Maleic acid levorotation amlodipine drug active pharmaceutical composition

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The invention provides a maleic acid levorotation amlodipine drug active pharmaceutical composition which comprises the following components: component I: maleic acid levorotation amlodipine; component II: dextrorotation amlodipine; component III: aspartic acid amlodipine; component IV: impurity D; and the active pharmaceutical composition does not contain impurity A, impurity B, impurity C, impurity E, impurity F, impurity G and impurity H basically. The active pharmaceutical composition is stable in quality, and can completely meet the quality requirement of maleic acid levorotation amlodipine preparation on active pharmaceutical composition; and the prepared preparation is safe, effective and controllable in quality, and ensures the clinical effect and medication safety of the maleic acid levorotation amlodipine preparation.

About maleate levamlodipine products, art reported as follows:

Pfizer discloses amlodipine maleate product and its preparation method patent 9 CN0182514, mentioned in the patent: the production of amlodipine maleate product process, especially with amlodipine horse procedure to acid reaction of amlodipine maleate, it is easy to generate impurities amlodipine aspartate (structural formula as shown in Formula 3), by controlling the PH value and the reaction temperature, the reaction system was reduced impurity asparagine conditions amlodipine acid content.

Pfizer discloses compositions containing amlodipine maleate in patent CN01821669. 2, and mentioned in the patent amlodipine maleate product in the preparation and storage of the process, it is easy to generate degradation products day amlodipine aspartate (structural formula as Formula 3) and pyridine analogue of amlodipine (the impurity has been included in the European Pharmacopoeia, referred to impurity D, the same below, the structural formula shown in Equation 4).

The above-mentioned impurities amlodipine maleate product does not fully reflect public maleic acid impurities Levamlodipine products, and its deficiency is that: (I) the above products for amlodipine maleate, is racemate, did impurities in the optical resolution process of the formation of L-body research produced, and therefore can not fully reflect the maleic acid impurities Levamlodipine product composition; (2) only aspartate ammonia chlorine to calm impurity D were studied, no systematic study of other impurities, and therefore unable to determine the composition and content of other impurities affect drug safety.

European Pharmacopoeia discloses amlodipine besylate quality standards, amlodipine besylate may exist in the impurity for impurity A, impurity B, impurity C, impurity D, impurity E, impurity F, impurity G, impurities H et al. However, there may be amlodipine besylate Impurities can not fully reflect the maleate impurities Levamlodipine products.

In summary, the impurities on amlodipine products are disclosed in the prior art does not accurately reflect the maleate Levamlodipine of impurities.

impurity study is a very important element of drug quality study because of adverse drug reactions that occurred in the clinical course and drug use, in addition to the relevant pharmacological activity itself, but sometimes there are impurities contained drugs Large relationship. As we all know, engaged in drug development and drug evaluation is a basic principle to follow is to ensure the safety and effectiveness of marketed drugs, due to stable quality controlled drug is safe and effective medicines to ensure that the premise and foundation, while the impurities research is the quality of medicines an important part of the study, so the study of impurities and impurity control is the key element of drug quality assurance is to ensure that an important manifestation of the effectiveness of drug safety.

Most of the impurities in the drug having potential biological activity, and drug interactions may affect the safety and efficacy of drugs, or even toxic, such as synthetic raw materials remaining in the process, although not yet data show that these impurities give cause direct harm to the human body, but after all, is the drug of “pollutants” and does not have a therapeutic effect, it should be possible to minimize the level, which is an important drug developers to work in line with the countries of the drug development Studies concerning impurities guidelines.

pharmaceutical polymorphs is an important factor in drug stability and bioavailability of influence, through retrieval of existing technology, we can not know maleate levamlodipine product is what the crystal form, but also Stability can not be informed of the existence of this crystal form, and drug stability, uniformity of quality, bioavailability, preparations will have what effect.

Therefore, a systematic study maleate levamlodipine all kinds of impurities in the product composition and crystalline form, the development of suitable methods of preparation, reduce the content of all kinds of impurities maleate levamlodipine products, obtain high-quality products, is to ensure maleate levamlodipine clinical drug safety testing is an important work, improve their quality level API is the key to improving the quality of finished products. So still need improvements to existing technologies, maleate levamlodipine all kinds of impurities in the product research and analysis to determine the specific composition, and its control in a safe, reasonable limits, to obtain high levels of quality and stability maleate levamlodipine.

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