Levocarnitine tablet and preparation method thereof
By using a combination of polyvinylpyrrolidine, mixed microcrystalline cellulose and lubricant in levocarnitine tablets, and using secondary tableting and modified microcrystalline cellulose, the problem of poor hygroscopic resistance in the tablet form is solved, achieving a more stable and uniform tablet effect.
Patent Information
- Application Number
- CN202311612032.2
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2023-11-29
- Publication Date
- 2025-05-30
AI Technical Summary
L-carnitine tablets are difficult to maintain hygroscopic resistance in the form of tablets, resulting in stability and flavor problems.
The anti-hygroscopicity of the tablet is improved by the use of secondary tableting and modified microcrystalline cellulose using a combination of levocarnitine or its derivatives, polyvinylpyrrolidine, mixed microcrystalline cellulose.
It significantly improves the anti-hygroscopic ability of levocarnitine tablets, ensures the stability and uniformity of the tablets, and improves the tablet pressing effect.
Abstract
Description
Technical Field
[0001] The present invention belongs to the technical field of pharmaceutical preparations, and particularly relates to a levocarnitine tablet and a preparation method thereof. Background Art
[0002] Levocarnitine or its derivatives or its pharmaceutically acceptable salts, whose main function is to promote lipid metabolism. During hypoxia and ischemia, acyl-CoA accumulates, and long-chain acylcarnitine in mitochondria also accumulates. Free carnitine decreases due to a large amount of consumption, and ischemia and hypoxia lead to cell death. In addition, during hypoxia, anaerobic glycolysis of glucose is the main process, and the accumulation of fatty acids and others leads to acidosis, ion disorder, and cell autolysis and death. A sufficient amount of free carnitine can enable the accumulated acyl-CoA to enter mitochondria, reduce its inhibition of adenine nucleotide translocase, and enable oxidative phosphorylation to proceed smoothly.
[0003] This product combines levocarnitine or its derivatives or its pharmaceutically acceptable salts and trimetazidine hydrochloride or its derivatives or its pharmaceutically acceptable salts into a compound drug. It combines the promotion of fatty acid oxidation by levocarnitine or its derivatives or its pharmaceutically acceptable salts and the promotion of sugar oxidative energy production by trimetazidine or its derivatives or its pharmaceutically acceptable salts through compound compatibility, and through the optimization of dose combination, a compound levocarnitine tablet is developed, enabling this preparation to play an excellent anti-hypoxia role in preventing tissue hypoxia.
[0004] Developing levocarnitine or its derivatives or its pharmaceutically acceptable salts and trimetazidine or its derivatives or its pharmaceutically acceptable salts into an oral solution preparation has problems of stability and flavor correction. However, if developed into an oral tablet, there are also problems that it is very difficult to mix the mixture of levocarnitine or its derivatives or its pharmaceutically acceptable salts and trimetazidine or its derivatives or its pharmaceutically acceptable salts evenly by conventional mixing methods and that levocarnitine or its derivatives or its pharmaceutically acceptable salts are extremely hygroscopic. In order to overcome the above difficulties, there is an urgent need to develop a tablet with better anti-hygroscopicity. Summary of the Invention
[0005] In view of the above technical problems, the present invention provides a levocarnitine tablet with good moisture resistance.
[0006] One object of the present invention is to provide a levocarnitine tablet, which includes the active ingredient levocarnitine or its derivatives or its pharmaceutically acceptable salts, polyvinylpyrrolidone, mixed microcrystalline cellulose, and a lubricant. The levocarnitine tablet after mixed tableting has remarkable moisture absorption resistance.
[0007] Preferably, the levocarnitine tablet, by mass fraction, includes 80 - 100 parts of the active ingredient levocarnitine or its derivatives or its pharmaceutically acceptable salts, 10 - 15 parts of polyvinylpyrrolidone, 30 - 45 parts of mixed microcrystalline cellulose, and 1 - 5 parts of a lubricant.
[0008] Preferably, the mixed microcrystalline cellulose is composed of microcrystalline cellulose and modified microcrystalline cellulose mixed in a mass ratio of 10:1 to 3.
[0009] Preferably, the preparation method of the modified microcrystalline cellulose is as follows: Mix a sulfuric acid solution with a mass fraction of 50% and microcrystalline cellulose at a solid-liquid ratio of mL / g of 10:1, maintain the temperature at 45 - 50°C, perform ultrasonic oscillation, filter, wash with water, dry, soak the dried product in water, then add methyltrimethoxysilane accounting for 20 - 30% of the mass of the dried product, stir evenly, carry out static reaction at 50 - 60°C, filter, wash with ethanol, and dry to obtain the modified microcrystalline cellulose.
[0010] Preferably, the levocarnitine or its derivative or its pharmaceutically acceptable salt is selected from levocarnitine, acetyllevocarnitine, propionyllevocarnitine and their pharmaceutically acceptable salts.
[0011] Preferably, the lubricant is selected from one or more of magnesium stearate and talcum powder.
[0012] Another object of the present invention is to provide a preparation method of levocarnitine tablets. The preparation method is as follows: By mass, it includes 80 - 100 parts of the active ingredient levocarnitine or its derivative or its pharmaceutically acceptable salt, 10 - 15 parts of polyvinylpyrrolidone, 30 - 45 parts of mixed microcrystalline cellulose, and 1 - 5 parts of lubricant. Mix them to obtain a premix, press the premix at 5 kN / cm, remove it, put it into a pulverizer, control the air humidity inside the pulverizer to be 70%, pulverize and then screen through a 20-mesh sieve for granulation, and press at 10 kN / cm to obtain levocarnitine tablets. Beneficial effects
[0013] In the present invention, the modified cellulose in the mixed microcrystalline cellulose can effectively resist moisture on the surface, and at the same time, by using secondary tableting, the uniformity of the main drug content and the tableting effect can be better. Specific embodiments
[0014] The following further illustrates the present invention in conjunction with embodiments. The embodiments are helpful for better understanding the present invention, but the present invention is not limited to the following embodiments only.
