+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Application of a two-state kinetic model to the heterogeneous kinetics of reaction between cysteine and hydrogen peroxide in amorphous lyophiles



Application of a two-state kinetic model to the heterogeneous kinetics of reaction between cysteine and hydrogen peroxide in amorphous lyophiles



Journal of Pharmaceutical Sciences 97(9): 3907-3926



The bimolecular reaction between cysteine (CSH) and hydrogen peroxide (H(2)O(2)) in amorphous PVP and trehalose lyophiles has been examined at different reactant and excipient concentrations and at varying pH and temperature. Initial rates of product formation and complete reactant and product concentration-time profiles were generated by HPLC analyses of reconstituted solutions of lyophiles stored for various periods of time. While only cystine (CSSC) forms in aqueous solutions, cysteine sulfinic (CSO(2)H) and sulfonic (CSO(3)H) acids are significant degradants in amorphous solids. The formation of alternative degradants was consistent with the solution reaction mechanism, which involves a reactive sulfenic acid (CSOH) intermediate, coupled with the restricted mobility in the amorphous solid-state, which favors reaction of CSOH with the smaller, mobility-advantaged H(2)O(2) over its reaction with cysteine. Complex rate laws (i.e., deviations from 1st order for each reactant) observed in initial rate studies and biphasic concentration-time profiles in PVP were successfully fitted by a two-state kinetic model assuming two reactant populations with different reactivities. The highly reactive population forms CSSC preferentially while the less reactive population generates primarily sulfinic and sulfonic acids. Reactions in trehalose could be described by a simple one-state model. In contrast to the reaction in aqueous solutions, the 'pH' effect was minimal in amorphous solids, suggesting a change in the rate-determining step to diffusion control for the model reaction occurring in amorphous lyophiles.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 051607795

Download citation: RISBibTeXText

PMID: 18200535

DOI: 10.1002/jps.21257


Related references

Kinetics and mechanism for the reaction of cysteine with hydrogen peroxide in amorphous polyvinylpyrrolidone lyophiles. Pharmaceutical Research 23(10): 2239-2253, 2006

Revisiting a proposed kinetic model for the reaction of cysteine and hydrogen peroxide via cysteine sulfenic acid. International Journal of Chemical Kinetics 39(1): 32-38, 2007

Model Of Chemical Reaction Kinetics For Calculating Detonation Processes In Gas And Heterogeneous Mixtures Containing Hydrogen Peroxide. Combustion Science and Technology 178(5): 895-919, 2006

Kinetics and mechanism of the reaction of cysteine and hydrogen peroxide in aqueous solution. Journal of Pharmaceutical Sciences 94(2): 304-316, 2005

On the kinetics and mechanism of the reaction of cysteine and hydrogen peroxide in aqueous solution. Journal of Pharmaceutical Sciences 95(1): 15-18, 2006

Kinetics and mechanisms of deamidation and covalent amide-linked adduct formation in amorphous lyophiles of a model asparagine-containing Peptide. Pharmaceutical Research 29(10): 2722-2737, 2012

A mechanism-based kinetic analysis of succinimide-mediated deamidation, racemization, and covalent adduct formation in a model peptide in amorphous lyophiles. Journal of Pharmaceutical Sciences 101(9): 3096-3109, 2012

Kinetics and mechanisms of heterogeneous reaction of gaseous hydrogen peroxide on mineral oxide particles. Environmental Science and Technology 45(8): 3317-3324, 2011

Kinetics of Heterogeneous Reaction of Sulfur Dioxide on Authentic Mineral Dust: Effects of Relative Humidity and Hydrogen Peroxide. Environmental Science and Technology 49(18): 10797-10805, 2015

First-principles-based reaction kinetics from reactive molecular dynamics simulations: Application to hydrogen peroxide decomposition. Proceedings of the National Academy of Sciences of the United States of America 116(37): 18202-18208, 2019

Kinetic study of the transient phase of a second-order chemical reaction coupled to an enzymic step: application to the oxidation of chlorpromazine by peroxidase-hydrogen peroxide. Biochimica et Biophysica Acta 831(3): 313-320, 1985

Kinetics of heterogeneous decomposition of hydrogen peroxide. Journal of Inclusion Phenomena and Macrocyclic Chemistry 4(4): 359-367, 1986

Kinetics of the reaction of the heaviest hydrogen atom with H2, the 4Heμ + H2 → 4HeμH + H reaction: experiments, accurate quantal calculations, and variational transition state theory, including kinetic isotope effects for a factor of 36.1 in isotopic mass. Journal of Chemical Physics 135(18): 184310, 2011

Time measurement-visual analysis of L-cysteine using the autocatalytic sodium sulfite/hydrogen peroxide reaction system and its application to length detection-flow analysis. Talanta 79(4): 1154-1160, 2009

Kinetic study of the effects of calcium ions on cationic artichoke (Cynara scolymus L.) peroxidase: calcium binding, steady-state kinetics and reactions with hydrogen peroxide. Biochimie 86(9-10): 667-676, 2004