Olpicopone orally disintegrating tablet and preparation method thereof

Abstract

The invention belongs to the technical field of pharmaceutical preparations, and particularly relates to an olpilapone orally disintegrating tablet and a preparation method thereof. The invention provides an olpicobond orally disintegrating tablet which comprises the following components in percentage by weight: 5.0%-30.0% of olpicobond, 55.0%-75.0% of a water-soluble filler, 0.5%-3.0% of hydrophobic silicon dioxide, 4.0%-11.0% of a disintegrating agent and 0.9%-2.0% of a coating material, wherein the density of the water-soluble filler is not less than 0.5 g / ml. The olpilapone orally disintegrating tablet provided by the invention not only can be rapidly disintegrated in the oral cavity, but also can be stably placed, is convenient to take, does not need to be taken with water, has good compliance, and is easy to realize industrial development.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of pharmaceutical preparations, and particularly relates to a orally disintegrating tablet of opicapone and a preparation method thereof. BACKGROUND

[0002] Parkinson's disease (PD) is a common chronic neurodegenerative disease, and the incidence rate is increasing with age. With the progression of the disease, the motor and non-motor symptoms of Parkinson's disease will gradually worsen, and PD patients have a long course of disease and need long-term drug treatment. Drug treatment usually first chooses compound levodopa treatment, and when the symptoms worsen and the efficacy decreases, dopamine receptor agonists (DAs), monoamine oxidase type B inhibitors (MAO-BI) or catechol-O-methyltransferase inhibitors can be added.

[0003] Opicapone is a third-generation catechol-O-methyltransferase (COMT) inhibitor with strong and persistent COMT inhibitory activity, which can reduce the metabolism of levodopa and allow more levodopa to enter the brain, thereby better exerting the drug efficacy and helping to improve the motor symptom control of Parkinson's (PD) patients.

[0004] Epidemiological investigation of Parkinson's disease shows that the average onset age of PD disease is about 60 years old, and elderly patients often have poor medication compliance due to swallowing disorders, which further affects their treatment effect and quality of life. The existing dosage form of opicapone is a solid tablet and hard capsule. However, opicapone is almost insoluble in water, and has problems such as photosensitivity, poor flowability and poor stability, which are not conducive to commercial process development. SUMMARY

[0005] In view of this, the application provides an orally disintegrating tablet of opicapone and a preparation method thereof. The orally disintegrating tablet can not only disintegrate rapidly in the oral cavity, but also can be stably placed, is easy to take without the need for water, has good compliance, and is easy to realize industrialization development.

[0006] To solve the above technical problems, the application provides an orally disintegrating tablet of opicapone, which comprises, according to the weight ratio, 5.0%-30.0% of opicapone, 55.0%-75.0% of a water-soluble filler, 0.5%-3.0% of hydrophobic silicon dioxide, 4.0%-11.0% of a disintegrant, and 0.9%-2.0% of a coating material; wherein the water-soluble filler is a high-density water-soluble filler with a density of ≥0.5g / ml.

[0007] The high-density water-soluble filler is selected for granulation, which can make the granules and raw materials fully mixed and bonded, and obtain granules with small volume and large density. The high-density water-soluble filler has good water solubility and does not affect the drug dissolution; when the coating weight is the same, the coating layer of smaller granules is thicker, which is beneficial to enhance the light shielding effect and reduce impurities; in addition, the high-density water-soluble filler can obtain granules with small volume and large density, and under the same tablet weight and hardness, the orodispersible tablets with thinner thickness can be obtained, and under the same tablet weight and thickness, the orodispersible tablets with lower hardness can be obtained; when the orodispersible tablets are taken without water, saliva can enter the tablet core more quickly, thereby accelerating the disintegration rate in the oral cavity. In addition, the orodispersible tablets provided by the application also add hydrophobic silicon dioxide, thereby more effectively blocking the entry of external moisture, and ensuring that the orodispersible tablets can be stably stored in a high-temperature and high-humidity environment.

[0008] Preferably, the proportion of the opicapone is 10.0%-20.0%.

[0009] Preferably, the proportion of the hydrophobic silicon dioxide is 1.0%-1.5%.

[0010] In combination with the first aspect, the thickness of the opicapone orodispersible tablet is ≤3.0 mm, and the average hardness is 5.0-8.0 kN.

