Preparation Of Sirolimus Nano-tablets

Since the beginning of the 21st century,all types of organ transplants have been carried out in major centers in China,and immune rejection has become a common problem that plagues organ transplant doctors.Sirolimus(Rapamycin,SRL)as a new and efficient third-generation immunosuppressive agent is an immunosuppressive agent that has been discovered so far with low toxicity and potential for immense use.However,sirolimus is poor in water solubility and low in dissolution,which makes it difficult to be absorbed by the body and has low bioavailability.Drug nanoization is an important way to solve the problem of low bioavailability of poorly water-soluble drugs.Therefore,in this paper,sirolimus nanoparticles were prepared using a variety of reactors and the sirolimus tablet formulation was optimized.The main contents and innovations of the full text are as follows:(1)Nano sirolimus drug particles were prepared by anti-solvent recrystallization in a conventional stirred reactor(STR).The effects of solvent type,type and amount of stabilizer,volume ratio of anti-solvent/solvent(AS/S),drying method on the drug particles were investigated.Under good conditions,spherical sirolimus nano-drug particles with an average particle size of about 110 nm can be obtained.(2)The spherical sirolimus nano drug particles with an average diameter of 80-270 nm and well dispersed were prepared by using a microchannel reactor.The influence of the microstructure parameters and the process parameters of the microchannel reactor on the preparation of sirolimus nanoparticles was investigated.It was found that the smaller the microchannel dimension,the longer the mixed length,the smaller the prepared drug particles.Moreover,the micro-mixing efficiency of the T-type microchannel is better than that of the Y-type microchannel reactor,and the nanometer drug particles are prepared with smaller particle size.(3)Using a high-gravity rotating bed combined with anti-solvent recrystallization method,spherical sirolimus nano-particles with an average particle diameter of about 240 nm and a good dispersion were prepared under high-concentration conditions,which greatly shortened the recrystallization time of the system and improved the yield,achieve 0.13kg/h,suitable for continuous industrial production.Nanoparticles were prepared by spray-drying the nanosuspension.The drug particles have good dispersion,regular morphology and particle size.The dissolution rate and dissolution rate were greatly increased.The dissolution rate was up to 90%in 10min,while the bulk drug dissolved only 3%over the same period.The powder has good stability,and the structure,crystal form,and particle size remain unchanged after storage for 110 days at room temperature.The result of FT-IR analysis showed that the structure and composition of sirolimus nanoparticles were the same as those of the drug substance;XRD test showed that the crystallinity of sirolimus was reduced after nanocrystallization,and appeared in the amorphous form in the nanoparticles.(4)The formulation of sirolimus nano-tablets was optimized,and the effects of composition,content and compression pressure on tablet performance and dissolution were examined.Each performance index of self-made tablet products meets the requirements of pharmacopoeia,and the dissolution rate is similar to the dissolution curve of commercially available sirolimus tablets.The drug dissolution can reach about 70%in two hours,ensuring the same clinical bioequivalence.