The effect of polyvinylpyrrolidine on the stability of taurolidine.
In an aqueous solution, taurolidine reversibly degrades to taurultam, hydroxymethyltaurultam, taurineamide, and formaldehyde. The objectives of this research were to investigate the mechanism of polyvinylpyrrolidine (PVP)-induced taurolidine stabilization by measuring the effect of PVP on the rate and extent of formaldehyde release from taurolidine and its decomposition products, the ionization of taurineamide, and the NMR and FT-IR spectra of taurineamide. PVP was found to a) increase the rate constant for taurultam formation from taurineamide and formaldehyde, b) decrease the apparent pKa of taurineamide, and c) alter the NMR and FT-IR taurineamide spectra. The effect of PVP on the stability of taurolidine was to increase the stability of its primary degradation product, taurultam, which, in turn increased taurolidine stability because taurultam was reversibly formed from taurolidine. Furthermore, the increased stability of taurultam in acidic, aqueous PVP solutions was due to an increased rate of taurultam formation from its primary degradation products: taurineamide and formaldehyde. The rate constant for taurultam formation increased three-fold in the presence of 5% PVP. The rate increase was caused by the interaction of unprotonated taurineamide with PVP. The estimated taurineamide-PVP association constant was 1800 M-1. This interaction decreased the concentration of unreactive/protonated taurineamide while increasing the concentration of unprotonated/associated substrate which was found to be fivefold less reactive than the free/unprotonated amine.
Kirsch
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LE
Division of Pharmaceutics, College of Pharmacy, University of Iowa, Iowa City 52242, USA. lee-kirsch@uiowa.edu
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D000890:Anti-Infective Agents / Q000737:chemistry*; D004355:Drug Stability; D007477:Ions; D007700:Kinetics; D016014:Linear Models; D015394:Molecular Structure; D011205:Povidone / Q000737:chemistry*; D013654:Taurine / Q000031:analogs & derivatives* / Q000737:chemistry; D013829:Thiadiazines / Q000737:chemistry*
D000890:Anti-Infective Agents; D007477:Ions; D013829:Thiadiazines; D013654:Taurine; C012566:taurolidine; D011205:Povidone; C111424:taurultam; C111425:taurineamide