[0011] In combination with the first aspect, the high-density water-soluble filler is selected from at least one of mannitol, lactose, sorbitol and maltitol; and the disintegrant is selected from at least one of cross-linked polyvinylpyrrolidone (PVPP), sodium carboxymethyl starch (CMS-Na), low-substituted hydroxypropyl methyl cellulose (L-HPC) and cross-linked sodium carboxymethyl cellulose (CCNa). In combination with the first aspect, the coating material is a water-soluble coating material, and is selected from at least one of hydroxypropyl methyl cellulose (HPMC), hydroxypropyl cellulose (HPC) and polyvinyl alcohol (PVA).

[0012] In combination with the first aspect, according to the proportion by weight, the opicapone orodispersible tablet further comprises a binder 2.5%-3.0%, a flavoring agent 2.5%-5.0% and a lubricant 0.8%-1.2%.

[0013] In combination with the first aspect, the binder is selected from at least one of starch, dextrin, polyvinylpyrrolidone (PVP), copolymerone, hydroxypropyl cellulose (HPC) and hydroxypropyl methyl cellulose (HPMC); the flavoring agent is selected from at least one of xylitol, aspartame, sucralose, neotame, banana flavor, pineapple flavor, orange flavor, orange flavor, mint flavor and strawberry flavor; and the lubricant is selected from at least one of magnesium stearate, calcium stearate, glycerol monostearate, sodium stearyl fumarate and talc.

[0014] The application further provides a preparation method of the opicapone orally disintegrating tablet, and the steps comprise: The raw drug opicapone, water-soluble filler, adhesive and disintegrating agent are granulated and dried to obtain opicapone granules; The coating material is dissolved in water, and then the coating is performed through bottom spraying of a fluidized bed to obtain coated granules; The coated granules are mixed with hydrophobic silicon dioxide, flavoring agent, lubricant and disintegrating agent, and then tableted to obtain the opicapone orally disintegrating tablet.

[0015] In combination with the second aspect, the granulation process is wet granulation, extrusion-spheronization granulation or fluidized bed one-step granulation.

[0016] In combination with the second aspect, the particle size of the opicapone granules is 200-800 μm, and the bulk density is greater than or equal to 0.5 g / ml.

[0017] In combination with the second aspect, the coating weight gain of the granules is 0.3%-3.0% during coating.

[0018] Preferably, the coating weight gain of the granules is 0.5%-1.5% during coating.

[0019] The application develops an opicapone orally disintegrating tablet according to the characteristics that the PD patients are mostly middle-aged and old people and the physicochemical properties of the raw drug, and the beneficial effects of the application compared with the prior art are as follows: The application uses water-soluble granule coating to realize light-proof of the raw drug without affecting the dissolution of the preparation; the addition of hydrophobic silicon dioxide makes the opicapone orally disintegrating tablet have good stability, is not easy to absorb moisture during storage, maintains good hardness, and does not affect the disintegration performance; in addition, by controlling the bulk density of the granules, a tablet with small tablet thickness under the same tablet weight is prepared, so that when the orally disintegrating tablet is taken without water, saliva can easily enter the tablet core, so that the orally disintegrating tablet is rapidly disintegrated and takes effect. DETAILED DESCRIPTION

[0020] In order to make the purpose, technical scheme and advantages of the application clearer and more apparent, the application will be further described in detail below in combination with specific embodiments. It should be understood that the specific embodiments described herein are only used to explain the application and do not limit the application.

[0021] Those skilled in the art can understand that unless otherwise defined, all terms (including technical and scientific terms) used herein have the same meaning as commonly understood by those skilled in the art to which the application belongs. It should also be understood that terms such as those defined in general dictionaries should be understood as having meanings consistent with those in the prior art, and unless specifically defined, should not be interpreted as having idealized or overly formal meanings.

[0022] The raw material of opicapone is light unstable, the capsule and the tablet have shell and coating film to avoid light respectively, and the orally disintegrating tablet is non-coated tablet, so there is a risk of increasing impurities caused by light degradation. Moreover, the orally disintegrating tablet is easy to absorb moisture, thereby reducing the hardness and affecting the product quality.

[0023] The present application aims at the poor light stability of opicapone and the requirement of rapid disintegration and storage stability of the orally disintegrating tablet, selects high-density water-soluble filler and suitable disintegrant for granulation, performs granule coating with water-soluble coating material, and then presses the tablet after adding hydrophobic silicon dioxide, so that the granule performance of opicapone is improved, and an orally disintegrating tablet of opicapone with rapid disintegration and good stability is obtained.

