Edaravone orally disintegrating tablet and preparation method thereof

Abstract

The invention belongs to the field of pharmaceutical preparations, and provides an edaravone orally disintegrating tablet and a preparation method thereof, the edaravone orally disintegrating tablet contains edaravone, a filler, a disintegrating agent, a flavoring agent and a lubricant, the edaravone orally disintegrating tablet is prepared through a powder direct compression process, and the prepared edaravone orally disintegrating tablet is simple in process, qualified in content and stable in quality.

Description

Technical Field

[0001] The invention belongs to the field of pharmaceutical preparations, and particularly relates to an edaravone orodisintegrating tablet and a preparation method thereof. Background Art

[0002] "Lou Gestational Frost Syndrome" is the common name for "amyotrophic lateral sclerosis (ALS)". ALS is a fatal neurodegenerative disease characterized by progressive degeneration of motor neurons in the brain and spinal cord. The disease is mainly caused by the progressive degeneration of motor neurons, and its course of disease can spread from local to whole body over time: initially, it may be that only the hands cannot hold chopsticks, and then the patient's leg and hand muscles begin to atrophy, and gradually lose the ability to work and take care of themselves. Over time, speech disorders and abnormal digestive tract muscle function may occur, causing difficulty in eating. Finally, the muscles of the respiratory system also begin to atrophy, and patients are very likely to die of respiratory failure. ALS is a relatively small type of motor neuron disease. The international prevalence rate previously calculated is about 4-6 / 100,000. However, China currently does not have very accurate epidemiological survey data on ALS. In 2021, Professor Fan Dongsheng's team at Peking University Third Hospital made a statistical prediction based on the patient's medical insurance data, and estimated the prevalence to be 2.97 / 100,000, that is, there may be nearly 40,000 ALS patients in my country. Although the incidence rate is low, ALS progresses very rapidly. The average survival period of most patients is only 3-5 years, and 90% of patients die within 5 years of onset. The survival rate is even lower than that of cancer, which brings great economic and psychological burdens to families and society. It was once listed as one of the five terminal illnesses by the World Health Organization.

[0003] At present, the cause of ALS is still unclear, and only 5-10% of patients have clear genetic factors. The adult type is autosomal dominant, and the youth type can be autosomal dominant or recessive. Among them, the superoxide dismutase (SOD) mutation located on chromosome 21 is the most common. The other 90%-95% are sporadic cases. For these patients, toxic exposure, viral infection, and autoimmune dysfunction are all known pathogenic factors, but the pathogenesis is still unclear. For a long time, there has been no specific treatment for ALS. Clinically, the treatment of ALS is still mainly to improve the patient's quality of life and delay the progression of the disease, including a series of comprehensive treatment plans such as improving neurological function through drugs, nutritional support, rehabilitation therapy, and psychological support therapy. At present, there are only two drugs approved by the FDA for the treatment of ALS in the world, namely Riluzole and Edaravone. Edaravone, which was launched in 2017, is a free radical scavenger that is believed to alleviate the effects of oxidative stress, which may be a key factor in the onset and progression of ALS. The antioxidant effects of edaravone can provide neuroprotective effects on the nervous system and can potentially slow the progression of the disease.

[0004] Orally disintegrating tablets can quickly disintegrate in the mouth in the absence of water (or with only a small amount of water) and enter the digestive tract with the swallowing action. They are easy to take, quickly absorbed, have high bioavailability, and little irritation to the digestive tract mucosa. They have good compliance for ALS patients. Summary of the invention

[0005] The invention provides an edaravone orodisintegrating tablet and a preparation method thereof. The tablet has stable quality, simple preparation process and is suitable for industrial production.

[0006] The orodisintegrating edaravone tablet of the present invention comprises edaravone, a filler, a disintegrant, a flavoring agent and a lubricant, and is prepared by a powder direct compression process.

[0007] Furthermore, the filler includes but is not limited to one or more of mannitol, lactose, starch, and microcrystalline cellulose; mannitol and microcrystalline cellulose are preferred, wherein mannitol can be purchased from MERCK.

[0008] Furthermore, the disintegrant includes, but is not limited to, one or more of cross-linked carboxymethyl cellulose sodium, low-substituted hydroxypropyl cellulose, pregelatinized starch, and crospovidone; preferably low-substituted hydroxypropyl cellulose and pregelatinized starch, wherein the water-soluble component content of the pregelatinized starch is 15% or less.

[0009] Furthermore, the flavoring agent includes, but is not limited to, one or more of grape flavor, sucralose, and aspartame.

[0010] Further, the lubricant includes an internal lubricant and an external lubricant, including but not limited to magnesium stearate and sodium stearyl fumarate.

[0011] Furthermore, the orodisintegrating edaravone tablet comprises 10-30% edaravone, 50-80% filler, 5-20% disintegrant, 0.15-2.0% flavoring agent, and 0.5-3% lubricant.

