Chemical degradation kinetics of fibrates: bezafibrate, ciprofibrate and fenofibrate

Abstract

Fibrates are drugs used for the treatment of hypertriglyceridemia and for the prevention of atherosclerosis. Three drugs in the fibrate class, ciprofibrate, fenofibrate and bezafibrate, were chosen for this study because their raw materials are readily available and because scientific publications on these compounds is limited. To evaluate their intrinsic stability, the drugs were exposed to a test condition (temperature, oxidation, UV light exposure, hydrolysis at different pH values and metal ions in solution) and then were subjected to analysis by HPLC. The samples were run on a C18 column, with a flow rate of 1.0 mL min -1 in a mobile phase consisting of methanol: 0.01 % phosphoric acid v/v (80:20), with variable detection wavelengths in the UV spectra. The analysis methodology showed satisfactory performance parameters. The three drugs were very unstable, degrading in each of the conditions evaluated. The test conditions of acid and basic hydrolysis showed the most significant degradation. The results demonstrated that the drugs in this class are unstable. Based on these experimentally determined degradation kinetics, it is easy to understand and emphasize the importance of the lack of liquid dosage forms on the market for fibrates because of their instability.Uniterms: Hypertriglyceridemia/fibrates. Fibrates stability/study. Fibrates degradation products/High Perfomance Liquid Chromatography (HPLC). Fibrates/Degradation kinetics. INTRODUCTIONFibrates are drugs used for the treatment of hypertriglyceridemia and for the prevention of atherosclerosis, and are represented by the following compounds: clorfibrate, ciprofibrate, bezafibrate, fenofibrate and geozila. Fibrates decrease triglyceride levels and increase HDL-C levels, the latter effect is more pronounced in patients with hypertriglyceridemia. The effect on LDL-C levels varies. They may reduce LDL-C levels in patients with low triglycerides, but may paradoxically increase levels for patients with high triglyceride levels. Fibrates also significantly reduce the levels of highly atherogenic remnant lipoproteins, and are more efficient than statins in doing so (Schulz, 2006).Among the fibrates, three drugs were chosen for the execution of this project: ciprofibrate, fenofibrate and bezafibrate (Figure 1). The drugs were chosen based on the availability of raw materials and evidence of few scientific publications regarding the drugs on the subject of research.Some analytical methods have been developed for the analysis of ciprofibrate, fenofibrate and bezafibrate by HPLC/UV (Nascimento et al., 2011;Salama et al., 2011;Jain et al., 2012;Kumbhar et al., 2013;Wei et al., 2008). The vast majority of these analytical methodologies used reverse phase columns, mainly octadecyl silane, with a controlled acidic pH solution for the mobile phase and detection in the ultraviolet range.Few articles have been published on the stability of the chosen fibrates (Salama et al., 2011;Jain et al., 2012;Kumbhar et al., 2013), and none were found that identified degradation pro...

Visualizing the Journey of Fenofibrate through the Rat Gastrointestinal Tract by Matrix-Assisted Laser Desorption/Ionization–Mass Spectrometry Imaging

“…The hydrolysis of fenofibrate to fenofibric acid in the stomach had to the authors’ knowledge not been reported in vivo before. However, previous in vitro studies found significant instability of fenofibrate when a fenofibrate/methanol mixture was incubated with 0.1 M HCl for 4 h at 50 °C . The pH in the rat stomach has been found to be ranging from 1.9 ± 0.3 in the forestomach to 2.9 ± 0.7 in the glandular stomach, which supported that fenofibrate might be hydrolyzed into fenofibric acid by the acidic pH in the stomach in the current study.…”

Study of the Oxidative Forced Degradation of Glutathione in Its Nutraceutical Formulations Using Zone Fluidics and Green Liquid Chromatography

“…In our case, since the oxidant is in great excess, and it is practically not consumed, the reaction follows pseudo-first- Separations 2020, 7, x FOR PEER REVIEW 7 of 11 research using mass spectrometric detection intends to identify all oxidative by-products of GSH and to propose a stability-indicating method suitable for their quantification. The order of the oxidation reaction of GSH with H2O2 was evaluated by fitting three kinetic models, i.e., zero, first and second order [25]. As can be seen in Figures 5 and 6, using both HPLC and SI, the linearity was excellent for the first-order oxidation kinetics model (r > 0.99).…”

“…The order of the oxidation reaction of GSH with H 2 O 2 was evaluated by fitting three kinetic models, i.e., zero, first and second order [25]. As can be seen in Figures 5 and 6, using both HPLC and SI, the linearity was excellent for the first-order oxidation kinetics model (r > 0.99).…”

Ciprofibrate-Loaded Nanoparticles Prepared by Nanoprecipitation: Synthesis, Characterization, and Drug Release

“…In pharmaceutical development, there is considerable interest in crystal structure investigations, as a way to understand how their structures (either amorphous or crystalline) and properties such as density, size, and particle shape correlate to other physicochemical properties, aiming the optimization of these drugs for solid dosage [ 5 ].…”