| Autor: |
Pandit, Nivedita K., Hinderliter, Janet S. |
| Zdroj: |
Journal of Pharmaceutical Sciences; August 1985, Vol. 74 Issue: 8 p857-861, 5p |
| Abstrakt: |
The reaction of chlorthalidone with methanol to give the corresponding methyl ether was investigated. The kinetics are pseudo-first-order in chlorthalidone, but the observed pseudo-first-order rate constants show an unexpected dependence on the initial chlorthalidone concentration, attributable to the presence of trace catalytic impurities in commercial chlorthalidone. Evidence is presented to show that trace heavy metals are probably responsible for the primary catalytic effect. Trace quantities of acetic acid are also present and show a smaller secondary catalytic effect. Kinetics in the presence of added heavy metals and acetic acid were examined. EDTA and povidone reduce the degradation rate. Stabilization by EDTA is due to its ability to chelate heavy metals. Stabilization by povidone is also primarily due to its ability to complex heavy metals; complexation data of ferric and nickel ions with povidone and with 1-methyl-2-pyrrolidinone as a monomer model are presented. In addition, complexation constants were calculated for the interaction of povidone with chlorthalidone, which may also play a role in stabilization. |
| Databáze: |
Supplemental Index |
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