[0024] The raw material reagents and equipment used in the present application are all conventional commercially available ordinary reagents and ordinary equipment unless otherwise specified.

[0025] Example 1 The present embodiment provides an orally disintegrating tablet of opicapone, and the components and contents are shown in Table 1, and the preparation steps include: The prescription amount of the internal added raw and auxiliary materials opicapone, water-soluble filler and disintegrant is added into a wet granulator, and pre-mixed for 3 minutes after starting stirring and cutting, the binder and appropriate amount of water are added after pre-mixing is completed, and soft material is prepared by stirring and cutting for 5 minutes, and the granulation is performed by passing through a 24-mesh sieve, and the drying is performed in a fluidized bed at 60 DEG C until the moisture content is less than or equal to 1.0%, and the whole granulation is obtained by sieving with a 24-mesh sieve.

[0026] The whole granulation is added into a fluidized bed, the fan is started, and the granulation is heated to be in a good fluidized state, the coating material aqueous solution is sprayed into the fluidized bed, and the coating is performed at 40-50 DEG C until the weight gain is 0.5%-1.0%, and the coated granulation is obtained.

[0027] The coated granulation, the additional auxiliary material hydrophobic silicon dioxide, the flavoring agent, the lubricant and the disintegrant are added into a mixer for total mixing, and the tablet is pressed after the total mixing is completed, and the orally disintegrating tablet of opicapone is obtained.

[0028] Example 2 The present embodiment provides an orally disintegrating tablet of opicapone, and the components and contents are shown in Table 1, and the preparation steps include: The prescription amount of the internal added raw and auxiliary materials opicapone, water-soluble filler and disintegrant is added into a wet granulator, and pre-mixed for 3 minutes after starting stirring and cutting, the binder and appropriate amount of water are added after pre-mixing is completed, and soft material is prepared by stirring and cutting for 5 minutes, and the granulation is performed by passing through a 24-mesh sieve, and the drying is performed in a fluidized bed at 60 DEG C until the moisture content is less than or equal to 1.0%, and the whole granulation is obtained by sieving with a 24-mesh sieve.

[0029] The whole granulation is added into a fluidized bed, the fan is started, and the granulation is heated to be in a good fluidized state, the coating material aqueous solution is sprayed into the fluidized bed, and the coating is performed at 40-50 DEG C until the weight gain is 0.5%-1.0%, and the coated granulation is obtained.

[0030] The coated granules are added with the extra excipients hydrophobic silicon dioxide, flavoring agent, lubricant and disintegrant into a mixer for general mixing. After completion, the tablets are pressed to obtain the orally disintegrating tablets of opicapone.

[0031] Comparative Example 1 This comparative example provides an orally disintegrating tablet of opicapone, the components and contents of which are shown in Table 1, and the preparation steps are similar to those of Example 1, which will not be repeated here.

[0032] Comparative Example 2 This comparative example provides an orally disintegrating tablet of opicapone, the components and contents of which are shown in Table 1, and the preparation steps are similar to those of Example 1, which will not be repeated here.

[0033] Table 1 Prescription composition of Examples 1-2 and Comparative Examples 1-2

[0034] Example 3 This example provides an orally disintegrating tablet of opicapone, the components and contents of which are shown in Table 2, and the preparation steps include: The prescription amount of the internal excipients opicapone, water-soluble filler, disintegrant and binder are added into a wet granulator, pre-mixed for 2 minutes with stirring and cutting, and then an appropriate amount of water is added, and the soft material is prepared by stirring and cutting for 3 minutes. The granules are obtained by extrusion and rolling for 5-10 minutes using a 2.0 mm screen, with a rotating speed of 200 r / min and a drying temperature of 60°C until the water content is less than or equal to 1.0%. The opicapone granules are obtained by sieving with a 20 mesh screen.

[0035] The granules are added into a fluidized bed, and the fan is turned on and heated to make the granules in a good fluidized state. The coating material solution is sprayed into the fluidized bed, and the coating is performed at a temperature of 40-50°C until the weight gain is 1.0%-2.0%. The coated granules are obtained.

[0036] The coated granules are added with the extra excipients hydrophobic silicon dioxide, flavoring agent, lubricant and disintegrant into a mixer for general mixing. After completion, the tablets are pressed to obtain the orally disintegrating tablets of opicapone.

