Pregabalin preparation containing compound auxiliary materials and preparation method of pregabalin preparation

Abstract

The invention provides a pregabalin preparation containing compound auxiliary materials and a preparation method of the pregabalin preparation. The pregabalin preparation is prepared from the following raw materials: pregabalin, a filling agent, a disintegrating agent, a flow aid, an anti-sticking agent, an emulsifying agent, a flavoring agent and a lubricating agent, the preparation method comprises the following steps: adding an emulsifier, an anti-sticking agent and a part of filler into purified water, uniformly mixing, then adding the balance of filler, a disintegrating agent and a flow aid, uniformly mixing, and carrying out spray drying to obtain a compound auxiliary material; and mixing pregabalin, the compound auxiliary material, a flavoring agent and a lubricant, and tabletting. According to the pregabalin tablet and the preparation method thereof, part of the auxiliary materials are prepared into the compound auxiliary materials through a spray drying method, then the compound auxiliary materials are mixed with the pregabalin raw material medicine and other auxiliary materials to be tableted, so that the tableting process is better controlled, the problems of easiness in sticking, low tablet hardness, poor friability, low disintegration speed and the like in the tableting process are solved, and the prepared pregabalin tablet is high in hardness, good in stability and good in stability. The pregabalin preparation is good in friability and fast in disintegration.

Description

Technical Field

[0001] The present invention relates to the technical field of pharmaceutical preparations, and in particular to a pregabalin preparation comprising compound excipients and a preparation method thereof. Background Art

[0002] Pregabalin is a γ-aminobutyric acid derivative that has been approved for multiple indications worldwide, including diabetic peripheral neuropathy, postherpetic neuralgia, fibromyalgia syndrome, neuralgia caused by spinal cord injury, and as an adjuvant therapy for partial epileptic seizures in adult patients. The orodisintegrating tablet is a new type of drug preparation that can automatically disintegrate into countless particles and taste sweet within 60 seconds after being placed on the tongue. Because it disintegrates quickly, is absorbed quickly, and does not require drinking water after taking the medicine, it is very suitable for some special patients (mental illness, Alzheimer's disease, epilepsy patients, etc.) and the elderly and children.

[0003] Since orally disintegrating tablets need to achieve a relatively fast disintegration rate (disintegration time is less than 60s), the prescription often contains more disintegrants. Due to the influence of the properties of the disintegrants themselves, orally disintegrating tablets often have undesirable phenomena such as sticking and poor friability during the tableting process, which affects the product quality. Therefore, it is necessary to prepare a pregabalin orally disintegrating tablet with high hardness, good friability and fast disintegration to meet the product quality requirements.

[0004] At present, the preparation methods of pregabalin orodisintegrating tablets on the market include freeze-drying process, direct powder compression process, and wet granulation process. Although the orodisintegrating tablets prepared by freeze-drying are loose and porous and disintegrate quickly, the product has poor brittleness, is easy to break, and is not convenient for packaging and transportation; the direct powder compression process does not involve granulation, so the disintegrant in the prescription is directly exposed, and undesirable phenomena such as sticking and punching are prone to occur during the tableting process; the wet granulation process causes the disintegrant to contact water during the wet granulation process and then be dried again, resulting in a decrease in its disintegration performance, which in turn slows down the product disintegration rate. Therefore, the various performances of pregabalin orodisintegrating tablets need to be further improved. Summary of the invention

[0005] The first object of the present invention is to provide a pregabalin preparation comprising a compound excipient to solve the problems of easy sticking, low hardness, poor friability, slow disintegration rate, etc. of the existing pregabalin preparation during tableting.

[0006] The present invention provides a method for preparing a pregabalin preparation containing compound excipients, wherein the raw materials include pregabalin, a filler, a disintegrant, a glidant, an anti-adherent, an emulsifier, a flavoring agent and a lubricant; The preparation method comprises: adding an emulsifier, an anti-adherent and a part of a filler to purified water, mixing evenly, then adding the remaining filler, a disintegrant and a glidant, mixing evenly and spray drying to obtain a composite auxiliary material; Pregabalin, the compound excipients, flavoring agents and lubricants are mixed and then tableted.

