Photodegradation of Moxifloxacin in Aqueous and Organic Solvents: A Kinetic Study

Abstract

The kinetics of photodegradation of moxifloxacin (MF) in aqueous solution (pH 2.0-12.0), and organic solvents has been studied. MF photodegradation is a specific acid-base catalyzed reaction and follows first-order kinetics. The apparent first-order rate constants (kobs) for the photodegradation of MF range from 0.69 × 10(-4) (pH 7.5) to 19.50 × 10(-4) min(-1) (pH 12.0), and in organic solvents from 1.24 × 10(-4) (1-butanol) to 2.04 × 10(-4) min(-1) (acetonitrile). The second-order rate constant (k2) for the [H(+)]-catalyzed and [OH(-)]-catalyzed reactions are 6.61 × 10(-2) and 19.20 × 10(-2) M(-1) min(-1), respectively. This indicates that the specific base-catalyzed reaction is about three-fold faster than that of the specific acid-catalyzed reaction probably as a result of the rapid cleavage of diazabicyclononane side chain in the molecule. The kobs-pH profile for the degradation reactions is a V-shaped curve indicating specific acid-base catalysis. The minimum rate of photodegradation at pH 7-8 is due to the presence of zwitterionic species. There is a linear relation between kobs and the dielectric constant and an inverse relation between kobs and the viscosity of the solvent. Some photodegraded products of MF have been identified and pathways proposed for their formation in acid and alkaline solutions.

Role of stable hydrogen isotope variations in water for drug dissolution managing

“…Taking into account the previously obtained results on the rate of moxifloxacin degradation in organic solvents [66][67][68], we propose the unique analytical approach that is offered, consisting of an increase in speed of dissolution of slightly soluble and hydrophobic substances on the basis of variation in the isotope composition of water.…”

Photostability and Photostabilization of Drugs and Drug Products

“…The choice of an appropriate solvent or a solvent combination may improve the photostability of a particular drug. In particular, the effect of the dielectric constant on the kinetics of the photodegradation of 10-methylisoalloxazine [62], formylmethylflavin [65], riboflavin [72,[189][190][191][192][193], moxifloxacin [194], and norfloxacin [195,196] in aqueous and organic solvents has been studied. The reaction rates of these compounds are a linear function of the solvent dielectric constant.…”

“…The photodegradation rate of a drug may also be influenced by the solvent viscosity. In the case of the abovementioned flavins [62,65,192] and fluoroquinolones [193][194][195], the reaction rates are a reciprocal function of the solvent viscosity. Thus, an increase in the medium viscosity leads to a decrease in the reaction rate.…”

“…The oxidation of many drugs is affected by pH; for example, ascorbic acid (p a = 4.17) undergoes rapid photooxidation in the neutral and alkaline pH range and is stable in the acid pH range [197]. Several studies have been conducted to evaluate the effect of pH on the stability of the drug substances [14,198] and to assess the optimum pH from the rate-pH relationships to achieve stabilization [14,45,194,195,199]. The buffer species present in a solution may be involved in the general acid-base catalysis [18] and should be carefully selected to avoid this effect.…”

Structural elucidation of gemifloxacin mesylate degradation product

“…The stability of the fluorquinolones class is much studied and there are many papers describing the isolation and identification of degradation products of these drugs. The main degradation factor of fluorquinolones is the UV radiation, showing mainly modifications in the piperazine and diazabicyclo rings of these molecules (Burhenne et al, 1999;Lovdahl and Priebe, 2000;Hubicka et al, 2013;Ahmad et al, 2014), but the loss of the cyclopropyl group, hydroxylation of the substituent in position 7, dechlorination and defluorination are also described in the literature (Engler et al, 1998;Fasani et al, 1999;Lovdahl and Priebe, 2000;Hubicka et al, 2014). The decarboxylation of lomefloxacin, moxifloxacin hydrochloride and sparfloxacin under acid conditions was described by Salem et al (2006).…”