Freeze Drying of Pharmaceuticals. Eutectic Temperature and Collapse Temperature of Solute Matrix upon Freeze Drying of Three-Component Sytems

概要

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For the model solution of the parenteral formulation, four ternary solutions were used : NaCl-KCl-H_2O with 10% of total solutes, NaCl-mannitol-H_2O, NaCl-glycine-H_2O and mannitol-sorbitol-H_2O with 5%. Measurements were carried out on the electrical resistance and the temperature of the sample solution during cooling and rewarming, and the change of the macroscopic appearance of the frozen sample during freeze drying was observed. The eutectic temperature T_e and the collapse temperature T_c of the solute matrix were derived from above measurements and observation. The mechanism of the collapse during freeze drying was discussed in relation to the state of frozen sample and T_c was classified in three types : the first was related to T_e, the second to a glass transition temperature T_g and the third was the temperature below which the gross matrix of crystallized solute persisted even in the presence of a small amount of solution among crystallized solutes and ice crystals. From the properties of supercooled aqueous solution, it was found that the solution which did not exhibit eutectic crystallization could be freeze-dried if the temperature of sample was controlled below T_c. It was also suggested that the difficulty of freeze drying of the solution with low T_c could be improved by addition of a suitable solute.
社団法人日本薬学会の論文
1971-06-25