[0007] The present invention prepares a composite excipient by spray drying part of the excipients, and then compresses the composite excipients after mixing the composite excipients with the pregabalin raw material and other excipients, so as to better control the tableting process, thereby solving the problems of easy sticking, low tablet hardness, poor friability, slow disintegration speed, etc. in the tableting process, and obtains a pregabalin preparation with high hardness, good friability and fast disintegration.

[0008] Preferably, the raw materials of the pregabalin preparation include the following components in parts by weight: 140-160 parts of pregabalin, 220-260 parts of filler, 10-20 parts of disintegrant (preferably 12-18 parts), 12-18 parts of glidant, 8-12 parts of anti-adherent, 10-20 parts of emulsifier (preferably 12-18 parts), 16-28 parts of flavoring agent, and 12-24 parts of lubricant.

[0009] The preparation method provided by the present invention uses purified water to dissolve the filler, emulsifier, anti-adherent, disintegrant and glidant for subsequent freeze drying. The amount of water used has a great influence on the effect of spray drying. The present invention preferably uses a weight ratio of purified water to the compound excipient (i.e., equivalent to the total weight of the filler, emulsifier, anti-adherent, disintegrant and glidant) of 4:1-2:1, preferably 2.5-3:1, and more preferably 2.7:1. Within the above dosage range, it is beneficial to prepare a compound excipient with a particle size of 80-150 μm, and the bulk density of the compound excipient is 0.45-0.6 g / cm 3 .

[0010] In order to better promote the uniform dispersion of excipients and thus ensure the quality of freeze-drying, the filler is divided into two parts and mixed with other excipients. Preferably, the partial filler is 1.5 to 2.5 times the weight of the remaining filler, and more preferably 2 times. Through the reasonable distribution of the filler, a compound excipient with more uniform particle size, narrower particle size distribution and better fluidity (angle of repose less than 35°) can be obtained.

[0011] The preparation method provided by the present invention comprises the following spray drying conditions: air inlet temperature of 110-150°C, fan frequency of 35-50Hz, spray gun atomization pressure of 0.2-0.3MPa; and preferably the spray gun caliber is 1.0mm.

[0012] Under the above-mentioned spray drying conditions, it is further beneficial to control the uniformity of particle size, particle size distribution and fluidity, and it can also promote the smooth progress of the subsequent tableting process, improve tablet hardness and accelerate disintegration speed.

[0013] Preferably, after spray drying, the obtained excipient complex is passed through a 24-mesh sieve to obtain a more ideal particle size, and the compound excipient is obtained by granulation; or the particle size of the compound excipient is controlled to be between No. 3 sieve and No. 5 sieve, accounting for ≥80%.

[0014] The preparation method provided by the present invention comprises the following steps: after the compound excipients are prepared, pregabalin, the compound excipients and the flavoring agent are firstly mixed, and then a lubricant is added, and the mixture is mixed and then tabletted; preferably, an 11 mm round shallow concave punch is used for tabletting; the main pressure is 8-12 KN; under the above tabletting conditions, the tabletting process is smooth, the tablet hardness is high, and undesirable phenomena such as sticking to the punch and tablet cracking will not occur.

[0015] The present invention adopts a powder direct tableting process, and since the disintegrant does not contact water, good disintegration performance is maintained, thereby ensuring that the prepared pregabalin orally disintegrating tablet has a faster disintegration speed.

[0016] The pregabalin preparation of the present invention can be made of various commonly used raw materials disclosed in the prior art (preferably: The filler of the present invention is selected from one or more of microcrystalline cellulose, mannitol, starch, lactose, calcium hydrogen phosphate, and sorbitol; preferably microcrystalline cellulose and mannitol (more preferably, the ratio of microcrystalline cellulose to mannitol is 1:1.5-2.5, preferably 1:1), so as to obtain a bulk density of 0.45-0.6 g / cm 3 The compound auxiliary material, the amount of the filler is preferably 220-260 parts.

