Preparation And Quality Study Of Felodipine Sustained Release Table

Objective:Felodipine is a calcium channel blocker,used widely in the treatment of hypertension.Because it is classified to BSC II with high permeability and low solubility,increasing release rate plays a significant role in bioavailability.In this paper,utilizing the micronation technology and surfactants,the hydrophilic gel matrix(materials hydroxypropyl methylcellulose?HPMC?and hydroxypropyl cellulose?HPC?were used to prepare felodipine sustained-release tablets to stabilize blood concentration,reduce the administrative frequency and improve patient compliance.Methods:1.The content,release rate and oxide product of felodipine sustained-release tablets were determined by HPLC and methodological verification was carried out.2.The type and amount were preliminarily determined by solubility of felodipine API.Through the analysis of reference preparation,key quality attributes and release conditions were confirmed.3.The effects of solubilization method,type and amount of sustained-release materials on the release rate and related quality attributes were investigated by single-factor experiment.4.Further,formulation was optimized by orthogonal experiment,which was used in amplification and verification of prescription process.The influcing factor experiment was conducted during 10 days.The release rate in different release media of self-made felodipine sustained-release tablets and reference preparation was evaluated by f₂?similarity factor?and the release mechanism of felodipine was analyzed by Korsmeyer-Peppas equation.Results:1.The determination method of content,release and oxide of felodipine sustained-release tablets was established,and its methodological verification was carried out,which had good specificity,linearity,accuracy and precision.2.Felodipine had good linear relationship in release media with different concentrations of Tween 80and it can meet the trough-condition under various pH conditions when the Tween 80content is 0.1%.Studying on the key quality attributes of the reference preparation,development target and the basic formulation were determined,and it was found that the standards of each pharmacy were not discriminative.Finally,0.1%Tween 80 was confirmed as release medium.3.After micronization of the felodipine API,it was dispersed in polyoxyethylene-40 hydrogenated castor oil,resulting to better solubilization.When HPC was added outside and HPMC?E10M?and HPMC?E50?were added inside,the obtained soft material can meet the requirements and have no over-viscosity problem.The hardness and burst-release of the sustained-release tablet was also significantly improved and inhibited,respectively.The types of HPC had a great impact on drug release.The HPC?HXF?and HPC?GXF?with high viscosity can slow down significantly drug release,and HPC?EXF?with low viscosity can fasten release.Finally,HPC?JXF?with moderate viscosity was selected,and the amount of HPC?JXF?,HPMC?E50?and HPMC?E10M?was screened by orthogonal experiment.The optimal prescription was:25mg HPMC?E10M?,40mg HPMC?E50?and 50mg HPC?JXF?.The release rate of self-made felodipine tablets were more similar to the reference preparation`s.The release rates of the three batches of amplified batches showed good repeatability of the formulation and process was conducted to obtain the preservation condition.4.The release rate of self-made felodipine sustained-release tablets and reference preparation in different release media was higher than 50,which was considered as the criterion of similar dissolution.The dose-dumping reuslts showed that changes of relaese were similar.And the Korsmeyer-Peppas equation showed that the release mechanism was skeleton corrosion.The influcing factor experiment showed that felodipine sustained-release tablet keep stable under high temperature,high humidity and hard light.Conclusion:The release behavior of felodipine sustained-release tablets prepared using sustained-release matrix materials HPMC and HPC can be consistent with the reference preparation by micronization technology and surfactant addition,and the key quality attributes can keep stable.