Evaluation of cholecystokinin (CCK-8) peptide thermal stability for use as radiopharmaceutical by means isothermal and nonisothermal approaches.
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.
Oliva
A
A
Departamento de Ingeniería Química y Tecnología Farmacéutica, Facultad de Farmacia, Universidad de La Laguna, 38200, La Laguna, Tenerife, Spain. amoliva@ull.es
Hidalgo
M
M
Alvarez
C
C
Llabrés
M
M
Fariña
J B
JB
D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D019275:Radiopharmaceuticals / Q000737:chemistry*; D012844:Sincalide / Q000032:analysis / Q000737:chemistry*; D013696:Temperature
D019275:Radiopharmaceuticals; D012844:Sincalide