Nucleation is the first step of crystallization of glasses. However, the difficulty in detecting the nuclei makes control of the crystallization behavior of the glasses difficult. This chapter discusses how nucleation of pharmaceutical glass affects its glass properties and performances including storage stability and dissolution behavior. The investigation was made for celecoxib, a poorly soluble drug to treat osteoarthritis, rheumatoid arthritis, acute pain, and so on, as a model compound. The nuclei were formed by deep cooling and its influence was assessed by comparing its properties with those of fresh glass. Their relaxation behavior was evaluated using differential scanning calorimetry (DSC) and broadband dielectric spectroscopy (BDS). Change in size of cooperatively rearranging region (CRR) was also discussed. Negative impact of the nucleation was found for the storage stability at 35 °C; however, no influence of nuclei was found at the higher temperature storage because of appearance of a different crystal form. Nucleated glass exhibited poorer dissolution performance relative to non-nucleated one, suggesting that crystallization was accelerated after suspension of the glass in the aqueous media. These results should enable more precise control of performances of the pharmaceutical glasses.

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Nuclei Formation in Pharmaceutical Glasses

  • Kohsaku Kawakami

摘要

Nucleation is the first step of crystallization of glasses. However, the difficulty in detecting the nuclei makes control of the crystallization behavior of the glasses difficult. This chapter discusses how nucleation of pharmaceutical glass affects its glass properties and performances including storage stability and dissolution behavior. The investigation was made for celecoxib, a poorly soluble drug to treat osteoarthritis, rheumatoid arthritis, acute pain, and so on, as a model compound. The nuclei were formed by deep cooling and its influence was assessed by comparing its properties with those of fresh glass. Their relaxation behavior was evaluated using differential scanning calorimetry (DSC) and broadband dielectric spectroscopy (BDS). Change in size of cooperatively rearranging region (CRR) was also discussed. Negative impact of the nucleation was found for the storage stability at 35 °C; however, no influence of nuclei was found at the higher temperature storage because of appearance of a different crystal form. Nucleated glass exhibited poorer dissolution performance relative to non-nucleated one, suggesting that crystallization was accelerated after suspension of the glass in the aqueous media. These results should enable more precise control of performances of the pharmaceutical glasses.