PT  - JOURNAL ARTICLE
AU  - Williams, N. Adeyinka
AU  - Guglielmc, N. Joyce
TI  - Thermal Mechanical Analysis of Frozen Solutions of Mannitol and Some Related Stereoisomers: Evidence of Expansion during Warming and Correlation with Vial Breakage during Lyophilization
DP  - 1993 May 01
TA  - PDA Journal of Pharmaceutical Science and Technology
PG  - 119--123
VI  - 47
IP  - 3
4099  - http://journal.pda.org/content/47/3/119.short
4100  - http://journal.pda.org/content/47/3/119.full
SO  - PDA J Pharm Sci Technol1993 May 01; 47
AB  - The mechanical properties of frozen mannitol, L-iditol, dulcitol, and sorbitol solutions were measured as a function of temperature during warming (after freezing) using a thermal mechanical analyzer (TMA). The mannitol sample first underwent a contractive phase starting at –30°C and ending at –25°C. This was followed by an initially rapid, then less rapid expansive phase which continued until melting occurred. These events provide direct evidence that mannitol solutions undergo an expansion during warming after “fast” freezing and also corroborate the vial breakage observed when mannitol solutions are frozen and thawed or freeze-dried in glass vials. Of the other stereoisomers studied, only dulcitol had an expansive phase although at a slower rate than mannitol. Its solution was found to cause vial breakage also but only at fill volumes higher than mannitol fill volumes. TMA is a useful technique for studying dimensional changes in the frozen state, with important implications for solving vial breakage problems in freeze-drying.