THERMAL-MECHANICAL ANALYSIS OF FROZEN-SOLUTIONS OF MANNITOL AND SOME RELATED STEREOISOMERS - EVIDENCE OF EXPANSION DURING WARMING AND CORRELATION WITH VIAL BREAKAGE DURING LYOPHILIZATION

The mechanical properties of frozen mannitol, L-iditol, dulcitol, and sorbitol solutions were measured as a function of temperature during w arming (after freezing) using a thermal mechanical analyzer (TMA). The mannitol sample first underwent a contractive phase starting at -30-d egrees-C and ending at -25-degrees-C. This was followed by an initiall y rapid, then less rapid expansive phase which continued until melting occurred. These events provide direct evidence that mannitol solution s undergo an expansion during warming after ''fast'' freezing and also corroborate the vial breakage observed when mannitol solutions are fr ozen and thawed or freeze-dried in glass vials. Of the other stereoiso mers studied, only dulcitol had an expansive phase although at a slowe r rate than mannitol. Its solution was found to cause vial breakage al so but only at fill volumes higher than mannitol fill volumes. TMA is a useful technique for studying dimensional changes in the frozen stat e, with important implications for solving vial breakage problems in f reeze-drying.