Atorvastatin calcium composition, preparation and preparation method thereof

Abstract

The invention relates to a stable atorvastatin calcium composition, a preparation and the preparation method thereof. The atorvastatin calcium preparation is prepared by micronizing active componentsand alkaline auxiliary materials in a prescription, suspending or dissolving into a mixed solvent of methanol and purified water and adopting a spray drying mode; compared with the original research product, the obtained preparation has higher stability, reduces adverse effect and improves the medicine compliance of patients; moreover, the dissolution uniformity is higher, and the bioequivalence test indicates that the product is bioequivalent to the original research product.

Description

technical field [0001] The invention belongs to the technical field of medicine, and in particular relates to a composition, a preparation and a preparation method of atorvastatin calcium. Background technique [0002] Atorvastatin calcium is the third-generation statin blood lipid-regulating drug. It is a selective and competitive inhibitor of HMG-CoA reductase. Acid monoacyl-CoA reductase) and cholesterol synthesis, thereby reducing plasma cholesterol and lipoprotein levels, and by increasing the liver LDL receptors on the cell surface to enhance the uptake and metabolism of LDL. [0003] Atorvastatin calcium can reduce plasma total cholesterol, LDL-C (low-density lipoprotein cholesterol) and Apolipoprotein B can also reduce the levels of very low-density lipoprotein cholesterol and triacylglycerol, and can increase the levels of plasma high-density lipoprotein cholesterol and apolipoprotein to varying degrees. Compared with other lipid-regulating drugs, atorvastatin cal...

AI Technical Summary

Problems solved by technology

This lactone compound does not have any lipid-lowering activity and also causes the well-known myalgia side effects of statins

Especially when excipients are added to make corresponding dosage forms, the contact of statins with excipients will lead to a decrease in the stability of atorvastatin calcium

Calcium carbonate was added to the prescription of the original research product to improve its stability, but in the process of stability investigation, we found that the level of related substances in the original research product increased significantly, indicating that the simple addition of alkaline substance calcium carbonate can improve the potency of atorvastatin calcium. limited stabilizing effect

In addition, it has been reported in the literature that adding a large amount of alkaline substances such as calcium carbonate will react with gastric acid in the body, leading to adverse reactions such as constipation, flatulence, and indigestion.

[0005] Invention patent CN1642526A (WO2003 / 068191) discloses atorvastatin calcium preparations stabilized by basic metal additives. Atorvastatin calcium exists in an amorphous form and is prepared into other forms of preparations after simply mixing with basic metals in the prescription. This preparation process cannot fundamentally solve the problem of atorvastatin calcium instability

However, it does not solve the problem of instability of atorvastatin calcium preparations. In this case, increasing its bioavailability will cause increased side effects of atorvastatin calcium and reduce clinical safety.

[0007] Invention patent CN103690485A discloses oral proliposome containing atorvastatin calcium and its preparation method, and invention patent CN103690513A discloses atorvastatin calcium nano-lipid carrier and its preparation method. Statin calcium liposome improves its stability. The preparation process of this method is relatively complicated, and a large amount of surfactant is used, which increases the irritation to the gastrointestinal tract.

[0008] Invention patents CN104983702A, CN104983690A, CN105030698A, and CN105030728A all disclose a pharmaceutical preparation prepared by using a new crystal form of atorvastatin calcium, which improves the stability of the atorvastatin calcium preparation. It is possible to transform into the existing crystal form, and the probability that the prepared pharmaceutical preparation is not equivalent to the original research product is high, and its safety and effectiveness need to be verified

[0009] Invention patent CN1630510B discloses atorvastatin calcium in pharmaceutical form, its composition and pharmaceutical preparations containing atorvastatin calcium. In the disclosed technical scheme, atorvastatin calcium is micronized and then added to make 900ml The pH of the 0.001M HCl aqueous solution with a pH of about 3 is raised to a pH equal to or greater than the pKa+1 or greater pH-adjusting substance of atorvastatin calcium, and this method can improve the potency of atorvastatin calcium to a certain extent Stability, but a large number of alkaline excipients are added to the prescription, which increases the adverse reactions in the gastrointestinal tract

[0010] In summary, the atorvastatin calcium preparation composition and preparation method reported in existing research reports and patent literature cannot fundamentally solve the problem of atorvastatin calcium stability, and at the same time, there is a large amount of basic auxiliary materials added. The existence of adverse reactions in the gastrointestinal tract

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