Stability Indicating Liquid Chromatographic Method for the Determination of Fenofibrate and its Application to Kinetic Studies

Abstract

A stability-indicating LC assay method was developed for the quantitative determination of fenofibrate (FFB) in pharmaceutical dosage form in the presence of its degradation products and kinetic determinations were evaluated in acidic, alkaline and peroxide degradation conditions. Chromatographic separation was achieved by use of Zorbax C18 column (250 × 4.0 mm, 5 μm). The mobile phase was established by mixing phosphate buffer (pH adjusted 3 with phosphoric acid) and acetonitrile (30:70 v/v). FFB degraded in acidic, alkaline and hydrogen peroxide conditions, while it was more stable in thermal and photolytic conditions. The described method was linear over a range of 1.0-500 μg/ml for determination of FFB (r= 0.9999). The precision was demonstrated by relative standard deviation (RSD) of intra-day (RSD= 0.56– 0.91) and inter-day studies (RSD= 1.47). The mean recovery was found to be 100.01%. The acid and alkaline degradations of FFB in 1M HCl and 1M NaOH solutions showed an apparent zero-order kinetics with rate constants 0.0736 and 0.0698 min−1 respectively and the peroxide degradation with 5% H2O2 demonstrated an apparent first-order kinetics with rate constant k = 0.0202 per min. The t1/2, t90 values are also determined for all the kinetic studies. The developed method was found to be simple, specific, robust, linear, precise, and accurate for the determination of FFB in pharmaceutical formulations.

Confined crystallization of fenofibrate in nanoporous silica

“…38 Fenofibrate has an estimated molecular size of 0.98-1.27 nm. 34 It is hypothesized that this is the reason why the 12 nm CPG showed no crystalline fenofibrate in the powder X-ray diffraction results, as it is less than 20 times the diameter of fenofibrate. Ha et al found an similar size limit to crystalline versus amorphous stability in porous matrices, noting that crystallization of the compound ROY was supressed in 20 nm pores as compared to 30 nm pores when carried out either by evaporation or by melting/cooling.…”

“…Enough sample of API-loaded CPG was added such that the targeted concentration of fenofibrate in solution was 15 μg mL −1 , within the expected linear range. 34 Samples of both uncrushed and crushed bulk fenofibrate were analyzed as comparison. Samples were acquired for about 29 hours.…”