Chemical degradation kinetics of fibrates: bezafibrate, ciprofibrate and fenofibrate

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

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

Samaras of Austroplenckia Populnea (Celastraceae) : new constituents and effect of extracts and friedelin on germination of Bidens Pilosa (Asteraceae).

Objective: Evaluation of the impact of extracts and constituents from samaras of Austroplenckia populnea on percentage of seed germination (%SG), germination speed index (GSI), length of rootlets (LR), seedling length (SL), and on dry mass (DM) of Bidens pilosa L weed. Methods: The powder of samaras was extracted with organic solvents providing the hexane (SAPEH), chloroform (SAPEC), ethyl acetate (SAPEAE) and ethanol (SAPEE) extracts. The terpene 1 was isolated from SAPEH by means of column and thin layer chromatography and identified through NMR spectroscopy. Each extract and 1 were subjected to growth inhibition assays evaluating the following parameters: %SG, GSI, LR, SL and DM, with five repetitions. Results: The compounds Friedelin (1), 7-hydroxy-clerodan-3-en-16,15:18,20-diolide (2), 3,5,7,4'-tetrahydroxy-6-methoxy-8-prenylflavanone (3), tetradecanamide (4), and 4-hydroxy-1,6,15-acetyloxy-8,9-benzoyloxy-agarofurane (5) were isolated from hexane extract of samaras of A. populnea and identified by spectroscopic data. The compounds 2, 3 and 5 were not previously described as being chemical constituents from Celastraceae family. In addition, the novel compounds 3 and 5 were described here for the first time. Substantial effect on the germination of B. pilosa L. (pic?opreto) was observed after treatment of seeds with nonpolar extracts from Samaras of A. populnea. Friedelin inhibited the seed germination in the tested concentrations showing toxic properties against pic?o-preto. Conclusion: The germination inhibition of seeds was higher using nonpolar extracts than polar extract. Friedelin inhibited the seed germination in the tested concentrations showing toxic properties against B. pilosa

Insignificant level of in vitro cytotoxicity, anti?rotavirus, antibacterial, and antifungal activities of N?alkylmaleamic acids.

By reacting maleic anhydride with amines, we synthesized the derivatives N?ethyl, N?(2?ethylamine), N?piperidinyl, N?phenyl, and N?phenylhydrazinyl maleamic acids. The purity of these products was initially verified by melting range and the presence of only one spot observed by thin layer chromatography. The chemical structures of the obtained N?alkyl maleamic acids were confirmed through infrared (IR) and hydrogen and carbon nuclear magnetic resonance (1 H and 13C NMR) spectrometry. Due to the already proven pharmacological activity of maleimides, maleic anhydride and its N?alkyl maleamic acids were subjected to in vitro assays to observe antiviral (SA?11 rotavirus), antibacterial (Escherichia coli, Staphylococcus aureus, and Bacillus cereus), antifungal (Colletotrichum musae, Fusarium solani f. sp. phaseoli, Fusarium solani f. sp. piperis Alb., and Penicillium sp.), and antiprotozoal (Trichomonas vaginalis, Giardia lamblia, and Entamoeba histolytica) effects. To study the anti?rotavirus properties, firstly the 3?(4,5?dimethylthiazol?2?yl)?2?5?diphenyltetrazolium bromide (MTT) method was used to establish the median cytotoxicity concentration (CC50) of the compounds, using MA?104 cell line. Under the experimental conditions used, cytotoxic, anti?rotavirus, antibacterial, and antifungal properties were not observed for these compounds