THE PHYSICAL STATE OF MANNITOL AFTER FREEZE-DRYING - EFFECTS OF MANNITOL CONCENTRATION, FREEZING RATE, AND A NONCRYSTALLIZING COSOLUTE

The objectives of this study were to (1) measure the effects of freezi ng rate and mannitol concentration on the physical state of freeze-dri ed mannitol when mannitol is present as a single component, (2) determ ine the relative concentration threshold above which crystalline manni tol can be observed by X-ray powder diffraction in the freeze-dried so lid when a variety of noncrystallizing solutes are included in the for mulation, and (3) measure the glass transition temperature of amorphou s mannitol and to determine the degree to which the glass transition t emperature of freeze-dried solids consisting of mannitol and a disacch aride is predicted by the Gordon-Taylor equation. Both freezing rate a nd mannitol concentration influence the crystal form of mannitol in th e freeze-dried solid when mannitol is present as a single component. S low freezing of 10% (w/v) mannitol produces a mixture of the alpha and beta polymorphs, whereas fast freezing of the same solution produces the delta form. Fast freezing of 5% (w/v) mannitol results primarily i n the beta form. The threshold concentration above which crystalline m annitol is detected in the freeze-dried solid by X-ray diffraction is consistently about 30% (w/w) when a second, noncrystallizing solute is present, regardless of the nature of the second component. The glass transition temperature of amorphous mannitol measured from the quench- cooled melt is approximately 13 degrees C. Accordingly, mannitol is an effective plasticizer of freeze-dried solids when the mannitol remain s amorphous. Glass transition temperatures of mixtures of mannitol and the disaccharides sucrose, maltose, trehalose, and lactose are well p redicted by the Gordon-Taylor equation with values of k in the range o f 3 to 4.