Water Activity-Mediated Control of Crystalline Phases of an Active Pharmaceutical Ingredient

Abstract

The thermogravimetry (TG) results (Figure 1) for Form A were obtained at a heating rate of 10 °C/min under nitrogen atmosphere. A weight loss of 0.07% was observed up to 100.6C and 0.82% up to 254.2C . Differential scanning calorimetry (DSC) results (Figure 2) for Form A were collected at a heating rate of 10 °C/min, under nitrogen atmosphere in an open pan. No melting transition was observed.

Thermodynamic Stability Considerations for Isostructural Dehydrates

“…However, these solvent-based methods are inappropriate for nonstoichiometric channel hydrates as this class of crystalline solids is known to lose water and incorporate new solvents when suspended in nonaqueous solvent media. 19 The stability relationship between Forms A and C was thus determined using solid-state thermal methods. A solid-state physical stability assessment, as a function of temperature and RH, was also utilized to support the results of the thermal analyses.…”

A Multi-Technique Approach to the Study of Structural Stability and Desolvation of Two Unusual Channel Hydrate Solvates of Finasteride

“…The pharmaceutical manufacture of a drug substance and subsequent development of a drug product will generally, at some stage in the program, involve interactions between a solvent and the active pharmaceutical ingredients or excipients. This may, for example, include recrystallisation1 and drying of the drug substance, wet granulation with excipients in the presence of an appropriate solvent,2 lyophilisation, or spray drying. Solvent interactions can be critical to the quality and performance of the final product,2,3,4 whether it be through controlling the polymorphic form, formation of solvates, or desolvation.…”

Improved pharmacokinetics of mercaptopurine afforded by a thermally robust hemihydrate

“…Not only does the hemihydrate have higher thermal stability towards dehydration than the monohydrate form, it is, to our knowledge, the highest dehydration temperature for any single component organic molecule in literature. 13-17 Also, the hemihydrate form showed better stability to aqueous conversion than the anhydrate form. Finally, the hemihydrate has double the water solubility as well as almost three times the in vivo bioavailability of the commercially used form.…”