Effects of sucrose, citric buffer and glucose oxidase on the stability of captopril in liquid formulations.
OBJECTIVE
To study the effects of sucrose, citric buffer and glucose oxidase on the stability of captopril in liquid formulations.


METHODS
Captopril liquid formulations 1 mg/ml were prepared in various concentrations of syrup with and without citric buffer. The liquid formulations were stored in amber glass bottles at 5 degrees C. Samples were removed from these formulations at 0, 1, 2, 3, 4, 7, 10, 15, 20 and 30 days for assay of captopril by a stability-indicating high performance liquid chromatographic method.


RESULTS
Our findings indicate that low concentration of citric buffer (0.03 M) had a small stabilising effect on captopril in liquid formulations containing no or low concentration of sucrose (10% w/v). However, in formulations with higher concentrations of sucrose (30 and 85% w/v, respectively), the stabilising effect was not apparent. Captopril in 1 mg/ml formulations containing 0.03 M citric buffer and 10% w/v glucose degraded rapidly in the presence of glucose oxidase. The degradation was particularly evident at higher temperature. Glucose oxidase is an antioxidant, which can extensively reduce oxygen concentration in liquid formulations.


CONCLUSIONS
The stability of captopril is very sensitive to the presence of excipients. Many excipients can function as catalysts in its degradation. Even in the deficiency of oxygen, its degradation can also be substantial with suitable catalysts present in the liquid formulation.
Liu
J
J
Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore.
Chan
S Y
SY
Ho
P C
PC
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000737:chemistry*; D002216:Captopril / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D019343:Citric Acid / Q000737:chemistry*; D004347:Drug Interactions; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry; D005949:Glucose Oxidase / Q000737:chemistry*; D010084:Oxidation-Reduction; D013395:Sucrose / Q000737:chemistry*
D000806:Angiotensin-Converting Enzyme Inhibitors; D005079:Excipients; D019343:Citric Acid; D013395:Sucrose; D002216:Captopril; D005949:Glucose Oxidase