Fenofibrate Osmotic Pump Tablets Preparation Process, Quality Standard And Pharmacokinetic Study

Fenofibrate is a fibric acid derivative that functions as a hypolipidemic agent. In this paper, fenofibrate was selected as a model drug to prepare mono-layer osmotic pump tablets (MOPT). Based on the quality study of the product, quality control standard was set up. Then, pharmacokinetic study of mono-layer osmotic pump tablets was performed in three dogs·1. Preparation process researchIn the preparation of fenofibrate MOPT, polyethylene oxide(PEO) and sodium chloride were used as the tablet core. Cellulose acetate(CA) and polyethylene glyeol4000(PEG 4000) were selected as the coating materials and acetone was employed as the coating medium. According to drug release mechanism of MOPT, formulation of tablet core, coating membrane, preparation of tablet core and the condition of drug release were investigated to discuss the effects of different kind of factors on the release behavior of MOPT. Similarity factors was used as the evaluation standard. Based on single-factor experiments, the synthetical mark was used as the evaluation standard to optimize the formulations according to orthogonal experiment design.The results indicated that the optimal formulation had the excellent zero-order release character and reproducibility of different batches. The mechanism of the drug release was discussed simply.2. Quality standard researchThe quality control of fenofibrate MOPT was researched. According to character of fenofibrate and feature of MOPT, a HPLC method was setup for related substances and relative content of it. ultraviolet spectrophotometry methods were established for dissolution.Each method was exact sensitive,had good selectivity and reproducibility while the excipients and decomposition products could be well separated from fenofibrate.These showed that the analytical methods were reasonable and practical, the quality was controllable.3. Pharmacokinetic study on fenofibric acid in dog plasmaWith the commercial common fenofibrate tablet as the reference, the pharmacokinetics study and relative bioavailability of self-prepared fenofibrate MOPT was performed in three dogs by using HPLC for determining fenofibric acid. The AUC of reference tablets(100 mg) and fenofibrate MOPT(150 mg) are 145.17±20.61 and 169.55±6.90μg·h·mL-1 respectively.The Cmax and Tmax of reference tablets are7.65±0.42μg-mL-1 and 4.3±0.6 h.The Cmax and Tmax of fenofibrate MOPT are 5.64±0.37μg·mL-1 and 10.7±1.2 h.The relative bioavailability of fenofibric acid was 123.07±5.41%.The two formulations are bioequivalent according to the results of analysis of variance.Fenofibrate MOPT has good correlation between absorption in vivo and drug release in vitro.