TY - JOUR
T1 - Reaction between drug substances and pharmaceutical excipients: Formation of esters between cetirizine and polyols
AU - Yu, He
AU - Cornett, Claus
AU - Larsen, Jesper
AU - Hansen, Steen Honore'
PY - 2010/11
Y1 - 2010/11
N2 - Reactions between active drug substances and excipients are of interest in the drug formulation process and should also be considered in the following storage of final preparations. Some excipients react more readily with certain chemical groups in drug substances and in the present paper the ester formation between a drug substance having a carboxylic acid moiety and some polyols are described. The drug substance cetirizine was chosen as the model substance as it is already marketed and used as a common drug for treatment of allergic reactions. Among the marketed products are oral solutions and oral drops containing excipients like sorbitol and glycerol. It was found that the carboxylic acid cetirizine readily reacts with sorbitol and glycerol to form monoesters. At a temperature as low as 40 °C, more than 1% of the cetirizine content was transformed into a monoester within 1 week using concentrations similar to those used in marketed preparations. The kinetic studies of the reaction performed at 40, 60 and 80 °C also revealed that the esters were unstable and they degraded especially at higher temperatures. Analysis of two marketed preparations having expiry dates in 2011 showed content of the cetirizine esters corresponding to a range from 0.1 to 0.3% of the declared cetirizine content.
AB - Reactions between active drug substances and excipients are of interest in the drug formulation process and should also be considered in the following storage of final preparations. Some excipients react more readily with certain chemical groups in drug substances and in the present paper the ester formation between a drug substance having a carboxylic acid moiety and some polyols are described. The drug substance cetirizine was chosen as the model substance as it is already marketed and used as a common drug for treatment of allergic reactions. Among the marketed products are oral solutions and oral drops containing excipients like sorbitol and glycerol. It was found that the carboxylic acid cetirizine readily reacts with sorbitol and glycerol to form monoesters. At a temperature as low as 40 °C, more than 1% of the cetirizine content was transformed into a monoester within 1 week using concentrations similar to those used in marketed preparations. The kinetic studies of the reaction performed at 40, 60 and 80 °C also revealed that the esters were unstable and they degraded especially at higher temperatures. Analysis of two marketed preparations having expiry dates in 2011 showed content of the cetirizine esters corresponding to a range from 0.1 to 0.3% of the declared cetirizine content.
KW - Former Faculty of Pharmaceutical Sciences
U2 - 10.1016/j.jpba.2010.05.001
DO - 10.1016/j.jpba.2010.05.001
M3 - Journal article
C2 - 20627436
SN - 0731-7085
VL - 53
SP - 745
EP - 750
JO - Journal of Pharmaceutical and Biomedical Analysis
JF - Journal of Pharmaceutical and Biomedical Analysis
ER -