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KMID : 0043319810040020109
Archives of Pharmacal Research
1981 Volume.4 No. 2 p.109 ~ p.115
Stability of Pipethanate Hydrochloride in Aqueous Solution
Kim CK
Cha HS
Abstract
In the present investigation, an attempt has been made to apply the methods of classical chemical kinetics to the hydrolytic reaction of pipethanate hydrochloride. By successively keeping all but one variable essentially constant, it has been possible to resolve the overall effect of the individual contributing factors. Since nearly all commercial pipethanate preparations are formulated with antacid, studies were made at several constant hydrogen ion concentration ranging pH 0.4 to 7.5. Rate measurement was also carried out in temperature ranging from 25oC to 60oC. The hydrolysis of pipethanate is found to be of first order with respect to pipethanate concentration over an experimental range of hydrogen ion concentration (pH 0.4-7.5). The apparent activation energy(Ea) at pH 7.5 is 18.30Kcal/mole and the frequency factor is 1.1408 x 109 sec-1. In the present investigation, an attempt has been made to apply the methods of classical chemical kinetics to the hydrolytic reaction of pipethanate hydrochloride. By successively keeping all but one variable essentially constant, it has been possible to resolve the overall effect of the individual contributing factors. Since nearly all commercial pipethanate preparations are formulated with antacid, studies were made at several constant hydrogen ion concentration ranging pH 0.4 to 7.5. Rate measurement was also carried out in temperature ranging from 25oC to 60oC. The hydrolysis of pipethanate is found to be of first order with respect to pipethanate concentration over an experimental range of hydrogen ion concentration (pH 0.4-7.5). The apparent activation energy(Ea) at pH 7.5 is 18.30Kcal/mole and the frequency factor is 1.1408 X 109 sec-1. The rate of the hydrolysis has a minimum at pH 2.5-3.5. In this region the half-life of pipethanate was about 15.3 days at 60oC. The catalytic effect of water was found to be KH2O = 3.16 X 10-5min-1 at 60oC. The catalytic constants of the hydroxyl ions and hydrogen ions at 60oC were also found to be KOH = 4.5519 X 105min-1 and KH = 1.1568 X 10-2min-1, respectively. This reaction appears to be primarily base catalyzed hydrolysis and pipethanate is relatively reluctant toward acid catalyzed hydrolysis. A positive primary salt effect was noted in the solution of pipethanate at pH 7.5 and at 60oC.
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