Preparation Of Rivaroxaban Solid Dispersion And Its Capsules

Rivaroxaban was a highly efficient selective Xa factor inhibitor developed by Bayer and Johnson,which was mainly used to prevent venous thromboembolism after hip or knee replacement surgery.Rivaroxaban belongs to BCS II drugs,which was characterized by water solubility and high intestinal permeability.In order to improve its solubility and dissolution rate,in this paper,the preparation of solid dispersions to improve the drug solubility and dissolution rate in water,with PEG6000,PVP k30 and coPVP as the carrier.Respectively,using solvent method,melting method and solvent melt preparation of rivaroxaban solid dispersion,and on the basis of solid dispersions prepared capsules.The research contents of this paper are as follows:1.The preformulation study of rivaroxaban solid dispersionAccording to the physical and chemical properties of rivaroxaban and the preparation technology of solid dispersions,investigated the solubility of rivaroxaban in different solvents;Established content determination of rivaroxaban,dissolution determination of solid dispersions,dissolution determination and UV-Vis analysis in vitro of rivaroxaban capsule.2.The preparation study of rivaroxaban solid dispersion:In this paper,the PEG6000,PVP k30 and coPVP as the carrier.Using the solvent method,melting method and solvent melting method to prepare solid dispersions.Based on the dissolution of SD in dissolution medium,studying the influence of carrier type,preparation method,drug carrier ratio,experiment time,experiment temperature on the solid dispersions of dissolution and determines the best preparation process: the quality ratio of rivaroxaban to coPVP was 1:10,the solvent method was chosen as the preparation method,acetic acid as solvent,reaction time was 45 min and reaction temperature was 65 oC.3.The quality standard study of rivaroxaban solid dispersion:The solid dispersions were identified by differential scanning calorimeter,X-ray powder diffraction and scanning electron microscopy.The results showed that rivaroxaban existed in the form of crystallization in the physical mixture,while in the solid dispersion,rivaroxaban existed in the amorphous state,which provided a basis for improving the dissolution of the drug.In addition,this paper studied the influence of high temperature,high humidity,strong illumination,accelerated test,long-term test on content and dissolution of solid dispersions,which showed that rivaroxaban solid dispersion should be stored under low temperature,dry,sealed conditions.4.Preparation technology and quality evaluation of rivaroxaban solid dispersion capsule:A single factor method was used to investigate the selection of fillers,disintegrating agents and lubricants in the preparation of rivaroxaban solid dispersion capsules.After the experiment,3 factors of selecting filler ratio,disintegrating agent ratio and lubricant ratio,3 levels of each factor.Based on the dissolution of drugs in dissolution medium,using the method of orthogonal test analysis to optimize the prescription process of rivaroxaban solid dispersion capsule,and obtaining optimal prescription and technology of rivaroxaban solid dispersion capsule.The optimized prescription is: choosing filler selected pregelatinized starch,disintegrating agent selected carboxymethyl starch sodiumh,lubricant selected sodium salt,after using the method of direct powder filling capsule,self-made capsules and commercially available rivaroxaban tablets have similar dissolution rate.