Preparation And Evaluation Of Metoprolol Tartrate Sustained Release Pellets

In this study,the effect of formulation and process parameters on the compatibility,plasticizing efficiency and operating performance of HME?hot melt extrusion?was investigated.MT?metoprolol tartrate?sustained release pellets were prepared based on optimized formulation and process parameters.In vitro and in vivo release of MT sustained release pellets was evaluated.Melting point and degradation temperature of MT and EC were determined using melting point instrument and TGA.The result indicated that HME operating temperature should be set at the range of 100¹80?.MT content determination method was established.Good linear relationship between concentration and absorbance was found at the range of 9.9?g/mL¹49.1?g/mL?A=0.00417+0.00794 C,r=0.9991?,and the precision and recovery met the requirements.In vitro dissolution method was established.Free film and extrudate containing different plasticizers were prepared.The solubility parameter,the appearance of free film and the drug content of extrudate were investigated to evaluate the HME compatibility.Good compatibility was found between MT,EC and most of the plasticizers,while the drug cotent in the extrudate containing DBS was the best.The mechanical properties of free film were measured using tensile test to evaluate the plasticizing efficiency.It was found that DBS could effectively improve the extensibility and reduce the mechanical strength of free film.HME torque was used as an index to investigate the influence of plasticizer types,plasticizer content,extrusion temperature and mixing time on operating performance.It was found that plasticizer types had little influence on operating performance.And the optimized plasticizer content was 20%,extrusion temperature was 110?,and mixing time was 10 min.MT cores were prepared by HME,and MT sustained release pellets were prepared by HMC.The influence of pore-foaming agents and coating level on drug content and in vitro drug release was investigated.It was found that types and content of pore-foaming agents had significant influence on MT content and release,whereas coating level had little influence.The optimized formulation was investicated by DSC?differential scanning calorimetry?and SEM?scanning electron microscope?,and the results indicated that MT dispersed in the form of amorphous form and coating corrosion was taken place during the dissolution.The in vitro release behavior and mechanism was studied.It was found that the release mechanism of cores and sustained release pellets was mainly diffusion and combination of diffusion and corrosion,respectively.In vivo MT content determination method was established.Good linear relationship between concentration and peak area was found at the range of 9.9?g/mL¹49.1?g/mL?A=20.831C+2.781,r=0.9998?.Precision and recovery met the requirements.Using MT solution as the control group,the pharmacokinetics of MT sustained pellets was studied.The results indicated that MT sustained release pellets had lower and longer-term blood drug concentration compared with MT solution(C_maxax was decreased from 13.8?g/mL to 6.9?g/mL,while T_maxax was prolonged from 0.5 h to 4.0 h).Bioavailability of MT sustained pellets close to MT solution?the relative bioavailability was 125.4%?.