The role of viscoelastic properties in physical stability of freeze-dried solids: Crystallization of mannitol
Abstract
Effects of concentration, freezing rate, and noncrystallizing cosolute on the physical state of mannitol after freeze drying were investigated. When mannitol is present as a single solute, slow freezing of 10% (w/v) mannitol produces a mixture of the α and the β polymorphs, whereas fast freezing of the same solution produces the δ form. Fast freezing of 5% (w/v) mannitol results primarily in the β form. When a noncrystallizing cosolute is present, the relative threshold concentration above which crystalline mannitol is detected in the freeze-dried solid by x-ray diffraction is about 30% (w/w). Glass transition temperature of mixtures of mannitol and disaccharides are reasonably well predicted by the Gordon-Taylor equation. Crystallization of mannitol from freeze-dried solids during storage below Tg and the influence of viscoelastic properties of an amorphous solid below Tg on mannitol crystallization were studied. Fragility of freeze-dried solids was measured using two different methods. It was determined from measuring the width of the glass transition (ΔTg) and from measuring the enthalpy recovery due to molecular mobility below Tg using DSC. The data suggest that the fragility measurement from the enthalpy recovery data may be the more rigorous method. When mannitol/disaccharide mixtures were stored 10–15°C below their glass transition temperature, mannitol did not crystallize for at least 20-week period. When mannitol/sucrose (a fragile glass former) and mannitol/maltodextrin (a strong glass former) were stored at about 5°C below Tg, only mannitol/maltodextrin mixture showed an increase in mannitol crystallinity. This supports the hypothesis that mannitol is less likely to crystallize from the fragile glass mixture compared to the strong glass mixture. The reason is that at the same temperature interval below the glass transition temperature, (Tg-T), the fragile glass system will more quickly increase in viscosity and have less molecular mobility because of its narrow glass transition region.
Degree
Ph.D.
Advisors
Nail, Purdue University.
Subject Area
Physical chemistry|Food Science|Organic chemistry
Off-Campus Purdue Users:
To access this dissertation, please log in to our
proxy server.