Tablets containing clopidogrel hydrogen sulfate and preparation method thereof

Abstract

The invention belongs to the field of pharmaceutical preparations. For the defects that sticking of a clopidogrel hydrogen sulfate material exists and tablets prepared from the clopidogrel hydrogen sulfate material are prone to hydrolysis in the storage process, a method for preparing non-sticking clopidogrel hydrogen sulfate intermediate particles is discovered, the clopidogrel hydrogen sulfate intermediate particles are further prepared into tablets, and the tablets are good in formability and can be continuously compressed without sticking. The tablets are simple in preparation method, can be produced by adopting a conventional preparation method without special equipment, has the significant advantages of being easy to industrialize, high in production efficiency, good in stability, controllable in quality and the like and has the outstanding substantive feature and the significant improvement.

Description

technical field [0001] The invention relates to the field of pharmaceutical preparations, in particular to a tablet containing clopidogrel bisulfate and a preparation method thereof. Background technique [0002] The chemical name of clopidogrel hydrogen sulfate is S(+)-2-(2-chlorophenyl)-2-(4,5,6,7-tetrahydrothieno[3,2-c]pyridine-5) Methyl acetate bisulfate, an inducible platelet aggregation inhibitor, acts by inhibiting the binding of adenosine monophosphate to its receptor. By inhibiting platelet aggregation, it reduces the chance of arterial blockage, achieves the effect of preventing stroke and heart attack, and can effectively treat and prevent atherosclerosis. [0003] It has been reported in the literature that clopidogrel bisulfate tablets are easily degraded into clopidogrel acid during storage, especially when exposed to moisture, or when they coexist with magnesium stearate, polyvinylpyrrolidone and colloid. Therefore, in order to improve its stability and bioa...

AI Technical Summary

Problems solved by technology

The dextroisomer of clopidogrel is its active form, but in practice, it is found that the dextroisomer of clopidogrel is unstable and easily converted into an inactive or even toxic levoisomer, which has great potential for safety in clinical use. big impact

In addition, practice has also found that due to the inherent characteristics of clopidogrel bisulfate itself, it is easy to stick to the tablet during the tablet compression process. Using magnesium stearate as a lubricant is the most effective excipient to solve the sticky punch, but stearic acid Magnesium can cause the degradation of clopidogrel bisulfate. When other lubricants are used to replace magnesium stearate, sticking and flushing are prone to occur during the preparation process, which affects the quality and yield of the preparation

[0004] Chinese patent (Application No. CN201410324788.1) discloses clopidogrel bisulfate tablets and its preparation method. The patent uses the auxiliary material mannitol as a complexing agent to play the role of anti-oxidant synergism and prevent the conversion of dextro isomers; At the same time, polyethylene glycol is used as a lubricant to add to the granules containing clopidogrel bisulfate. This method of adding lubricant is difficult to solve the problem of sticking and punching in the long-term tableting process of this product.

This high humidity and high heat granulation and drying method is likely to cause the degradation of clopidogrel bisulfate

[0008] The purpose of the present invention is to provide a tablet containing clopidogrel bisulfate and a preparation method thereof, which can ensure that the clopidogrel bisulfate tablet remains stable during preparation and storage, and reduce the conversion into levoisomer or degradation into The risk of clopidogrel acid; at the same time, it also solves the problem of sticking and punching during the preparation process and improves production efficiency

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