Dehydration Kinetics of Pharmaceutical Hydrate: Effects of Environmental Conditions and Crystal Forms

Abstract

The present study was conducted to investigate the influence of drying condition (atmospheric pressure with varying temperature, acetone vapor-induced environment, and vacuum pressure) on the dehydration kinetics of carbamazepine dihydrate. Samples were prepared in loose crystals and agglomerated forms. Increasing driving forces, that is, higher temperature (up to 60°C), low vacuum pressure (10⁻³ Torr), and the presence of acetone vapor pressure (<20% P/P ₀), reduce the dehydration time. At higher temperatures, the effect of vacuum was negligible and did not enhance drying rates. The dihydrate has a higher affinity toward acetone vapors, where dehydration proceeds faster in a solvent vapor environment. Sorption of acetone molecules, however, was observed at higher partial pressures. The kinetics of dehydration show pronounced dependency on the crystal form; the agglomerated crystals dehydrate more rapidly than the loose crystals, and dehydration proceeds at a different controlling mechanism of the moisture removal process.

Keywords:

• Acetone
• Diffusion
• Pharmaceuticals
• SEM
• Vacuum

ACKNOWLEDGMENTS

The authors gratefully acknowledge the financial support provided by the Higher Education Funding Council for England (HEFCE) and Imperial College London for Ji Yi Khoo.

Notes

^a Activation energy published in previous work.^{[ 24 ]}