Research On The Preparation Of Nimodipine Solid Dispersions By Spray Congealing

The solid dispersion can make the poorly soluble drugs highly dispersed in the carrier to improve the drug dissolution rate thus enhancing oral absorption and bioavailability,so it attracts widespread attention.Melting method without the use of organic solvents,safety and no pollution,is one of the common method for preparation of solid dispersion.But there are some drawbacks,such as the cooling rate is too slow and difficult to smash and so on.To this end,this paper explores the feasibility of the solid dispersinon prepared by spray congealing with model drug of nimodipine to overcome the above deficiencies,so that it can increase drug dissolution to achieve better bioavailability.First of all,we investigate the stability and solubility of nimodipine in different media to determine the dissolution medium of acetate buffer with 0.075%SDS.In this paper,UV spectrophotometry is carried out for the drug content and dissolution of nimodipine solid dispersion.It found the drug's concentrations have a good linear relationship with the absorbance at 238nm.The sufficient recovery is 101.7%,the RSD of intraday and interday precision are lower than 2%.The high performance liquid chromatography is carried out for the nimodipine content and related substances in the stability tests.The method has good linearity and good accuracy.The sufficient recovery is 100.5%.The RSD of intraday and interday precision are lower than 2%.All the results are accurate and reliable.Secondly,we study the formulation and process of nimodipine solid dispersion prepared by spray congealing.Using dissolution in vitro of nimodipine as index,we investigate the type and dosage of carrier material,surfactants,condensing temperature,feed temperature,atomization pressure to determine the formulation and optimal conditions:polyethylene glycol 6000(PEG6000)is the carrier material,the proportion of nimodipine and PEG6000 is 1:5,Tween 80 is a surface active agent,the condensation temperature should not be more than 20 ?,atomization pressure of 0.4 MPa.Dissolution in vitro of solid dispersion is 90%in 60 min,significantly higher than 10%dissolution of API.The results of X-ray powder diffraction,differential scanning calorimetry and scanning electron microscopy indicated that the drug in the solid dispersion is amorphous state with microcrystalline.Preliminary stability tests showed that the solid dispersions remain stable at room temperature for 3 months.Finaly we have the pharmacokinetic studies in rats to research the vivo absorption of solid dispersion.High performance liquid chromatography is carried out to establish an analysis method in vivo for pharmacokinetic studies,the extraction recovery of the biological samples is 96.11%.The method has good linearity and good accuracy.The sufficient recovery is 110.3%.The RSD of intraday and interday precision are lower than 10%.All the results are accurate and reliable.The rats are randomly divided into three groups,oral administration of homemade nimodipine solid dispersion,commercial formulation nimotop,physical mixtures of nimodipine and polyethylene glycol.Take blood from the canthus of rats at each time points and process the samples by protein deposition method with methanol.The drug concentrations are determined by high performance liquid chromatography.The dates are statistical by DAS and SPSS.The results show that solid dispersion formulations has a good bioavailability which is 107.1%to the reference,450.5%to the physical mixture.Its compartment model fitting comply with a compartment model.