[0012] Furthermore, the preparation method of the orodisintegrating tablet of Edaravone is as follows: (1) Edaravone, filler, disintegrant and internal lubricant are mixed uniformly using a three-dimensional mixer; (2) Use Φ7 flat and inclined stamping sheet. Embodiment 1

[0013]

[0014] Preparation process (1) Edaravone, filler, disintegrant and internal lubricant are mixed uniformly using a three-dimensional mixer; (2) Use Φ7 flat and inclined stamping sheet. Embodiment 2

[0015]

[0016] Preparation process (1) Edaravone, filler, disintegrant and internal lubricant are mixed uniformly using a three-dimensional mixer; (2) Use Φ7 flat and inclined stamping sheet. Embodiment 3

[0017]

[0018] Preparation process (1) Edaravone, filler, disintegrant and internal lubricant are mixed uniformly using a three-dimensional mixer; (2) Use Φ7 flat and inclined stamping sheet.

[0019] Comparative Example 1

[0020] Preparation process (1) Edaravone, filler, disintegrant and internal lubricant are mixed uniformly using a three-dimensional mixer; (2) Use Φ7 flat and inclined stamping sheet.

[0021] Comparative Example 2

[0022] Preparation process (1) Edaravone, filler, disintegrant and internal lubricant are mixed uniformly using a three-dimensional mixer; (2) Use Φ7 flat and inclined stamping sheet.

[0023] According to the 2020 edition of the Chinese Pharmacopoeia, the disintegration time limit of the above examples was investigated, and the taste was investigated, and the results were as follows:

[0024] It can be seen from the above test results that Examples 1-3 disintegrate faster and have a good taste; while Comparative Example 1 disintegrates beyond the limit, and Comparative Example 2 disintegrates slightly slower and has a poorer taste.

[0025] The samples prepared in the above example were subjected to dissolution testing in the main medium at pH 4.0 and 75 rpm. The results are as follows:

[0026] It can be seen from the above test results that the dissolution rate of the drugs in Examples 1-3 reached more than 85% in 15 minutes, which is a very rapid dissolution, while the drugs in Comparative Examples 1-2 did not achieve a very rapid dissolution.

[0027] The samples prepared in the above examples were placed at 40°C, RH 75% and 25°C, RH 60% for three months, respectively, to conduct stability tests. The samples were tested for related substances, content and dissolution, and the results were as follows:

[0028]

[0029]

[0030]

[0031] It can be seen from the above test results that the samples of Examples 1-3 are relatively stable, while the related substances of Comparative Example 2 increase significantly under accelerated conditions and the content decreases slightly; the dissolution of Comparative Example 1-2 slows down under accelerated conditions and the stability is poor.

[0032] In summary, the orodisintegrating tablets of edaravone of the present invention have stable process, qualified content and good quality.

[0033] The above embodiments are intended to illustrate the present invention, not to limit the present invention. Any solution that is simply modified from the present invention falls within the protection scope of the present invention.

Claims

1. An orodisintegrating tablet of edaravone and a preparation method thereof, comprising edaravone, a filler, a disintegrant, a flavoring agent, and a lubricant, and is prepared by a powder direct compression process.

2. The orodisintegrating tablet of Edarazide according to claim 1, characterized in that Fillers include, but are not limited to, one or more of mannitol, lactose, starch, and microcrystalline cellulose.

3. The orodisintegrating tablet of Edarazide according to claim 1, characterized in that Disintegrants include, but are not limited to, one or more of croscarmellose sodium, low-substituted hydroxypropyl cellulose, pregelatinized starch, and crospovidone.

4. The orodisintegrating tablet of Edarazide according to claim 1, characterized in that Flavoring agents include, but are not limited to, one or more of grape flavor, sucralose, and aspartame.

5. The orodisintegrating tablet of Edarazide according to claim 1, characterized in that Lubricants include internal lubricants and external lubricants, including but not limited to magnesium stearate and sodium stearyl fumarate.

6. The orodisintegrating tablet of Edaravone according to claim 1, wherein the percentage of the prescription is:

7. The orodisintegrating tablet of Edaravone according to claim 1, wherein the preparation method is as follows: (1) Edaravone, filler, disintegrant and internal lubricant are mixed uniformly using a three-dimensional mixer; (2) Use Φ7 flat and inclined stamping sheet.

8. The orodisintegrating tablet of edaravone according to claims 1-7, wherein the filler may contain 5-10% microcrystalline cellulose or no microcrystalline cellulose.

9. The orodisintegrating tablet of edaravone according to claims 1 to 8, wherein the disintegrant used comprises partially pregelatinized starch having a water-soluble component content of 15% or less, which can be obtained from Colorcon.

10. The orodisintegrating tablet of edaravone according to claims 1-9, wherein the particle size of the raw material is controlled at 10-20 μm.

11. The orodisintegrating tablet of edaravone according to claims 1-10, which has a hardness of 20-45N and can be completely disintegrated within 20-50s.

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