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Origin of Two Modes of Non-isothermal Crystallization of Glasses Produced by Milling

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ABSTRACT

Purpose

To mechanistically explain the origin of two distinct non-isothermal crystallization modes, single-peak (unimodal) and two-peak (bimodal), of organic glasses.

Methods

Glasses of ten organic molecules were prepared by melt-quenching and cryogenic milling of crystals. Non-isothermal crystallization of glasses was monitored using differential scanning calorimetry and powder X-ray diffractometry.

Results

The non-isothermal crystallization of glass, generated by milling, is either unimodal or bimodal, while that of melt-quenched glass without being milled is always unimodal. The mode of crystallization of amorphous phase depends on the relative position of the crystallization onset (T c ) with respect to glass transition temperature (T g ), and can be explained by a surface crystallization model. Bimodal crystallization event is observed when T c is below or near T g , due to the fast crystallization onset at milled glass surfaces. Unimodal crystallization is observed when T c is well above T g . We have verified this model by intentionally inducing flip between the two crystallization modes for several compounds through manipulating glass surface area and T c .

Conclusions

The two modes of crystallization of organic glasses is a result of the combined effects of faster surface crystallization and variation in specific surface area by milling.

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Acknowledgments & DISCLOSURES

We thank Boehringer-Ingelheim Pharmaceuticals Inc, Ridgefield, CT for financial support to this work. Some of the experiments were performed at the University of Minnesota I.T. Characterization Facility, which receives partial support from the NSF through the NNIN program.

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Authors and Affiliations

  1. Pharmaceutical Materials Science & Engineering Laboratory Department of Pharmaceutics, University of Minnesota, 9-127B Weaver-Densford Hall, 308 Harvard Street S.E., Minneapolis, Minneapolis, 55455, USA

    Sayantan Chattoraj & Changquan Calvin Sun

  2. Pharmaceutical Development Boehringer-Ingelheim Pharmaceuticals Inc., Ridgefield, Connecticut, USA

    Chandan Bhugra, Chitra Telang, Li Zhong & Zeren Wang

Authors
  1. Sayantan Chattoraj
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  2. Chandan Bhugra
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  3. Chitra Telang
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  4. Li Zhong
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  5. Zeren Wang
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  6. Changquan Calvin Sun
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Corresponding author

Correspondence to Changquan Calvin Sun.

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Chattoraj, S., Bhugra, C., Telang, C. et al. Origin of Two Modes of Non-isothermal Crystallization of Glasses Produced by Milling. Pharm Res 29, 1020–1032 (2012). https://doi.org/10.1007/s11095-011-0644-x

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  • DOI: https://doi.org/10.1007/s11095-011-0644-x

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