| The MCM-41 Type Mesoporous silica nanospheres(MSNs)and Santa Barbara Amorphous-15(SBA-15)are two kinds of mesoporous silica(MS),which were prepared via the modified templating method,were used to solidify the SRL-SMEDDS that was prepared by our previous research group.The adsorption ability of MS was then investigated.The self-made SRL-SMEDDS-MS was capsuled,and its in vitro,in vivo properties were investigated to compare with commercial tablet Rapamune?.The High-performance liquid chromatography method(HPLC)was established to measure the SRL in vivo.The method for measuring the SRL has strong specificity,high sensitivity,meet the needs of SRL preparation quality control.The MSNs was prepared via hexadecyl trimethyl ammonium bromide(CTAB)used as template and ethylsilicate(TEOS)used as silicon source under alkaline conditions;the polyethylene oxide–polypropylene oxide–polyethylene oxide(P123)and TEOS were used as template and silicon source respectively to prepare SBA-15 under acidic condition.The reaction temperature was changed to prepare SBA-15 in different pore size.Scanning electron microscope reveals the sphere-like and rod-like shape of MSNs and SBA-15,respectively.The internal channel structure could be observed under transmission electron microscope.The surface area and pore size of MSNs and SBA-15 were calculated via BET and BJH model,which were 1007.67 m2·g-1 and 2.7nm for MSNs,and the surface area were 578.51 m2·g-1,410.2 m2·g-1,554.67 m2·g-1 and pore size were 6.3 nm,8.1 nm,10.8 nm for SBA-15.The stirring method was used to prepare SRL-SMEDDS-MS.It was found that the optimal ratio of SRL-SMEDDS to MSNs and SRL-SMEDDS to different pore size of SBA-15 were 2.0:1 and 1.5:1 respectively.Under this ratio,the flow properties and resuspension experiment showed good results,and the pore size of SBA-15 made little influence on the adsoption ability of SBA-15.The self-made SRL-SMEDDS-MSNs and three different kinds of SRL-SMEDDS-SBA-15 were capsuled to test the in vitro dissolution properties.When compared with commercial tablet Rapamune?,thecumulative drug release rate of SRL-SMEDDS-MS was improved with the dissolution media were 0.4% SDS solution and distilled water.The cumulative drug release rate of SRL-SMEDDS-MSNs in water and 0.4% SDS solution within 2 h were 82% and 95%,respectively,which were higher then the cumulative drug release rate of three different kinds of SRL-SMEDDS-SBA-15 in water and 0.4% SDS solution,which were 70% and79%,respectively.It was also found that the maxium drug release rate of three different kinds of SRL-SMEDDS-SBA-15 are similar,while the larger the pore size was,the more obvious burst release to be observed.Liquid-liquid extraction and Liquid chromatography-tandem mass spectrometry(LC-MS/MS)methods were developed for the whole blood sample treatment and SRL blood concentration determination in beagle dogs with Ascomycin(FK520)as internal standard and tert-Butyl methyl ether as extract solvent.The study of analytical methodology proved little influence were made on the determination of the result by the impurity in plasma.It showed good linear relationship under various weights when the drug concentration was 0.5~32 ng·mL-1,and the correlation index was above 0.999.The result of recovery,repeatability and stability were all in good condition.The in vivo bioavailability of commercial tablet Rapamune?,self-made capsuled SRL-SMEDDS-MSNs and capsuled SRL-SMEDDS-SBA-15 were investigated in beagle dogs.It was found that when compared with commercial tablet Rapamune?,the relative bioavailability of SRL-SMEDDS-MSNs and SRL-SMEDDS-SBA-15 were173.67% and 120.57%,respectively. |
PDF Full Text Request