TY - JOUR T1 - Thermal Mechanical Analysis of Frozen Solutions of Mannitol and Some Related Stereoisomers: Evidence of Expansion during Warming and Correlation with Vial Breakage during Lyophilization JF - PDA Journal of Pharmaceutical Science and Technology JO - PDA J Pharm Sci Technol SP - 119 LP - 123 VL - 47 IS - 3 AU - N. Adeyinka Williams AU - N. Joyce Guglielmc Y1 - 1993/05/01 UR - http://journal.pda.org/content/47/3/119.abstract N2 - 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. ER -