The Development Of Quetiapine Fumarate Sustained Release Tablets

Objective:To develop a chemical preparation of quetiapine fumarate sustained-release tablets,to determine the formulation and process of quetiapine fumarate sustained-release tablets,to study the in vitro release of self-made and reference preparations,to carry out human bioequivalence Test,evaluation of homemade products and reference to the consistency of the preparation.Methods:1.Through the project research,combined with the reverse engineering of the original research to determine the quetiapine fumarate sustained release tablets of the initial prescription,process;2.Study the purchased raw materials,study its crystal form,solubility,particle size,wetting,etc.,to ensure that the raw material drug standards can be carried out the next step of the preparation study;3.Study the original research products,testing the release curve,the relevant substances,to guide the development of self-made products;4.The prescription screening stage of the self-made products,through the reverse engineering analysis and confirm the initial prescription,through the patent query to determine the basic process for the wet granulation,through comparison with the original research,to explore the use of slow release materials and dosage,improve the composition,To study the durability of slow release materials and processes,the prescriptions and processes with high similarity of release curves were obtained by 11 prescriptions at this stage;5.Small test production stage,to self-made products and the original product in vitro release characteristics similar to the production process of each production process parameters,and to verify;6.In the process of enlargement of the pilot,strictly control the process parameters of each production process to ensure that the self-made products and the original research in vitro consistency;7.Human bioequivalence test,the test population using a single dose,self-control two-way cross The in vivo consistency of the quasi-thiepropionate fumarate sustained-release tablets and the reference preparation under fasting and postprandial conditions was investigated.Result:1.Purchased raw materials do not need further treatment,can directly meet the needs of the preparation;2.The best formulation prescription:Quetiapine fumarate:230.26 mg,Microcrystalline cellulose:30 mg,lactose:35 mg,sodium citrate:75 mg,HPMC-K100 LV:155 mg,HPMC-K4M:50 mg,5%HPMC-E5 aqueous solution:q.s.,magnesium stearate:6.0 mg;3.Small test stage of the process:when mixed 5min,the contentis equal to 100.3%,RSD value is 1.00%,5%hydroxypropyl methylcellulose E5 solution is prepared with a speed of 500rpm,the shearing rate 1000rpm,and to grain 1min,Over 20 mesh nylon mesh,the whole process of control of water less than 4%,the total mixed average content of 99.9%,RSD value of 0.56%,compression process control pressure:130-180N,the difference between the weight of±4%,coating weight gain control in 2%to 4%.4.In vitro consistency evaluation:self-made products in different media in the release curve and the original product similarity is greater than 50;5.Pilot enlargement:self-made preparations of the indicators meet the requirements,three batches of self-made products release curve similar to the original research.6.Bioequivalence test:The 90%confidence interval when after meals and the fasting are between 80%to 125%.Conclusion:The preparation of self-made preparations is reasonable;the production process has good reproducibility and stability;the quality of the produced products is controlled,which conforms to the quality standard of quetiapine sustained-release tablets;Self-made products and the original appearance is consistent,in vitro release characteristics are consistent,self-made products are bioequivalence to the original products.