Research Of Fenofibrate Tablets Based On The Nanocrystal Technology

Fenofibrate is a lipid regulator of Chlorine butyric acid.On clinic,it is mainly used in the treatment of hyperlipemia among adult who are not appropriate to the therapy of diet therapy.Furthermore,its curative effect of reducing triglycerides and mixed hyperlipidemia is more obvious to cholesterin’s.Unfortunately,as a Biopharmaceutics Classification System II drug,the absorption and bioavailability of fenofibrate are influenced or limited due to its poor solubility.In this paper,starting from increasing the solubility of the drug,fenofibrate nanocrystals were prepared by drug nanocrystal technology,in order to increase the dissolution,improving the drug absorption and bioavailability.The UV and HPLC methods were established respectively in this paper to analyze the dissolution rate and the content of fenofibrate in vitro.The results showed that the methods were accurate,reliable,stable,and applicable to the quality control of the fenofibrate.Media milling method and high pressure homogenization method were employed to prepared fenofibrate nanocrystals,and the technological conditions of the methods were also studied in this paper with particle size and PI as evaluation index.For media milling method,the process parameters,such as drug concentrations,types and concentrations of stabilizers,machine rotating speed,diameter of grinding beads,amount of grinding beads,grinding time,were investigated via single factor tests.Furthermore,the process conditions were optimized in an orthogonal experiment of four factors and three levels,and the results indicated that the optimized process parameters of media milling method were as follows: the concentration of drug was 150mg/m L,the stabilizer P188 was 15%(to drug amount),the amount of milling pearls(φ=0.5mm)was 35 g,the speed of the ball grinderand was 600r/min,and the time of grind was 7h.For the method of high pressure homogenization,drug concentrations,types and concentrations of stabilizers,pressure of circulating,number of circulating were investigated via single factor tests.Further more,an orthogonal experiment of four factors and three levels was performed.The optimized process parameters of high pressure homogenization method were as follows: the concentration of drug was 8mg/m L,the stabilizer P188 was 10%(to drug amount),the pressure of circulating was 1200 bar,and the number of circulating was 20 times.The pharmaceutical characteristics of fenofibrate nanocrystals were studied,such as their particle size,morphology,crystalline state and dissolution rate,etc.The results indicated that the appearance of self-made nanocrystals was in a blocky irregular as well as the mean particle size was 202 nm with an equally distribution;after Nano-crystallization,the change of crystalline state and chemical structure were not found.Furthermore,compared to bulk drug,solubility of fenofibrate nanocrystals had a significant increase.Dissolution rates showed obvious improvement compared to bulk drug and commercially available tablets.The influences of disintegrating agent,filler and lubricant on properties of fenofibrate nanocrystal tablets were investigated.The optimized prescription ingredients of the tablets were as follows: amount of fenofibrate nanocrystals was equivalent to 100 mg fenofibrate,and pregelatinized starch,PVPP,talcum powder,colloidal silicon dioxide accounted for17.40%,5.0%,1.2%,0.3% of total amount.The characteristics,such as appearance,hardness,breakage,weight variation,disintegration,and dissolution were determined and results suggested that the fenofibrate nanocrystal tablets were of smooth appearance,uniform color,and hardness,breakage,disintegration were all meet the requirements.The content was uniform,quality was stable among batches.In addition,the dissolution was obviously increased with a good reproducibility.