[0017] In some embodiments provided by the present invention, the filler includes microcrystalline cellulose and mannitol in a ratio of 1:1.5 to 2.5. When preparing compound excipients, mannitol is mixed with an emulsifier and an anti-adherent; and microcrystalline cellulose is mixed with a disintegrant and a glidant.

[0018] The disintegrant of the present invention is selected from one or more of cross-linked polyvinylpyrrolidone, cross-linked sodium carboxymethyl cellulose, sodium carboxymethyl starch, hydroxypropyl cellulose, and dry starch; preferably cross-linked polyvinylpyrrolidone, which has a faster disintegration rate, and the appropriate dosage is 10 to 20 parts, especially 12 to 18 parts.

[0019] The glidant of the present invention is selected from one or more of magnesium aluminum metasilicate and silicon dioxide, preferably magnesium aluminum metasilicate, which has excellent material fluidity and stable tablet weight during tableting. The appropriate dosage is 12 to 18 parts.

[0020] The anti-adhesive agent of the present invention is selected from one or more of hydrogenated castor oil, talc and silicon dioxide, preferably hydrogenated castor oil; the appropriate amount thereof is 5 mg to 15 mg per tablet, or in parts by weight, the amount thereof in the raw material is preferably 8 to 12 parts.

[0021] The lubricant of the present invention is selected from one or more of talc, magnesium stearate, calcium stearate, glyceryl behenate, and sodium stearyl fumarate, preferably a mixture of magnesium stearate, talc and sodium stearyl fumarate, and the mixing ratio of the three is preferably 1:1:1, which is more conducive to promoting an ideal tableting process. The amount of the lubricant is preferably 12 to 24 parts.

[0022] The emulsifier of the present invention is selected from one or more of polyglycerol fatty acid esters, sucrose fatty acid esters, sodium lauryl sulfate, soybean lecithin, and egg yolk lecithin, preferably polyglycerol fatty acid esters. The amount of the emulsifier in the raw material is preferably 10 mg to 10 mg per tablet, or in parts by weight, the amount in the raw material is preferably 10 to 20 parts, especially 12 to 18 parts.

[0023] The flavoring agent described in the present invention can be selected from known common flavoring agents, such as saccharin sodium, sucralose, orange flavor, etc., preferably a mixture of the three. The specific amount can be selected by those skilled in the art at their discretion, and the present invention does not make any special limitation on this.

[0024] As a preferred embodiment of the present invention, the pregabalin preparation containing compound excipients comprises the following components by weight: 140-160 parts of pregabalin, 70-90 parts of microcrystalline cellulose (preferably 75-85 parts), 150-170 parts of mannitol, 10-20 parts of cross-linked polyvinylpyrrolidone (preferably 12-18 parts), 12-18 parts of magnesium aluminum metasilicate, 8-12 parts of hydrogenated castor oil, 10-20 parts of polyglycerol fatty acid ester (preferably 12-18 parts), 4-8 parts of saccharin sodium, 4-8 parts of sucralose, 8-12 parts of orange flavor, 4-8 parts of magnesium stearate, 4-8 parts of talc, and 4-8 parts of sodium stearyl fumarate.

[0025] More preferably, the prescription of the pregabalin preparation containing compound excipients is as follows: 150 parts of pregabalin, 80 parts of microcrystalline cellulose, 160 parts of mannitol, 15 parts of crospovidone, 15 parts of magnesium aluminum metasilicate, 10 parts of hydrogenated castor oil, 15 parts of polyglycerol fatty acid ester, 5 parts of saccharin sodium, 5 parts of sucralose, 10 parts of orange flavor, 5 parts of magnesium stearate, 5 parts of talc, and 5 parts of sodium stearyl fumarate.

[0026] The second object of the present invention is to provide a pregabalin preparation prepared by the above method, wherein the preparation is preferably an orally disintegrating tablet.

