Preparation method of crystalline clopidogrel bisulfate tablets

Abstract

The invention provides a preparation method of crystalline clopidogrel bisulfate tablets, comprising the following steps of: mixing a medicinal solvent and an inclusion agent with stirring, dissolving by heating to the temperature of 35-90 DEG C, staying cool to room temperature; adding the crystalline clopidogrel bisulfate with uniformly stirring; drying the medicinal solvent by distillation, sieving to obtain clopidogrel bisulfate inclusion particles; uniformly mixing the obtained clopidogrel bisulfate inclusion particles and a pharmaceutic adjuvant at the weight part ratio of 1:0.02-10, followed by tabletting, wherein the addition amount of the inclusion agent is 0.05-0.2 times the weight of clopidogrel bisulfate and the addition amount of the medicinal solvent is 0.5-10 times the weight of clopidogrel bisulfate. According to the clopidogrel bisulfate tablets provided by the invention, the crystal form is not changed; related substances are not increased, the fluidity and compressibility of the raw materials are enhanced, and the stability of the tablets is raised; in addition, the preparation method of the tablets is more suitable for large-scale industrial production.

Description

technical field [0001] The invention belongs to the technical field of pharmaceutical preparations, and relates to a preparation method of crystalline clopidogrel bisulfate tablets. Background technique [0002] Cardiovascular and cerebrovascular thrombosis is a common disease in my country and an important cause of death. Especially in recent years, the incidence of thromboembolic diseases, mainly coronary thrombosis and cerebral thrombosis, is on the rise, seriously endangering human health. [0003] Clopidogrel is a platelet aggregation inhibitor. ATC classification is: B01AC / 04. Clopidogrel also selectively inhibits the binding of adenosine diphosphate (ADP) to its platelet receptor and the activation of the secondary ADP-mediated glycoprotein GPlllb / llla complex, thus inhibiting platelet aggregation. Clopidogrel must Platelet aggregation can be inhibited by biotransformation, but no active metabolite producing this effect has been isolated. In addition to ADP, clopi...

AI Technical Summary

Problems solved by technology

In order to ensure that its related substances will not increase, therefore: the conventional wet granulation tabletting method cannot be used; if the raw material and auxiliary materials are used for direct tableting, it is not feasible to stick the raw material and have cracks; if the dry granulation tabletting method is used, the raw material granules The surface treatment is not complete, and it is better than direct tableting during tableting. There is also the possibility of sticking and splitting, and it increases the processing process, which is not suitable for large-scale production; if hot-melt granulation is used, the main drug is added with other excipients and then mixed with polyethylene Diol 6000 is mixed and heated, and related substances increase; and the main drug and polyethylene glycol 6000 do not infiltrate, the surface of the main drug cannot be treated, and the tablet is still sticky.

Images