The Time-controlled Design And Mechanisim Invastigation Of Rupturable Pulsatile Capsules

In this study,the pulsatile coated capsules with designed lagtime was prepared and evaluated in vitro.Further more,the burst mechanism was researched and FEM models were established to provide guidance for study of pulsatile coated capsules.The content of metoprolol tartrate(MT)and Nifedipine(NF)were derermined by ultraviolet and visible spetrophotometry(UV-VIS).Good linear relationship of MT between concentration and absorbance was found at the range of 20.1?g/mL~161.0?g/mL(A=0.00404C+0.00501,r=0.9999).Good linear relationship of NF between concentration and absorbance was found at the range of 20.13?g/mL~161.04?g/mL(A=0.0149C–0.0048,r=0.9999).And the precision and recovery were acceptable for further study.Pulsatile capsules were prepared by dip-coating method.The lag time was investigated to select coating level,types and content of disintegrant.It was found that the optimized disintegrant was L-HPC of25%,coating level was 4 layers.The optimized lag time was 6.5±0.5 h which agreed with clinical requirements.The drug content is 98.8%of the labeled amount that met the requirements of content uniformity.The durg release before coating burst was less than 1%and after burst was more than 85%of within 2 hours.Swelling pressure of capsules was determined using a self-made device.Swelling pressure determination method was established to discuss the influence factors.It was showed that types of filler,types and content of disintegrant significantly affected the swelling pressure.While types and amount of drug had insignificant influence.The water uptake behavior of pulsatile capsules was studied by means of time sampling and weighing.Coating level had significant impact on water uptake,however,the content of swelling agent had little influence.The results of swelling pressure and water uptake behavior could be used in the late mechanism study.Free film was prepared by dip-coating process.Mechanical properties of the film were measured by tensile test.The brittle character of EC film was identified with low tensile strength at break(?_b=1.68±0.27 MPa),low strain at break(?_b=2.5±0.18%),high elastic modulus(E_t=52.9±6.1 MPa)and low Poisson's ratio(?=0.25±0.08).Geometry models of coatings were built using FEM software(ANSYS10.0).The swelling pressure and material properties were applied to the models for simulation.Prediction equation of lag time was established finally.The results of simulation of coating burst behavior and prediction of lag time well agreed with the experiment results.