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The Effect of Temperature on Hydrogen Bonding in Crystalline and Amorphous Phases in Dihydropyrine Calcium Channel Blockers

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Abstract

Purpose: To investigate the effect of temperature on hydrogen bonding in a series of structurally related amorphous and crystalline compounds to gain a better molecular-level understanding of structural differences in the various phases.

Methods: FT-infrared spectra of seven 1,4-dihydropyridine calcium channel blockers were obtained at temperatures between 0 and 200°C using a temperature-controlled attenuated total reflection accessory. Thermal behavior was characterized using differential scanning calorimetry.

Results: Hydrogen bonding was investigated by monitoring the position of the NH stretching vibration, where an increase in peak wavenumber was taken to indicate a weakening of hydrogen bonding. Heating resulted in a reduction in hydrogen bonding strength, which was greatest for liquids and less for glassy and crystalline phases. For the amorphous samples, a plot of NH peak position vs. temperature displayed a discontinuity in the region of the glass transition (determined using differential scanning calorimetry) indicating that hydrogen bonding weakened abruptly as the material passed through the glass transition. This effect was more pronounced for some samples than for others.

Conclusions: The variation in the decrease in hydrogen-bonding interactions with increasing temperature for the different phases is consistent with greater configurational freedom as one moves from crystal to glass to liquid.

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Authors and Affiliations

  1. School of Pharmacy, U-2092, University of Connecticut, 372 Fairfield Road, Storrs, Connecticut, 06269-2092

    Xiaolin Charlie Tang & Michael J. Pikal

  2. Solid State Analysis, Pharmaceutical and Analytical R&D, AstraZeneca R&D Mölndal, S-431 83, Mölndal, Sweden

    Lynne S. Taylor

Authors
  1. Xiaolin Charlie Tang
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  2. Michael J. Pikal
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  3. Lynne S. Taylor
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Correspondence to Lynne S. Taylor.

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Tang, X.C., Pikal, M.J. & Taylor, L.S. The Effect of Temperature on Hydrogen Bonding in Crystalline and Amorphous Phases in Dihydropyrine Calcium Channel Blockers. Pharm Res 19, 484–490 (2002). https://doi.org/10.1023/A:1015199713635

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