[0037] Comparative Example 3 This comparative example provides an orally disintegrating tablet of opicapone, the components and contents of which are shown in Table 2, and the preparation steps are similar to those of Example 3, which will not be repeated here.

[0038] Comparative Example 4 This comparative example provides an orally disintegrating tablet of opicapone, the components and contents of which are shown in Table 2, and the preparation steps are similar to those of Example 3, with the only difference being that the opicapone granules are not coated, and the remaining steps are the same, which will not be repeated here.

[0039] Table 2 Prescription composition of Examples 3 and Comparative Examples 3-4

[0040] Example 4 The present example provides a oral disintegrating tablet of opicapone, the components and contents of which are shown in Table 3, and the preparation steps include: The prescription amount of the internal added raw and auxiliary materials opicapone, water-soluble filler and disintegrant are added into a wet granulator, pre-mixed for 3 minutes with stirring and cutting, then the binder and appropriate amount of water are added, and the soft material is prepared by stirring and cutting for 5 minutes, and then granulated by passing through a 24-mesh sieve, and the granules are dried in a fluidized bed at 60°C until the moisture content is less than or equal to 1.0%, and then the granules are sieved by a 24-mesh sieve to obtain opicapone granules.

[0041] The granules are added into a fluidized bed, the fan is turned on, and heated to make the granules in a good fluidized state, and then the coating material aqueous solution is sprayed into the fluidized bed, and coated at 40-60°C until the weight gain is 0.5-1.0%, to obtain coated granules.

[0042] The coated granules and the externally added auxiliary materials hydrophobic silicon dioxide, flavoring agent, lubricant and disintegrant are added into a mixer for total mixing, and then the tablet is pressed to obtain an oral disintegrating tablet of opicapone.

[0043] Comparative Example 5 The present comparative example provides an oral disintegrating tablet of opicapone, the components and contents of which are shown in Table 3, and the preparation steps are similar to those of Example 4, which will not be repeated here.

[0044] Comparative Example 6 The present comparative example provides an oral disintegrating tablet of opicapone, the components and contents of which are shown in Table 3, and the preparation steps are similar to those of Example 4, which will not be repeated here.

[0045] Table 3 Prescription composition of Example 4 and Comparative Examples 5-6

[0046] Example 5 The present example provides an oral disintegrating tablet of opicapone, the components and contents of which are shown in Table 4, and the preparation steps include: The prescription amount of the internal added raw and auxiliary materials opicapone, water-soluble filler and disintegrant are added into a wet granulator, pre-mixed for 3 minutes with stirring and cutting, then the binder and appropriate amount of water are added, and the soft material is prepared by stirring and cutting for 3 minutes, and then granulated by passing through a 24-mesh sieve, and the granules are dried in a fluidized bed at 60°C until the moisture content is less than or equal to 1.0%, and then the granules are sieved by a 24-mesh sieve to obtain opicapone granules.

[0047] The granules are added into a fluidized bed, the fan is turned on, and heated to make the granules in a good fluidized state, and then the coating material aqueous solution is sprayed into the fluidized bed, and coated at 40-60°C until the weight gain is 0.5-1.0%, to obtain coated granules.

[0048] The coated granules were added with hydrophobic silicon dioxide, flavoring agent, lubricant and disintegrant into a mixer for total mixing, and then tableted to obtain the oripavil oral disintegration tablet (tablet thickness 2.6 mm).

[0049] Example 6 This example provides an oripavil oral disintegration tablet, the components and contents of which are shown in Table 4, and the preparation steps are similar to those of Example 5, except that the thickness of the tablet is 2.2 mm.

[0050] Comparative Example 7 This comparative example provides an oripavil oral disintegration tablet, the components and contents of which are shown in Table 4, and the preparation steps are similar to those of Example 5, except that the thickness of the tablet is 3.3 mm.

[0051] Comparative Example 8 This comparative example provides an oripavil oral disintegration tablet, the components and contents of which are shown in Table 4, and the preparation steps are similar to those of Example 5, except that the thickness of the tablet is 3.7 mm.

[0052] Table 4 Formulation composition of Examples 5-6 and Comparative Examples 7-8

[0053] Test Example 1 The bulk density and particle size of the oripavil whole granules obtained in Examples 1-2 and Comparative Examples 1-2 were tested, and the average hardness, disintegration time and average tablet thickness of the obtained oripavil oral disintegration tablets were determined, and the determination methods and results are shown in Table 5.

