DeLuca P P
Dev Biol Stand. 1976 Oct;36:41-50.
The development of a suitable formulation and a freeze-dry cycle for a pharmaceutical dosage form requires knowledge of some basic properties such as (1) eutectic temperature, if one exists, (2) temperature effect on solubility, (3) degree of supercooling, (4) heat transfer properties of the frozen product and (5) equipment design and equipment capability. Basic work with several inorganic and organic salts shows that eutectic temperature is a function of the melting point and the differential heat of solution of a drug. From a knowledge of these parameters, a mathematical expression can be used to estimate eutectic temperature. The desired characteristics which can be achieved by proper formulation of the solution to be freeze-dried and by employing optimum freeze-drying cycles include an intact cake, sufficient strength, uniform color and rapid reconstitution. By utilizing resistivity measurements to determine eutectic temperature and supercooling properties it is possible to reformulate products, increase batch sizes and reduce overall times for freeze-drying cycles.
开发一种适合的药物剂型配方和冻干周期需要了解一些基本特性，例如：（1）共晶温度（若存在）；（2）温度对溶解度的影响；（3）过冷度；（4）冷冻产品的传热特性；以及（5）设备设计和设备性能。对几种无机和有机盐进行的基础研究表明，共晶温度是药物熔点和溶解微分热的函数。根据这些参数的知识，可以使用数学表达式来估算共晶温度。通过对待冻干溶液进行适当配方并采用最佳冻干周期，可以实现的理想特性包括完整的块状物、足够的强度、均匀的颜色和快速复溶。通过利用电阻率测量来确定共晶温度和过冷特性，可以重新设计产品配方、增加批次规模并缩短冻干周期的总体时间。
