Stable simvastatin oral tablet and preparation method thereof

Abstract

The invention provides a stable simvastatin oral tablet which is prepared from the following components in percentage by weight: 10-20% of simvastatin, 0.01-0.04% of antioxidant, 0.5-2.0% of acidifier, 70-80% of filler, 5-10% of disintegrant, 1-1.2% of lubricant and 0.5-2% of binder. The invention also provides a method for preparing the stable simvastatin oral tablet. By strictly controlling the moisture of a finished product, the doses of the antioxidant and acidifier in the components are obviously reduced, the product stability is better, and the safety is higher.

Description

A kind of stable simvastatin oral tablet and preparation method thereof technical field The invention relates to a medicine tablet and a preparation method thereof, in particular to a stable simvastatin oral tablet and a preparation method thereof. Background technique Simvastatin was developed by Merck of the United States. It is an HMG-CoA reductase inhibitor semi-synthesized from lovastatin. Drugs for episodic hypercholesterolemia. Simvastatin is a fat-soluble substance. It can be rapidly absorbed after oral administration, reaching the peak blood concentration within 1 to 2 hours, and the half-life is 2 to 4 hours. The activity in the body is 4 times that of pravastatin, which can effectively prevent the development of atherosclerosis and heart disease recurrence. Reduce the risk of nonfatal myocardial infarction and myocardial revascularization. Because of its good lipid-lowering effect and definite curative effect, simvastatin has always been a key imitation prod...

AI Technical Summary

Problems solved by technology

Because of its good lipid-lowering effect and definite curative effect, simvastatin has always been a key imitation product of domestic pharmaceutical manufacturers. At present, there are more than 170 domestic approval numbers, and the competition is fierce. However, due to the poor stability of simvastatin, it cannot The content will drop sharply under high temperature and high humidity environment, which requires high preparation technology, so there are few varieties that are actually on the market in China, and even for the varieties that have been on the market, the quality of various manufacturers is also uneven

At present, the stability of simvastatin is mainly solved by adding antioxidants and acid-causing agents to obtain satisfactory results. For example, in the instructions of the original manufacturer, it is clearly proposed to add butylated hydroxyanisole as an antioxidant, and at the same time add citric acid and vitamin c Synergistic effect to improve the effect of antioxidant, but the specific dosage is not mentioned in the specification; for example, in the patent CN1977841A applied by Shanghai Xinyi Vientiane Pharmaceutical Co., Ltd., it is proposed to add 0.05-0.1% antioxidant, but it needs to be mentioned This patent uses the direct tableting process. As far as the domestic pharmaceutical industry is concerned, the direct tableting process still has technical problems such as unstable tablet weight, sticking, and unsuitable coating during the tableting process. Large-scale Production is very difficult; as mentioned in the authorized patent CN1994296B of Zhejiang Jingxin Pharmaceutical Co., Ltd., by adding an acidic pH regulator, the pH value of the aqueous solution of the pharmaceutical preparation is in the range of 2.5-3.2, which is the same as that of antioxidants. The combined application of other auxiliary materials can effectively inhibit the oxidation process of simvastatin. What needs to be mentioned is that in this patent, in order to achieve the effect of stabilizing simvastatin, a large amount of acidogen (10%) and antioxidant (0.8% ), as a drug that needs to be taken for a long time, adding a large amount of acid-causing agents will definitely stimulate the gastrointestinal tract to secrete too much gastric juice, increase the burden on the gastrointestinal tract, and cause discomfort to the patient, while antioxidants in food and drugs The range of use is strictly controlled. For example, the FDA limits the concentration of BHA in food to no more than <0.2%. This is because BHA has a possible carcinogenic risk in a large number of animal experiments. The amount of acidogens and antioxidants used in the prescription is very beneficial to the safety of the product

As a consensus in the pharmaceutical industry, the water content of the finished preparation has a greater impact on the stability of the drug, especially for drugs whose degradation pathway is dominated by hydrolysis reactions. For example, the water content of ampicillin sodium must be controlled below 1%. The stability decreases significantly with the increase of