An accurate prediction of the pH change due to degradation: correction for a "produced" secondary buffering system.
Esmolol hydrochloride degrades in aqueous solutions by the hydrolysis of a labile aliphatic carboxyester group. The products are methanol and ASL-8123. The resulting aliphatic carboxylic acid moiety (ASL-8123) has a pK of 4.80, which is within 1 pH unit of the pH of the formulation. ASL-8123 therefore acts as a "secondary buffer" and minimizes the change in pH due to degradation. Equations are presented to calculate the change in the pH when the primary degradation product acts as a secondary buffer. This information can be used in the development of a parenteral product to predict, a priori, the concentration of buffer necessary for optimal pH maintenance. This knowledge can reduce the number of formulation screens required to determine the necessary buffer capacity for optimal drug stability.
Rosenberg
L S
LS
Product Development Section, Du Pont Critical Care, Waukegan, Illinois 60085.
Hostetler
C K
CK
Wagenknecht
D M
DM
Aunet
D A
DA
D002021:Buffers; D002626:Chemistry, Pharmaceutical; D004355:Drug Stability; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D011412:Propanolamines / Q000032:analysis
D002021:Buffers; D011412:Propanolamines; C036604:esmolol