[0027] Based on the fact that orally disintegrating tablets generally contain more disintegrants, which are easy to stick to the punches, the present invention first prepares the disintegrants and some specific excipients into compound excipients, so that the disintegrants are wrapped by other excipients, and the contact between the disintegrants and the tablet press during the tableting process is reduced, thereby ensuring that the tableting process is smooth, does not stick to the punches, and the tablets have high hardness and good friability. The present invention improves the preparation process, and the obtained preparation has higher hardness, smaller friability, and faster disintegration speed than the existing marketed products. In addition, the tableting process is smooth in preparation, and no undesirable phenomena such as sticking to the punches occur. DETAILED DESCRIPTION

[0028] In order to make the purpose, technical solution and advantages of the present invention clearer, the technical solution of the present invention is described clearly and completely below. Obviously, the described embodiments are part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0029] Example 1: Pregabalin orally disintegrating tablets

[0030] This embodiment provides a pregabalin orally disintegrating tablet, the prescription composition of which is as follows:

[0031] This embodiment also provides a method for preparing the above-mentioned pregabalin orally disintegrating tablets, which specifically comprises the following steps: (1) Preparation of compound excipients

[0032] a. Liquid preparation: Take 800 ml of purified water, add the prescribed amount of mannitol, polyglycerol fatty acid ester, and hydrogenated castor oil, and stir until completely dissolved. Then add the prescribed amount of microcrystalline cellulose, cross-linked polyvinylpyrrolidone, and magnesium aluminum metasilicate, and stir for 10 minutes to disperse evenly. b. Spray drying: spray drying the prepared liquid with a spray dryer, air inlet temperature 110~130℃, spray gun caliber: 1.0mm, fan frequency: 35~45Hz, spray gun atomization pressure: 0.2~0.3MPa; c. Granulation: Pass the spray-dried composite through a 24-mesh sieve to obtain compound excipients; (2) Sample preparation

[0033] a. Premixing: Take the prescribed amount of pregabalin API, compound excipients, saccharin sodium, sucralose, and orange flavor, place in a three-dimensional mixer, and mix for 20 minutes; b. Total mixing: Add the prescribed amount of magnesium stearate, talc, and sodium stearyl fumarate and continue mixing for 10 minutes; c. Tablet pressing: Use 11mm round shallow concave punch for tablet pressing, control the tablet weight to 480mg, and set the main pressure of the tablet press at 8~12KN.

[0034] Example 2

[0035] Compared with Example 1, the only difference is that the specific conditions for preparing the compound excipients in step (1) are different, specifically: a. Liquid preparation: Take 900 ml of purified water, add the prescribed amount of mannitol, polyglycerol fatty acid ester, and hydrogenated castor oil, stir until completely dissolved, then add the prescribed amount of microcrystalline cellulose, cross-linked polyvinylpyrrolidone, and aluminum magnesium metasilicate, stir for 10 minutes and disperse evenly; b. Spray drying: spray drying the prepared liquid with a spray dryer, air inlet temperature 120~130℃, spray gun caliber: 1.0mm, fan frequency: 40~45Hz, spray gun atomization pressure: 0.25~0.3MPa; c. Granulation: Pass the spray-dried composite through a 24-mesh sieve to obtain compound excipients.

[0036] Example 3

[0037] Compared with Example 1, the only difference is that the specific conditions for preparing the compound excipients in step (1) are different, specifically: a. Liquid preparation: Take 1000 ml of purified water, add the prescribed amount of mannitol, polyglycerol fatty acid ester, and hydrogenated castor oil, and stir until completely dissolved. Then add the prescribed amount of microcrystalline cellulose, cross-linked polyvinylpyrrolidone, and magnesium aluminum metasilicate, and stir for 10 minutes to disperse evenly. b. Spray drying: spray drying the prepared liquid with a spray dryer, air inlet temperature 110~125℃, spray gun caliber: 1.0mm, fan frequency: 35~40Hz, spray gun atomization pressure: 0.2~0.3MPa; c. Granulation: Pass the spray-dried composite through a 24-mesh sieve to obtain compound excipients.

