Electrochemical studies and square-wave voltammetric determination of fenofibrate in pharmaceutical formulations

The electrochemical reduction of fenofibrate at a hanging mercury drop electrode (HMDE) was investigated by cyclic voltammetry, square-wave voltammetry, and chronoamperometry. Different buffer solutions were used over a wide pH range (3.0–10.0). The best definition of the analytical signals was found in borate buffer (pH 9.0)–tetrabutylammonium iodide mixture containing 12.5% (v/v) methanol at –1.2 V (versus Ag/AgCl). According to cyclic voltammetric studies, the reduction was irreversible and diffusion controlled. The diffusion coefficient was 2.38×10^–6 cm² s^–1 as determined by chronoamperometry. Under optimized conditions of square-wave voltammetry, a linear relationship was obtained between 0.146–4.96 g mL^–1 of fenofibrate with a limit of detection of 0.025 g mL^–1. Validation parameters such as sensitivity, accuracy, precision, and recovery were evaluated. The proposed method was applied to the determination of fenofibrate in pharmaceutical formulations. The results were compared with those obtained by a published high-performance liquid chromatography method. No difference was found statistically.     

Preparation of fenofibrate nanoparticles by combined stirred media milling and ultrasonication method

The production of fenofibrate nanoparticles combining stirred media milling and ultrasonication method was investigated in the current work. The fenofibrate drug sample was first wet milled in stirred media mill for different times and subsequently processed by ultrasonication. The effects of ultrasonication time, power on final product particle sizes were studied. The pre milling by stirred media milling was resulted into reduction of comminution resistance of material. Subsequent treatment by ultrasonication produced smaller particles than obtained by stirred media milling alone. The resulting nanoparticles were found to exhibit excellent stability as investigated by particle size, zeta potential, and multiple light scattering measurement techniques. Further, qualities of nanoparticles obtained by combined approach were characterized by TEM and XRD analysis.     

紫外分光光度法测定非诺贝特片含量的不确定度评定

分析了非诺贝特片含量测定过程中样品的称样量、含量的重复性测量、样品的稀释体积和紫外分光光度法测量吸光度等因素对含量测定不确定度的影响。量化了各分量的相对标准不确定度,进而得出合成标准不确定度和扩展不确定度。建立的不确定度评定方法适用于分光光度法测定非诺贝特片含量的不确定度分析。     

TEBA催化合成非诺贝特酸

在50%氢氧化钾溶液中,4-羟基-4'-氯二苯甲酮(1),氯仿和丙酮在相转移催化剂TEBA的催化下发生缩合反应合成了非诺贝特酸.最佳反应条件为:1 30 g,丙酮120 g,TEBA 2.5 g,氯仿40 g,于30 ℃滴加氯仿,产率89.7%.     

Solvent and salting effects on sample preparation for the determination of fenofibric acid in human plasma by HPLC-DAD

The solvent and salting effects induced on the sample preparation procedure applied to plasma samples containing fenofibric acid and 4-chlorophenyl-4′-hydroxyphenyl methanone (internal standard) are evaluated. Sodium chloride addition during a deproteinization step using both methanol and phosphoric acid influences the recovery of the analytes as well as the selectivity of the process. The chromatographic method allows high sample volume injection (500 μl) with the focusing of both analytes in the stationary phase. The synthesized high porosity octadecylsilica material allows a fast elution gradient at 4 ml/min flow-rate and a complete analysis within 7 min. UV-detection is made at 295 nm and quantitation limit in the 20 ng/ml concentration level can be achieved. The method can be successfully applied for bioequivalence studies on fenofibrate, administrated as prodrug (fenofibric acid represents its main active metabolite) in pharmaceutical formulations. The main parameters used in studying the retention behavior of the internal standard and FEFA were also estimated.     

Effect of Hydrophilic Polymer on Solubilization of Fenofibrate by Cyclodextrin Complexation

The present work investigates the possibility of improvement of the complexation efficiency of cyclodextrin towards a drug by adding a third auxiliary component (hydrophilic polymer). Phase solubility Analysis at 25 °C was used to investigate the interaction of the drug in both the binary systems (viz. Drug-Cyclodextrin and Drug-Polymer) and the ternary system (Drug-Cyclodextrin-Polymer). The combined use of polymer and cyclodextrin was clearly more effective in enhancing the aqueous solubility of the fenofibrate in comparison with the corresponding drug-cyclodextrin or drug-polymer binary systems. Hydrophilic polymers increased the complexation efficacy of cyclodextrin towards fenofibrate (as shown by the increased stability constants of the complexes). Polyvinyl Pyrollidone (PVP) was found to be most effective in enhancing the solubilization of fenofibrate by β-Cyclodextrin, the best results were obtained in ternary system with β-Cyclodextrin in presence of 1%w/v (PVP). Formulated ternary system with optimized drug:cyclodextrin:polymer ratio of 1:3.5:1 w/w resulted in a significant improvement in the dissolution rate of fenofibrate and showed 90% dissolution efficiency (D.E) as compared to around 15% and 83% of the plain drug and binary system respectively. DSC studies was carried out to characterize the ternary complex.