Glass Fragility and the Stability of Pharmaceutical Preparations—Excipient Selection

ABSTRACT

The objectives of this study were, first, to calculate the zero mobility temperatures, T_o, of trehalose and sucrose by the Pikal method from the width of the glass transition and compare these to the literature, obtained by enthalpy relaxation measurement, and second, to compare the T_o values and physicochemical properties of trehalose to those of sucrose intern of potential to stabilize labile actives in the glassy state. Differential scanning calorimetry and coulometric Karl-Fischer analysis were used. The glass transition temperatures, T^g, for the two carbohydrates at circa 0.7% moisture were 101°C and 64°C for trehalose and sucrose, respectively. Anhydrous amorphous trehalose had a T_g of 116°C. The T_o values were found to be 44 and 3.5°C for trehalose and sucrose, respectively. The T_g - T_o value for sucrose was compared, and found to be in good agreement with that found by enthalpy relaxation measurements. Trehalose was found to be resistant to crystallization above the glass temperature. The study supports the validity of the calculation method proposed by Pikal for T_o. It has been proposed in the literature that T_o is a better measure of stability than T_g. Trehalose has a significantly higher T_o than sucrose and thus would work more effectively in stabilizing a labile active.

Key Words: :

• Carbohydrate glass
• Fragility
• Glass transition
• Stability
• Sucrose
• T_o: Trehalose