Influence of water activity in organic solvent + water mixtures on the nature of the crystallizing drug phase. 1. Theophylline

Probing Pseudopolymorphic Transitions in Pharmaceutical Solids using Raman Spectroscopy: Hydration and Dehydration of Theophylline

“…In the case of TPa, the value of the critical RH is controversial and values ranging from 25% to 82% (for temperatures around 258C) have been reported. 44,47,70 Figure 6a shows the Raman spectra, in the region of 3060-3160 cm À1 , obtained for samples of TPa (commercial powder) stored at different RH values for 1 week at 228C, and illustrates the general behavior observed in all the studied regions. The corresponding plot of a h ratio versus RH is shown in Figure 6b.…”

“…TPa conversion have not been evaluated. Zhu et al 70 report a value of 0.25 for the critical water activity for TP solutions in organic solvent þ water mixtures. However, this value gives no clues concerning the behavior of samples exposed to atmosphere RH conditions, since it refers to direct contact with the solvent in TPhðsolidÞ !…”

Significance of controlling crystallization mechanisms and kinetics in pharmaceutical systems

“…Because crystallization provides a way of reducing the free energy of metastable thermodynamic states, the extent to which metastable states can be maintained is determined by the crystallization mechanisms and kinetics. [5][6][7][8][9][10][11][12][13][14][15][16] What is surprising, however, is that despite the important role that crystallization has in process control and in determining solid-phase outcomes, crystallization phenomena are often neglected in the pharmaceutical industry until a problem is encountered.…”

Efficient Co-crystal Screening Using Solution-Mediated Phase Transformation

“…This theoretical treatment of hydrate stability is well established and has been applied to numerous systems. 13 Water can be present either in the liquid state (neat or in solution) or in the gas state as water vapor, although kinetic effects may slow the transition to the hydrate in the latter.…”