[0038] Example 4

[0039] Compared with Example 1, the only difference is that the specific conditions for preparing the compound excipients in step (1) are different, specifically: a. Liquid preparation: Take 950 ml of purified water, add the prescribed amount of mannitol, polyglycerol fatty acid esters, and hydrogenated castor oil and stir until completely dissolved, then add the prescribed amount of microcrystalline cellulose, cross-linked polyvinylpyrrolidone, and magnesium aluminum metasilicate and stir for 10 minutes to disperse evenly; b. Spray drying: spray drying the prepared liquid with a spray dryer, air inlet temperature 140~150℃, spray gun caliber: 1.0mm, fan frequency: 40~50Hz, spray gun atomization pressure: 0.2~0.3MPa; c. Granulation: Pass the spray-dried composite through a 24-mesh sieve to obtain compound excipients.

[0040] Example 5

[0041] Compared with Example 1, the only difference is that the prescription is different, specifically:

[0042] Example 6

[0043] Compared with Example 1, the only difference is that the prescription is different, specifically:

[0044] Comparative Example 1: Pregabalin orally disintegrating tablets (using powder direct tableting process)

[0045] This comparative example provides a pregabalin orally disintegrating tablet, the prescription composition of which is as follows:

[0046] This comparative example also provides a method for preparing the above-mentioned pregabalin orally disintegrating tablets, which specifically comprises the following steps: a. Premixing: Take the prescribed amount of pregabalin API, microcrystalline cellulose, mannitol, cross-linked polyvinylpyrrolidone, magnesium aluminum metasilicate, hydrogenated castor oil, polyglycerol fatty acid ester, saccharin sodium, sucralose, and orange flavor, place in a three-dimensional mixer, and mix for 20 minutes; b. Total mixing: Add the prescribed amount of magnesium stearate, talc, and sodium stearyl fumarate and continue mixing for 10 minutes; c. Tablet pressing: Use 11mm round shallow concave punch for tablet pressing, control the tablet weight to 480mg, and the main pressure of the tablet press is 8~12KN.

[0047] Comparative Example 2: Pregabalin orally disintegrating tablets (using freeze-drying process)

[0048] This comparative example provides a pregabalin orally disintegrating tablet, the prescription composition of which is as follows:

[0049] This comparative example also provides a method for preparing the above-mentioned pregabalin orally disintegrating tablets, which specifically comprises the following steps: a. Liquid preparation: Take 800 ml of purified water, add the prescribed amount of pregabalin API, mannitol, sodium saccharin, hydrogenated castor oil, polyglycerol fatty acid ester, sucralose in sequence, stir until completely dissolved, then add the prescribed amount of microcrystalline cellulose, cross-linked polyvinylpyrrolidone, magnesium aluminum metasilicate, orange flavor, magnesium stearate, talc, sodium stearyl fumarate, stir for 15 minutes to disperse evenly, and obtain a suspension solution; b. Packaging: Pack the suspension into freeze-dried tablet molds; c. Freeze-drying: Place the subpackaged suspension into a freeze dryer for freeze-drying, with a pre-freezing temperature of -40°C, a sublimation drying temperature of -10°C, maintained for 20 hours, and a desorption drying temperature of 30°C, maintained for 8 hours, and the moisture content of the product controlled to be less than 2.0%.

[0050] Comparative Example 3: Pregabalin orally disintegrating tablets (using wet granulation process)

[0051] This comparative example provides a pregabalin orally disintegrating tablet, the prescription composition of which is as follows:

[0052] This comparative example also provides a method for preparing the above-mentioned pregabalin orally disintegrating tablets, which specifically comprises the following steps: a. Premixing: Take the prescribed amount of pregabalin API, microcrystalline cellulose, mannitol, crospovidone, magnesium aluminum metasilicate, hydrogenated castor oil, polyglycerol fatty acid ester, saccharin sodium, sucralose, and orange flavor, place in a wet granulator, start stirring at 200 rpm, shear at 1500 rpm, and mix for 10 min; b. Granulation: Add 96g (20% of the prescription amount) of purified water for wet granulation, stir at 200rpm, shear at 1500rpm, wet mix for 3min, and pass the soft material through a 24h sieve for wet granulation; c. Drying: The wet granules are placed in an oven at 60°C for drying, and the moisture content of the dry granules is controlled to be less than 2.0%; d. Granulation: The dry granules are sieved through a 24-mesh sieve for granulation; e. Total mixing: Add the whole dry granules and the prescribed amount of magnesium stearate, talc and sodium stearyl fumarate into a three-dimensional mixer and mix for 10 minutes; c. Tablet pressing: Use 11mm round shallow concave punch for tablet pressing, control the tablet weight to 480mg, and the main pressure of the tablet press is 5~8KN.

