Study On Preparation Technology And Consistency Evaluation Of Olanzapine Tablets

Olanzapine is a second-generation atypical antipsychotic drug developed by Eli Lilly in the 1980s.It interacts with 5-HT receptors and dopamine receptors,α₁ receptor,H₁ receptor and M receptor.It is mainly used to treat schizophrenia and moderate to severe manic episodes,with low side effects and high safety.It is also used to prevent the recurrence of bipolar disorder.In this study,we selected the same excipients as ZYPREXA to develop Olanzapine tablets.Through the screening and optimization of the formulation and process,as well as the pilot scale-up production,the formulation process was finally determined.The prescription is（in 1000tablets）:Olanzapine 5.0g,lactose 137.6g,microcrystalline cellulose 38.4g,hydroxypropylcellulose 10.0g,crospovidone 7.0g,magnesium stearate2.0g,Opadry^?13B180000 16.0g,and purified water 133.3g.By investigating the key factors that affect the dissolution of the preparation,it is determined that the most suitable particle size range D90 of the bulk drug is 26-47μm,which has not been reported in the literature.Afterwards,quality research was carried out.HPLC inspection methods for content determination,related substances,dissolution rate and dissolution curve were established.Methodological verification was carried out,and the quality standard of Olanzapine tablets was established.According to the determined prescription process,3 batches were continuously pilot-produced in the preparation GMP workshop with a batch of 200,000 tablets.All quality indicators of the products meet the requirements,indicating that the determined prescription process is stable and feasible.Through a comprehensive comparative study with ZYPREXA,the related substances are equivalent to ZYPREXA.The dissolution behavior in four different medium is similar to that of ZYPREXA,which meets the quality consistency evaluation requirements of generic drugs.Through the stability test and the quality comparison with ZYPREXA,the results show that the quality indicators and stability of Olanzapine tablets are basically the same as those of ZYPREXA.The prescription process is reasonable,and the quality of the prepared product is reliable.A random,open,double-cycle,double-crossover design is adopted for fasting administration.The absorption rate and degree of self-made olanzapine tablets（5mg,test preparation）and ZYPREXA（5mg,reference preparation）are equivalent,indicating that the self-made olanzapine tablets are bioequivalent to ZYPREXA.