Vial breakage by frozen mannitol solutions: correlation with thermal characteristics and effect of stereoisomerism, additives, and vial configuration.

The thermal characteristics as a function of cooling rate of mannitol solutions were studied by Differential Scanning Calorimetry (DSC). The exotherm appearing during warming at -25 +/- 1 degree C could be correlated with the temperature at which frozen mannitol solutions broke vials during warming. This temperature was also consistent with the temperature at which a sharp increase in resistance was reported in a preceding paper. The DSC exotherm did not appear to be due to crystallization of amorphous mannitol but rather to some other type of solid state transition. The peak was initially broadened and then obliterated by increasing amounts of additives such as lactose, glycine, potassium chloride, and sodium chloride. The presence of these ingredients in small amounts (less than 1% of the mannitol concentration) significantly reduced or prevented breakage. Other stereoisomers of mannitol, e.g., sorbitol and dulcitol, did not show any exotherm or break vials on freezing and thawing. It was also found that different types of vials exhibited different susceptibilities to breakage.