[0054] Table 5

[0055] As can be seen from Table 5, the bulk density of the whole granules prepared in Examples 1-2 using high-density water-soluble filler as an excipient is greater, and the particle size is smaller. In the case of the same tablet thickness, the average hardness of the oripavil oral disintegration tablets obtained in Examples 1-2 is significantly lower than that of Comparative Examples 1-2, and the disintegration time is significantly faster. For the same tablet weight, the greater the density of the total mixed granules, the smaller the tablet forming pressure required for the same tablet type, and therefore the hardness is lower and the disintegration is faster.

[0056] Test Example 2 The oripavil oral disintegration tablets prepared in Examples 1-3 and Comparative Examples 3-4 were subjected to accelerated experiment, related substance determination and dissolution test, wherein: (1) Accelerated experiment conditions: The oripavil oral disintegration tablets prepared in Examples 1-3 and Comparative Examples 3-4 were placed in a stability test box with a temperature of 40°C ± 2°C and a humidity of RH 75% ± 5%, and samples were taken at the end of 1 month, 3 months and 6 months, and the related substances were detected.

[0057] (2) Related substance determination condition: according to high performance liquid chromatography, octadecylsilane bonded silica gel is used as the filler, and di-potassium hydrogen phosphate aqueous solution-acetonitrile is used as the mobile phase for determination. A suitable amount of sample is accurately measured and diluted with the mobile phase to 5 mg / mL as the test solution; the test solution is accurately measured into a 25 mL volumetric flask, diluted with the mobile phase to constant volume as the self-control. The injection amount is 20 uL, the flow rate is 1.0 mL / min, and the total amount of related impurities should not exceed 3.0%.

[0058] (3) Dissolution determination: the sample is weighed, and the dissolution determination method (Chinese Pharmacopoeia 2020 edition fourth part general rule 0931 second method) is used with 900 ml of phosphate buffer (pH 6.8) as the dissolution medium, the rotation speed is 50 revolutions per minute, the operation is carried out according to the law, after 30 minutes, 10 ml of solution is taken and filtered, 5 ml of filtrate is accurately measured, placed in a 25 ml volumetric flask as the sample solution, and the control solution is prepared. Dissolution detection method: the chromatographic conditions are C18 chromatographic column, the mobile phase is 0.1% phosphoric acid: acetonitrile = 68:32 (v / v), the injection amount is 20 uL, and the flow rate is 1.0 mL / min.

[0059] The determination results are shown in Table 6.

[0060] Table 6

[0061] As can be seen from Table 6, the stability of the orally disintegrating tablets prepared from coated granules in Examples 1-3 and Comparative Example 3 is good, and the impurity growth is slow, while the impurity of the orally disintegrating tablets prepared without coating in Comparative Example 4 increases obviously, which shows that coating the whole granule can significantly inhibit the generation of impurities. Compared with Comparative Example 3 which uses insoluble coating material to coat the granules, the dissolution of the orally disintegrating tablets of Examples 1-3 is significantly improved, which helps to improve the bioavailability of the drug.

[0062] Test Example 3 The orally disintegrating tablets obtained from Example 4 and Comparative Examples 5-6 were respectively placed in a stability test box with a temperature of 40℃±2℃ and a humidity of RH75%±5% for 0 days, 5 days and 10 days, and the disintegration time and hardness change were investigated, and the results are shown in Table 7.

[0063] Table 7

[0064] As shown in Table 7, the oral disintegration tablet in the prescription of Comparative Example 6 does not use silicon dioxide, and the hardness of the tablet decreases significantly and the disintegration is obviously slowed down after 0 days and 10 days of accelerated test; the hydrophilic silicon dioxide used in Comparative Example 5 has a certain barrier effect on water, but the effect is not obvious, the disintegration speed is slowed down, and the hardness is also obviously decreased; while in Example 4, the hydrophobic silicon dioxide has obvious effect on blocking external water, and the obtained oral disintegration tablet has good stability, and the disintegration speed of the oral disintegration tablet is basically unchanged and the average hardness is slightly decreased with the extension of the accelerated test time.

