Opiapone pharmaceutical composition and preparation method thereof

Abstract

The invention discloses an omicapone pharmaceutical composition and a preparation method thereof, and belongs to the technical field of pharmaceutical preparations. Comprising an opiapone compound which is a particle with specific size characteristics that the D10 diameter is not less than 4 [mu] m, the D50 diameter is 10-45 [mu] m and the D95 diameter is less than or equal to 80 [mu] m, and a pharmaceutically acceptable carrier of the particle is prepared into a tablet or a capsule. The opiapone preparation provided by the invention has the advantages of high dissolution rate, good stability, high safety, simple preparation process and the like.

Description

Technical Field

[0001] The invention discloses an opicapone pharmaceutical composition and a preparation method thereof, and belongs to the technical field of pharmaceutical preparations. Background Art

[0002] Parkinson's disease is a progressive neurological disease caused by the death of dopamine neurons. The disease is common worldwide, most commonly in people over 50 years old. Opicapone is a peripheral, selective and reversible COMT inhibitor that inhibits peripheral levodopa metabolism and increases the amount of levodopa delivered, thus being used as an add-on therapy to levodopa to enhance the efficacy of levodopa. Opicapone is a catechol-O-methyltransferase (COMT) inhibitor that can be used to treat Parkinson's patients in the "off" phase as an adjunct to levodopa / carbidopa. Opicapone is the first and only COMT inhibitor that can reduce the "off" phase without causing movement disorders. As a new third-generation COMT inhibitor, opicapone can produce potent and persistent inhibitory activity, reduce the metabolism of levodopa, allow more levodopa to reach the brain, better exert the drug's efficacy, and help patients achieve motor symptom control. Opicapone is a low-solubility, high-permeability drug, that is, the dissolution of a Biopharmaceutics Classification System (BCS) Class II drug is the rate-limiting step for oral absorption. The opicapone pharmaceutical composition prepared by the present invention has the advantages of high solubility, good stability, high safety, simple preparation process, etc. Summary of the invention

[0003] In order to develop a more stable and effective opicapone pharmaceutical preparation, the inventors conducted a long and in-depth study on the physicochemical properties of opicapone, and screened and prepared a more stable capsule preparation with better bioequivalence and higher safety based on a large number of experiments.

[0004] The present invention adopts the following technical solutions: Opicapone has particles of specific size specifications, among which the D10 diameter is not less than 4μm, the D50 diameter is 10-45μm, and the D95 diameter is less than 80μm. The structural formula is shown in the appendix of the manual. Figure 1 .

[0005] The compound microparticles of the present invention are prepared by micronization using ball milling or spiral jet milling.

[0006] The compound particles of the present invention have a particle size specification of a D10 diameter of not less than 5 μm.

[0007] The compound particles of the present invention have a particle size specification of D50 diameter of 15-30 μm.

[0008] The pharmaceutical composition in a unit dosage form for oral administration of the present invention comprises an opicapone compound, which is a particle having specific size characteristics of a D10 diameter of not less than 4 μm, a D50 diameter of 10-45 μm and a D90 diameter of less than or equal to 80 μm, and a pharmaceutically acceptable carrier thereof.

[0009] The pharmaceutical composition of the present invention, wherein the unit dosage form is a tablet or a capsule.

[0010] A method for treating a patient suffering from Parkinson's disease comprises administering to the patient an effective amount of the pharmaceutical composition described above.

[0011] The method of the present invention, wherein the unit dosage form is a tablet or a capsule.

[0012] The compound of the present invention, wherein the compound particles have a particle size specification of D10 diameter not less than 20 μm.

[0013] The compound of the present invention, wherein the compound particles have a particle size specification of D50 diameter not less than 20-25 μm. Implementation

[0014] The Opicapone capsules of the present invention are further described by the following examples, but the present invention is not limited to the following examples. Example

[0015] Amount of raw materials and auxiliary drugs (%) Opicapone 25% Lactose 64% Sodium starch glycolate 4% Pregelatinized starch 6% Magnesium Stearate 1% Preparation method: Opicapone is micronized to ensure that the particle size distribution D50 is 10-45 μm; take the prescribed amount of opicapone and the prescribed amount of lactose, pregelatinized starch and sodium starch glycolate; mix them evenly, and then mix them evenly with magnesium stearate, test the content of the semi-finished product, fill it into non-gelatin capsules or compress it into tablets. Example

