Degradation kinetics of somatostatin in aqueous solution.
The degradation kinetics of somatostatin (somatotropin release inhibiting factor), a cyclic tetradecapeptide, was investigated as a function of temperature, pH, ionic strength, buffer type, and buffer concentration. In addition, the effect of different container materials in which the solutions were stored and the presence of an antimicrobial agent for in vitro use was examined. The degradation of somatostatin followed first-order kinetics under all investigated conditions. The pH-stability profile showed a well-defined stability optimum around pH 3.7. The degradation was accelerated at higher buffer concentrations, phosphate buffer being significantly more detrimental than acetate buffer. The ionic strength and the drug concentration had virtually no effect on the degradation rate. When general purpose glass vials were used as storage containers, degradation was faster due to release of alkali from the container material. The solution properties, i.e., pH, buffer type, buffer capacity, and the experimental setup such as container material and sterile conditions need to be carefully selected or maintained, in order to avoid accelerated degradation.
Herrmann
Joachim
J
Dr. Willmar Schwabe Pharmaceuticals, Karlsruhe, Germany. joachim.herrmann@schwabe.de
Bodmeier
Roland
R
D004305:Dose-Response Relationship, Drug; D019999:Pharmaceutical Solutions / Q000493:pharmacokinetics; D013004:Somatostatin / Q000493:pharmacokinetics*; D014867:Water / Q000378:metabolism*
D019999:Pharmaceutical Solutions; D014867:Water; D013004:Somatostatin