Simvastatin solid composition

Abstract

The invention relates to a simvastatin solid compound, and specifically relates to a method of preparing the simvastatin solid pharmaceutical composition. The composition comprises the following components: simvastatin, citric acid, BHA (Butylated Hydroxyanisole), a diluent, an optional disintegrating agent, an optional adhesive, an optional lubricant and an optical flow aid. The method comprises the following steps: fully mixing crushed simvastatin, citric acid and BHA; and then, fully mixing the mixture with the diluent, the optional disintegrating agent, the optional adhesive, the optional lubricant and the optional flow aid to obtain the solid pharmaceutical composition. The simvastatin solid pharmaceutical composition obtained by the method provided by the invention has excellent pharmaceutical properties.

Description

technical field [0001] The invention relates to a solid pharmaceutical composition and a preparation method thereof, in particular to a stable simvastatin solid composition and a preparation method thereof. Background technique [0002] Simvastatin was developed by Merck of the United States. It is an HMG-CoA reductase inhibitor semi-synthesized from lovastatin. Medications for episodic hypercholesterolemia. Simvastatin is a fat-soluble substance. It can be rapidly absorbed after oral administration, reaching the peak blood concentration within 1-2 hours, with a half-life of 2-4 hours, and its 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. [0003] Because of its good lipid-lowering effect and definite curative effect, simvastatin has always been a key imitation product of domestic pharmace...

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Problems solved by technology

[0003] 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

[0004] 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 research 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 proposed is that in this patent, a large amount of acid-causing agent (10%) and antioxidant (0.8% ), as a medicine 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 medicine 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

[0005] 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

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