[0015] Preparation method of modified microcrystalline cellulose: Mix a sulfuric acid solution with a mass fraction of 50% and microcrystalline cellulose at a solid-liquid ratio of mL / g of 10:1, maintain the temperature at 45 - 50°C, perform ultrasonic oscillation for 40 min, filter, wash with water, dry, soak the dried product in water, then add methyltrimethoxysilane accounting for 20 - 30% of the mass of the dried product, stir evenly, carry out static reaction at 50 - 60°C for 2 h, filter, wash with ethanol, and dry to obtain the modified microcrystalline cellulose.
[0016] The mixed microcrystalline cellulose is composed of microcrystalline cellulose and modified microcrystalline cellulose mixed in a mass ratio of 10:1 to 3. Example 1
[0017] Components of levocarnitine tablets: 80 parts of levocarnitine; 10 parts of polyvinylpyrrolidone; 30 parts of mixed microcrystalline cellulose; 1 part of magnesium stearate. Example 2
[0018] Components of levocarnitine tablets: 90 parts of levocarnitine; 12 parts of polyvinylpyrrolidone; 38 parts of mixed microcrystalline cellulose; 3 parts of magnesium stearate. Example 3
[0019] Components of levocarnitine tablets: 100 parts of levocarnitine; 15 parts of polyvinylpyrrolidone; 45 parts of mixed microcrystalline cellulose; 5 parts of magnesium stearate.
[0020] Comparative Example 1 Components of levocarnitine tablets: 90 parts of levocarnitine; 12 parts of polyvinylpyrrolidone; 38 parts of microcrystalline cellulose; 3 parts of magnesium stearate.
[0021] Examples 4 to 7 The raw materials in Examples 1 - 3 and Comparative Example 1 were respectively mixed to obtain a premix. The premix was tabletted at 5 kN / cm, removed, put into a pulverizer, and the air humidity inside the pulverizer was controlled at 70%. After pulverization, it was sieved through a 20 - mesh sieve for granulation and then tabletted at 10 kN / cm to obtain levocarnitine tablets.
[0022] Examples 8 to 11 It is basically the same as Examples 4 to 7, and the only difference is that tabletting is directly carried out at 10 kN / cm to obtain levocarnitine tablets.
[0023] Detection was carried out in accordance with the Pharmacopoeia of the People's Republic of China (2020 Edition). The effect of Example 5 was the best. The effects of Examples 4 - 6 and 8 - 10 were better than those of Example 7, and the effect of Example 7 was better than that of Example 11.
[0024] After the preferred embodiments of the detailed description, those skilled in the art can clearly understand that various changes and modifications can be made without departing from the scope and spirit of the above-mentioned patent application. Any simple modifications, equivalent changes, and modifications made to the above embodiments based on the technical essence of the present invention all belong to the scope of the technical solution of the present invention. Moreover, the present invention is not limited by the implementation manners of the examples given in the specification.
Claims
1. A levocarnitine tablet, characterized in that, the tablet comprises an active ingredient of levocarnitine or its derivatives or its pharmaceutically acceptable salts, polyvinylpyrrolidone, mixed microcrystalline cellulose, and a lubricant.
2. The levocarnitine tablet according to claim 1, characterized in that, the levocarnitine tablet, by mass parts, comprises 80 - 100 parts of an active ingredient of levocarnitine or its derivatives or its pharmaceutically acceptable salts, 10 - 15 parts of polyvinylpyrrolidone, 30 - 45 parts of mixed microcrystalline cellulose, and 1 - 5 parts of a lubricant.
3. The levocarnitine tablet according to claim 2, characterized in that, the mixed microcrystalline cellulose is composed of microcrystalline cellulose and modified microcrystalline cellulose mixed in a mass ratio of 10:1 - 3.
4. The levocarnitine tablet according to claim 3, characterized in that, the preparation method of the modified microcrystalline cellulose is to mix a sulfuric acid solution with a mass fraction of 50% and microcrystalline cellulose in a solid-liquid ratio of mL / g of 10:1, keep the temperature at 45 - 50°C, perform ultrasonic oscillation, filter, wash with water, dry, soak the dried product in water, then add 20 - 30% of methyltrimethoxysilane based on the mass of the dried product, stir evenly, stand and react at 50 - 60°C, filter, wash with ethanol, and dry to obtain the modified microcrystalline cellulose.
5. The levocarnitine tablet according to claim 2, characterized in that, the levocarnitine or its derivatives or its pharmaceutically acceptable salts are selected from levocarnitine, acetyllevocarnitine, propionyllevocarnitine, and their pharmaceutically acceptable salts.
6. The levocarnitine tablet according to claim 2, characterized in that, the lubricant is selected from one or more of magnesium stearate and talcum powder.
7. The preparation method of the levocarnitine tablet according to any one of claims 1 - 6, characterized in that, the preparation method is as follows: by mass parts, it includes 80 - 100 parts of an active ingredient of levocarnitine or its derivatives or its pharmaceutically acceptable salts, 10 - 15 parts of polyvinylpyrrolidone, 30 - 45 parts of mixed microcrystalline cellulose, and 1 - 5 parts of a lubricant. Mix them to obtain a premix, press the premix at 5 kN / cm, remove it, put it into a pulverizer, control the air humidity inside the pulverizer to be 70%, pulverize and then screen through a 20 - mesh sieve for granulation, and press at 10 kN / cm to obtain the levocarnitine tablet.