[0016] Amount of raw materials and auxiliary drugs (%) Opicapone 25% Mannitol 62% Sodium starch glycolate 2% Corn starch 10% Magnesium Stearate 1% Preparation method: Same as above. Example

[0017] Amount of raw materials and auxiliary drugs (%) Opicapone 25% Lactose 62% PVPP 2% Corn starch 10% Magnesium Stearate 1% Preparation method: Same as above. Example

[0018] Amount of raw materials and auxiliary drugs (%) Opicapone 25% Lactose 62% Croscarmellose Sodium 2% Pregelatinized starch 4% Magnesium Stearate 1% Preparation method: Same as above. Example

[0019] Amount of raw materials and auxiliary drugs (%) Opicapone 25% Starch oligosaccharide 62% Croscarmellose Sodium 2% Pregelatinized starch 4% Magnesium Stearate 1% Preparation method: Same as above.

[0020] Comparative Example 1 Amount of raw materials and auxiliary drugs (%) Opicapone 25% Lactose 64% Sodium starch glycolate 4% Pregelatinized starch 6% Magnesium Stearate 1% Preparation method: Opicapone is micronized to ensure that the particle size distribution D50 is greater than 45 μm; the prescribed amount of opicapone is mixed with the prescribed amount of lactose, pregelatinized starch and sodium starch glycolate; the mixture is evenly mixed, and then the mixture is evenly mixed with magnesium stearate, the content of the semi-finished product is tested, and the semi-finished product is filled into non-gelatin capsules or pressed into tablets. Example

[0021] Amount of raw materials and auxiliary drugs (%) Opicapone 25% Mannitol 62% Sodium starch glycolate 2% Corn starch 10% Magnesium Stearate 1% Preparation method: micronize opicapone to ensure that the particle size distribution D50 is less than 10 μm; take the prescribed amount of opicapone and the prescribed amount of mannitol, corn starch and sodium starch glycolate; mix them evenly, and then mix them evenly with magnesium stearate, test the content of the semi-finished product, fill it into non-gelatin capsules or compress it into tablets.

[0022] The dissolution results of the examples and comparative examples are compared in the appendix of the specification. Figure 2 By the attached Figure 2 It can be seen that the dissolution of the pharmaceutical composition prepared according to the embodiment of the present invention is significantly better than that of the comparative example; from the above results, it can be seen that the dissolution and stability of the pharmaceutical composition prepared according to the present invention are better than those of the comparative example, and the preparation process is simple, which is suitable for large-scale industrial production.

[0023] The above embodiments are only preferred embodiments for fully illustrating the present invention, and the protection scope of the present invention is not limited thereto. Any equivalent substitution or change made by a person skilled in the art based on the present invention is within the protection scope of the present invention.

[0024] Description of the drawings Attached Figure 1 The structural formula of opicapone Attached Figure 2 This is a comparative study on the dissolution of opicapone in hydrochloric acid at pH 1.2.

Claims

1. An opicapone pharmaceutical composition and a preparation method thereof, characterized in that: Opicapone in the pharmaceutical composition is a particle with specific size specifications, wherein the D10 diameter is not less than 4 μm, the D50 diameter is 10-45 μm, and the D95 diameter is less than 80 μm. The structural formula is as follows 。 2. The compound according to claim 1, wherein the microparticle form is prepared by ball milling or by micronization in a spiral jet mill.

3. The compound according to claim 1, wherein the compound particles have a particle size specification of D10 diameter not less than 5 μm.

4. The compound according to claim 1, wherein the compound particles have a particle size specification of D50 diameter of 15-30 μm.

5. A pharmaceutical composition in a unit dosage form for oral administration, comprising a compound of opicapone in the form of microparticles of a specific size having a D10 diameter of not less than 4 μm, a D50 diameter of 10-45 μm and a D90 diameter of less than or equal to 80 μm and a pharmaceutically acceptable carrier thereof.

6. The pharmaceutical composition according to claim 6, wherein the unit dosage form is a tablet or a capsule.

7. A method for treating patients suffering from Parkinson's disease, comprising administering an effective amount of the pharmaceutical composition according to claim 6 to the patient.

8. The method of claim 8, wherein the unit dosage form is a tablet or a capsule.

9. The compound according to claim 1, wherein the compound particles have a particle size specification of D10 diameter not less than 20 μm.

10. The compound according to claim 1, wherein the compound microparticles have a particle size specification of D50 diameter of 20-25 μm.

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