Oliva A, Hidalgo M, Alvarez C, Llabrés M, Fariña J B
Departamento de Ingeniería Química y Tecnología Farmacéutica, Facultad de Farmacia, Universidad de La Laguna, 38200, La Laguna, Tenerife, Spain.
Drug Dev Ind Pharm. 2006 Sep;32(8):947-53. doi: 10.1080/03639040600599855.
The purpose of this research was to study the thermal stability of cholecystokinin octapeptide (CCK-8) in aqueous solution at pH 12 and ionic strength 0.01 M, which were kept as constants, by using isothermal and nonisothermal methods. The isothermal decomposition of CCK-8 was investigated as a function of temperature (40 degrees C to 70 degrees C). Nonisothermal stability studies were performed using a linear increasing temperature program. Two different nonisothermal studies were carried out at 0.25 degrees K and 0.5 degrees K per hour, and the temperature interval varied from 40 degrees C to 82 degrees C. The degradation of CCK-8 followed first-order kinetics, obeying the Arrhenius equation in the experimental temperature range. This indicated that the degradation mechanism of CCK-8 could be the equal within the temperature range studied. The nonisothermal approach resulted in activation energy (Ea) and shelf-life (t90%) values that agree well with those obtained by the isothermal method. The level of uncertainty in the estimates of t90% and Ea values is determined mainly by the extent of drug degradation and temperature change during the experiment. Therefore, nonisothermal experiments save time, labor and materials (i.e. the amount of drugs necessary to conduct the experiment) compared to the classic isothermal experiments, if they are performed using a suitable experimental design and a precise analytical method.
本研究的目的是通过等温法和非等温法,研究在pH值为12、离子强度为0.01 M(保持恒定)的水溶液中,八肽胆囊收缩素(CCK - 8)的热稳定性。研究了CCK - 8在40℃至70℃温度范围内的等温分解情况。采用线性升温程序进行非等温稳定性研究。以每小时0.25 K和0.5 K的升温速率进行了两种不同的非等温研究,温度区间为40℃至82℃。CCK - 8的降解遵循一级动力学,在实验温度范围内符合Arrhenius方程。这表明在研究的温度范围内,CCK - 8的降解机制可能是相同的。非等温法得到的活化能(Ea)和有效期(t90%)值与等温法得到的值吻合良好。t90%和Ea值估计的不确定程度主要取决于实验过程中药物的降解程度和温度变化。因此,如果采用合适的实验设计和精确的分析方法,与经典的等温实验相比,非等温实验节省时间、人力和材料(即进行实验所需的药物量)。