Study Of Imatinib Mesylate Loaded In Hollow Mesoporous Silica Nanoparticles As Carriers System And Analytical Method

Imatinib Mesylate(IMM)as an anticancer drug was often used to Philadelphia positive chronic myeloid leukemia,chronic myeloid leukemia(CML)in blast crisis,gastrointestinal stromal tumors(GISTs)and some other diseases.The drug was developed by the Swedish company novartis.As anti-cancer drugs,we hope that it could slowly and lasting effect on the human body.At present,the dosage forms of IMM mainly tablets and capsules,the effect of sustained release can not be obtained.Hollow mesoporous silica nanoparticles(HMSNs)which have the combination of both mesoporous structure and hollow structure,have a wide range of applications in the biomedical field.They have high surface areas,tunable pore sizes with narrow distributions,well-defined surface properties,low toxicity and very good biocompatibility,are suitable to control the release of drugs and targeted transport.So our study researched the synthesis of HMSNs loaded with IMM,and the release way,in order to achieve sustained release purposes.HMSNs was synthesized by self-template method with solid SiO2 nanoparticles as template.The prescription process of synthesis of hollow mesoporous silica spheres was studied.The influence of different etching time and temperature on the removal of template was discussed.The structure of synthesized sample was investigated with Transmission Electron Microscope,Elemental Analysis;then,the drug delivery performance of HMSNs was studied,IMM was choosen as the model drug,studied the drug-loading and drug-release performance.The results showed that the organized HMSNs with good sphericity,uniform size and big drug-loading ability could be synthesized.At attention,in the 48 h,the cumulative release rate of the drug was about 60 percent,reaching the purpose of sustained release.Eventually,a stability indicating UPLC/Q-TOF-ESI-MS/MS method has been developed for the simultaneous determination of IMM and its impurity and degradation products in the active pharmaceutical ingredient(API)and drug products.Gradient elution of 0.1% g/mL Ammonium formate buffer at pH 8.57 and acetonitrile were used as the mobile phase and Waters Acquity UPLC CSH C18,100 mm×2.1 mm,1.7 μm particle size column was utilized as stationary phase.Quality by Design(QbD)principle which belongs to the forefront in the international pharmaceutical field wasapplied to the method development approach and the chromatography modeling software—DryLab?2000 plus and Design Expert?8.0.6 were used to optimize the chromatographic method.The result showed that baseline separation of all peaks of all components could be achieved and the resolution of 2.0 could be reached in all experiments.The UPLC method was validated for specificity,linearity,accuracy,precision and robustness in compliance to the ICH guideline Q2(R1).The method we developed was a fast,robust and reliable UPLC method with higher suitability and specificity.Furthermore,elemental composition and major fragments of all components were characterized through the optimized UPLC/Q-TOF-MS/MS analysis.