RH-temperature stability diagram of α- and β-anhydrous and monohydrate lactose crystalline forms.

Lactose crystals exhibit polymorphic, deliquescent, and hydrate-forming traits and can exist in monohydrate, β-anhydrate, stable α-anhydrate, and hygroscopic α-anhydrate (isomorphic desolvate) forms. The objective of this study was to identify the relative humidity (RH) and temperature boundaries at which anhydrate-hydrate transitions and deliquescence occur for these lactose crystal forms. The deliquescence point (RH) of lactose monohydrate was determined by measuring the water activity (a) of a saturated solution, and the RHs of the anhydrates were determined using dynamic vapor sorption measurement techniques. Increasing temperatures from 20 to 50 °C resulted in decreases in RH from 99 to 98% RH for the monohydrate, 89 to 82% RH for the β-anhydrate, and 87 to 82% RH for the stable α-anhydrate. The effects of temperature on the anhydrate-hydrate RH boundaries were determined using a combination of controlled a equilibration, powder X-ray diffraction, and Fourier-transform infrared spectroscopy techniques. Increasing temperature from 20 to 50 °C resulted in increasing RHs of the anhydrate-to-hydrate boundaries: the β-anhydrate-to-monohydrate boundary increased from 77 to 79% RH, the stable α-anhydrate-to-monohydrate from 63 to 79% RH, and the unstable α-anhydrate-to-monohydrate from 10 to 13% RH. This is the first report of an RH-temperature stability map for lactose crystalline forms.