Development Of Clopidogrel Hydrogen Sulfate Tablets

Clopidogrel is one of the commonly used drugs in patients with cardiovascular and cerebrovascular diseases.Since the entry of clopidogrel tablets into the domestic market,its efficacy has been well-recognized and has been praised and relied upon by the majority of patients.However,the patent right of the drug is owned by a foreign company,which results in a relatively expensive drug price,which brings a great economic burden to the drug users.The patent period of clopidogrel is about to expire,which provides opportunities for major domestic pharmaceutical companies to develop similar drugs,and has a broad market prospect.It is believed that in the near future,the successful listing of domestic clopidogrel tablets will break the existing price system and bring good news to patients with cardiovascular and cerebrovascular diseases in China.In this thesis,a quantitative analysis method of clopidogrel hydrogen sulfate was established with the aim of imitation of clopidogrel hydrogen sulfate tablets.The prescription and process of clopidogrel hydrogen sulfate tablets were studied,and laid a foundation for the successful imitation of clopidogrel hydrogen sulfate tablets.In the development of clopidogrel hydrogen sulfate tablets,the quantitative analysis of the drug in the content of the main drug in the tablet and the dissolution test were carried out.The specificity,accuracy,precision,linearity and durability of the analytical method were analyzed.The verification method was established to determine the content of the main drug in clopidogrel hydrogen sulfate by high performance liquid chromatography.The results showed that the excipients in tablets and the related substances produced after forced degradation had no effect on the determination of the main drug.A spectrophotometric method was established to determine the dissolution of clopidogrel bisulfate tablets in hydrochloric acid buffer at pH 2.0.The existence of excipients had no effect on the determination of the main drug content.The specificity,precision,linearity and durability of the analytical methods meet the requirements of quantitative drug analysis.Referring to the prescription of the marketed product,the interaction between the main drug and the auxiliary material is determined to determine that the excipient of clopidogrel sulfate tablets is a binder pregelatinized starch,a filler microcrystalline cellulose and a lactose,a disintegrant cross-linked poly-dimensional Ketone,lubricant magnesium stearate,etc.A prescription study of clopidogrel hydrogen sulfate tablets was carried out,and the formulation was optimized by orthogonal test with hardness,friability and dissolution as parameters.The optimal prescription was determined: clopidogrel hydrogen sulfate 72.12%,lactose 10.34%,gelatinized starch 6.59%,microcrystalline cellulose 4.15%,crospovidone 3.15%(plus),crospovidone 3.15%(Plus),magnesium stearate 0.5%.The study determined the compression process of clopidogrel hydrogen sulfate tablets and conducted a performance study on the compressed tablets.The results showed that the hardness,friability,tablet weight difference,dissolution and other indicators of the compressed tablets met the requirements.A preliminary stability test of clopidogrel hydrogen sulfate tablets was performed.The test results showed that the parameters of the tablet,the main drug content and the dissolution rate did not change significantly after accelerated and long-term tests,and the quality of the pressed tablets was stable.