Stable perindopril tert-butylamine salt tablets and preparation method thereof

Abstract

The present invention belongs to the medical technical field and discloses a stable perindopril tert-butylamine salt troche and a preparation method thereof. The perindopril tert-butylamine salt troche mainly consists of 0.1 percent to 10 percent of perindopril tert-butylamine salt, 3 percent to 30 percent of disintegrant, 20 percent to 90 percent of filling agent, 2 percent to 70 percent of stabilizing agent and 0.5 percent to 5 percent of lubricant. The perindopril tert-butylamine salt troche is prepared by a method of adding the disintegrant internally and externally at the same time. The perindopril tert-butylamine salt troche prepared by the present invention can improve the stability of the perindopril tert-butylamine salt obviously and can be used for preparing the medicines for remedying the cardiovascular disease, the hypertension and the heart failure, etc. The preparation method does not have special requirement on equipment and is fit for mass production.

Description

Technical field: [0001] The invention belongs to the technical field of medicine, and relates to a stable perindopril tert-butylamine salt tablet and a preparation method thereof. Background technique: [0002] Perindopril and its salts belong to angiotensin-converting enzyme inhibitors and are widely used in the treatment of cardiovascular diseases, especially in the fields of hypertension and heart failure. Perindopril was first synthesized in the form of sodium salt in US4508729 and EP0049658, but due to its stability problems, EP-A 0308341 and WO 03 / 087050A2 prepared perindopril tert-butylamine salt and arginine respectively salt, which improves the stability of the drug. It is its tert-butylamine salt form that is widely used in the treatment of cardiovascular diseases. Although the stability of tert-butylamine salt is improved compared with sodium salt, the inherent weakness of this type of drug in its structure is still easy to degrade under some relatively harsh co...

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Problems solved by technology

WO2005 / 068490A1 attempts to improve the stability of the preparation by preparing cyclodextrin inclusion complexes of perindopril and its salts, but only briefly introduces the preparation method, and does not clarify whether it has the effect of improving drug stability , the research in WO2007 / 025695A1 shows that the stability of perindopril tert-butylamine salt preparation is closely related to the particle size of the raw material drug. Compared with the drug with large particle size, the drug with small particle size is easier to degrade. Therefore, in order to To improve the stability of the preparation, the author suggests that the average particle size of the raw material drug in the preparation should be above 7 μm. WO20061014-62 A2 reduces the generation of impurity F by adding some alkaline substances with a pH value of 7-14 in the preparation. These Alkaline substances include: sodium bicarbonate, sodium citrate, potassium oxyoxide, etc. Although there is no basis for improving the stability, and there is no data showing the improvement of the stability of the preparation, the patent GB2394660A mentions that there is a large specific surface area Acidic excipients, such as silicon dioxide, can accelerate the degradation of the main drug in the preparation, so there is a certain basis for saying that alkaline substances can inhibit the formation of impurity F

In order to solve the problem of the stability of perindopril in the preparation, many people have done research, but in these studies, some people did not provide conclusive evidence to prove that the stability of the preparation has indeed been improved, and the other part although there are data showing that the preparation The stability of the main drug has been strengthened, but these experiments are limited to the closed environment, and still rely heavily on the packaging. As for the stability of the preparation when it is exposed to the air at high temperature, it has not been discussed.

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