[0065] Test Example 4 Twenty persons were invited and randomly divided into 4 groups, 5 persons in each group, and the oral disintegration time of the oral disintegration tablets obtained in Examples 5-6 and Comparative Examples 7-8 was determined: no water was taken, the test person placed the experimental sample on the tongue, closed the mouth to make the oral disintegration tablet against the upper palate in the oral cavity, and after the oral disintegration tablet completely disintegrated, the disintegration time was recorded. The test results are shown in Table 8.

[0066] Table 8

[0067] As shown in Table 8, the oral disintegration tablets prepared with the same prescription and different tablet thicknesses have decreased hardness and disintegration time (Comparative Example 7) with the increase of tablet thickness, but the tablet in Comparative Example 8 is thick, and when the disintegration time of the oral disintegration tablet is detected by the disintegration tester, it floats on the liquid surface, and the wetting time is obviously prolonged, so the in vitro disintegration time is the longest; while the in oral disintegration results show that the disintegration time is faster with the decrease of tablet thickness, which indicates that the thickness of the oral disintegration tablet has great influence on the disintegration time.

[0068] The above is only the preferred specific embodiment of the present application, but the protection scope of the present application is not limited thereto, any person skilled in the art can make equivalent replacement or change according to the technical solution and the inventive concept of the present application within the technical range disclosed by the present application, which should be covered in the protection scope of the present application.

Claims

1. An opicapone orally disintegrating tablet, characterized in that, The oral disintegration tablet of the opicapone comprises, by weight ratio, 5.0%-30.0% of opicapone, 55.0%-75.0% of a water-soluble filler, 0.5%-3.0% of hydrophobic silicon dioxide, 4.0%-11.0% of a disintegrant, and 0.9%-2.0% of a coating material; wherein the water-soluble filler is a high-density water-soluble filler with a density ≥ 0.5 g / ml.

2. The opicapone orally disintegrating tablet according to claim 1, wherein The thickness of the oral disintegration tablet of the opicapone is ≤ 3.0 mm, and the average hardness is 5.0-8.0 kN.

3. The opicapone orally disintegrating tablet according to claim 1, wherein The high-density water-soluble filler is selected from at least one of mannitol, lactose, sorbitol, and maltitol; The disintegrant is selected from at least one of crospovidone, sodium carboxymethyl starch, low-substituted hydroxypropyl methyl cellulose, and cross-linked sodium carboxymethyl cellulose.

4. The opicapone orally disintegrating tablet according to claim 3, wherein The coating material is a water-soluble coating material selected from at least one of hydroxypropyl methyl cellulose, hydroxypropyl cellulose, and polyvinyl alcohol.

5. The oral disintegrating tablet according to any one of claims 1 to 4, wherein The oral disintegration tablet of the opicapone further comprises, by weight ratio, 2.5%-3.0% of a binder, 2.5%-5.0% of a flavoring agent, and 0.8%-1.2% of a lubricant.

6. The oral disintegrating tablet according to claim 5, wherein The binder is selected from at least one of starch, dextrin, povidone, copovidone, hydroxypropyl cellulose, and hydroxypropyl methyl cellulose; The flavoring agent is selected from at least one of xylitol, aspartame, sucralose, neotame, banana flavor, pineapple flavor, orange flavor, orange flavor, mint flavor, and strawberry flavor; The lubricant is selected from at least one of magnesium stearate, calcium stearate, glycerol monostearate, sodium stearyl fumarate, and talc.

7. A process for the preparation of an oral disintegrating tablet of opicapone, characterized by the steps of The method comprises: granulating and drying the raw material opicapone, the water-soluble filler, the binder, and the disintegrant to obtain opicapone granules; dissolving the coating material in water and then performing bottom-spray coating in a fluidized bed to obtain coated granules; mixing the coated granules, the hydrophobic silicon dioxide, the flavoring agent, the lubricant, and the disintegrant uniformly and then pressing them into tablets to obtain the oral disintegration tablet of the opicapone.

8. The preparation method of the opicapone orally disintegrating tablet according to claim 7, characterized by, The granulation process is wet granulation, extrusion-spheronization granulation, or fluidized bed one-step granulation.

9. The preparation method of the opicapone orally disintegrating tablet according to claim 7, characterized by, The particle size of the opicapone granules is 200-800 μm, and the bulk density is ≥ 0.5 g / ml.

10. The preparation method of the opicapone orally disintegrating tablet according to claim 7, characterized by, The coating weight gain of the granules during coating is 0.3%-3.0%.

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