Abstract
The effect of organic solvents on the degradation kinetics, products and mechanisms of Moexipril (1) was investigated at 25°C. Like those observed in aqueous solution, the degradation kinetics leading to the diketopiperazine (2) and hydrolysis product (3) in mixed solvents were found to be pseudo-first-order. Added organic solvent, however, produced a dramatic effect on the rate and product ratio of the degradation. Thus, the hydrolysis process ( k 3) was suppressed in solvents with high organic content. The two water or neutral catalyzed cyclizaation processes ( k 1 and k 2) responsible for the diketopiperazine formation, on the other hand, were enhanced by the addition of organic solvent; a maximum increase of 5.5 and 29-fold for k 1 and k 2, respectively, was observed in 75–90% ethanol solutions. Attempts were made to rationalize such rate enhancement through changes in solvation energy, p K a values of 1 and equilibrium constants of the intermediates with added organics. The application of the results to some of the formulation problems is discussed.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
