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Isothermal Crystallization of Imwitor 742 from Supercooled Liquid State

Pharmaceutical Research volume 24, pages 738–747 (2007)Cite this article

Purpose

Crystallization behavior of Imwitor 742 was investigated for use as a liquid-filled capsule carrier.

Materials and Methods

The crystallization behavior of Imwitor 742 was assessed using DSC, X-ray diffraction, and microscopy. The physical stability of Imwitor 742 under refrigerated and ambient conditions was estimated by isothermal crystallization studies using DSC. The effect of hard capsule shells and additives on crystallization kinetics was also examined.

Results

When Imwitor 742 was cooled in the DSC measurement, the form α appeared at −20°C. When this form was heated from −40°C, melt-crystallization into the form β + β′ was initiated at −30°C, followed by successive melting. Isothermal crystallization studies at temperatures higher than −14°C yielded the form β + β′. The crystallization behavior was explained in terms of the Avrami model fitting by assuming 2-dimensional crystal growth. Kinetic analysis suggested that the liquid state of Imwitor 742 was maintained for 46 h and 40 months at 5 and 25°C, respectively, although the deviation in induction time was expected to be large at these temperatures. Addition of hard capsule shells promoted the crystallization behavior, while addition of drug or water prolonged the induction time.

Conclusion

The supercooled liquid state of Imwitor 742 was quite stable. However, additives to retard crystallization should be used, because the deviation in the induction time was very large. Hard capsule shells enhanced the crystallization of Imwitor 742, possibly by acting as nuclei for crystal growth.

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Author notes

  1. Kohsaku Kawakami

    Present address: Biomaterials Center, National Institute for Materials Science, 1-1, Namiki, Tsukuba, Ibaraki, 305-0044, Japan

Affiliations

  1. PreClinical Development, Banyu Tsukuba Research Institute, 3 Okubo, Tsukuba, Ibaraki, 300-2611, Japan

    Kohsaku Kawakami

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  1. Kohsaku Kawakami
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Correspondence to Kohsaku Kawakami.

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Kawakami, K. Isothermal Crystallization of Imwitor 742 from Supercooled Liquid State. Pharm Res 24, 738–747 (2007). https://doi.org/10.1007/s11095-006-9193-0

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  • DOI: https://doi.org/10.1007/s11095-006-9193-0

Key words

  • crystallization
  • DSC
  • Imwitor 742
  • induction time
  • liquid-filled capsules