An Investigation Into the Subambient Behavior of Aqueous Mannitol Solutions Using Differential Scanning Calorimetry, Cold Stage Microscopy, and X-Ray Diffractometry

Abstract

The subambient behavior of aqueous mannitol solutions is of considerable relevance to the preparation of freeze dried formulations. In this investigation the properties of 3% w/v mannitol solutions were investigated using differential scanning calorimetry (DSC), cold stage microscopy (CSM), and X-ray diffraction (XRD) to identify the thermal transitions and structural transformations undergone by this system. It was found that on cooling from ambient the system formed ice at circa −20°C while a further exotherm was seen at approximately −30°C. Upon reheating an endotherm was seen at circa −30°C followed immediately by an exotherm at circa −25°C. Temperature cycling indicated that the thermal transitions observed upon reheating were not reversible. Modulated temperature DSC (MTDSC) indicated that the transitions observed upon reheating corresponded to a glass transition immediately followed by recrystallization, XRD data showed that recrystallization was into the β form. Annealing at −35°C for 40min prior to cooling and reheating resulted in a maximum enthalpy being observed for the reheating exotherm. It is concluded that on cooling 3% w/v aqueous mannitol solutions an amorphous phase is formed that subsequently recrystallises into the β form. The study has also shown that DSC, CSM, and XRD are useful complementary techniques for the study of frozen systems. © 2003 Wiley-Liss, Inc. and the American Pharmacists Association.