobility from temperatures above the glass transition to temperatures below the glass transition. Pharm Res. 2006;23:2277–90.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Department of ChemistryUniversity of Wisconsin—MadisonMadisonUSA
  2. 2.Small Molecule Process and Product DevelopmentAmgen Inc.Thousand OaksUSA

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