[0053] Comparative Example 4

[0054] This comparative example provides a method for preparing pregabalin orally disintegrating tablets. Compared with Example 1, the only difference is the liquid preparation stage in step a, which is as follows: a. Liquid preparation: Take 1200 ml of purified water, add the prescribed amount of mannitol, polyglycerol fatty acid esters, and hydrogenated castor oil, stir until completely dissolved, then add the prescribed amount of cross-linked polyvinylpyrrolidone, microcrystalline cellulose, and magnesium aluminum metasilicate, stir for 10 minutes and disperse evenly.

[0055] Test Example 1

[0056] This test example tests the specific quality indicators of the pregabalin orally disintegrating tablets prepared in the examples and comparative examples of the present invention.

[0057] 1. Stability test

[0058] In the technical solution of the present invention, part of the excipients are first prepared into compound excipients, and then mixed with the raw material and other excipients for tableting. The tableting process is smooth, the tablet weight is stable, and there are no undesirable phenomena such as sticking and cracking. The prepared tablets have high hardness, low brittleness, and fast disintegration speed.

[0059] 2. Tableting effect detection

[0060] The tableting process monitoring and comparison were performed on Examples 1 to 6 of the present invention and Comparative Examples 1 to 4. The comparison results are shown in Table 1.

[0061] Table 1

[0062] The test results show that the surfaces of the tablets of Examples 1 to 6 and Comparative Example 2 are smooth and complete, and no undesirable phenomena such as sticking or punching occur during tableting, and the product properties meet the requirements; while the surface of the tablets prepared in Comparative Example 1 is not bright, and sticking or punching occurs after tableting for 5 minutes, indicating that spray drying of the excipients to prepare compound excipients or the use of a wet granulation process can reduce the contact area between the disintegrant and the punch, thereby reducing the risk of sticking or punching during tableting. The product prepared in Comparative Example 4 also has the disadvantages of large fluctuations in tablet weight, which exceeds the limit range requirements.

[0063] 3. Hardness, friability and disintegration time testing

[0064] The hardness, friability and disintegration time of Examples 1 to 6 of the present invention, Comparative Examples 1 to 4 and pregabalin orally disintegrating tablets available on the market were tested. The test results are shown in Table 2.

[0065] Among them, the pregabalin orodisintegrating tablets on sale are produced by Japan Viatris Pharmaceutical Co., Ltd. and the trade name is "Lyrica".

[0066] Table 2

[0067] The test results show that: since comparative example 1 adopts the direct powder tableting process, the product hardness is only 34.6N, resulting in a friability of 2.83%, which exceeds the limit requirement (limit requirement: not more than 1.0%); since comparative example 2 adopts the freeze-drying process, the product hardness is only 12.3N, and the product breaks during the friability test, which does not meet the requirements; comparative example 3 adopts the wet granulation process, and the product hardness and friability meet the requirements, but since the disintegrant absorbs water and then dries during the preparation process, the disintegration performance decreases, affecting the product disintegration time, resulting in unqualified disintegration time (limit requirement: not more than 60s); comparative example 4 has a large amount of purified water added to the compound excipient solution (low solid content), resulting in a small particle size of the compound excipient prepared by spray drying and poor fluidity, which leads to unstable tablet weight during the tableting process, exceeding the limit range requirements. The friability and disintegration time of pregabalin orodisintegrating tablets on the market are close to the limit requirements. In Example 1, part of the excipients in the prescription are prepared into compound excipients by spray drying technology, which improves the compressibility of the material while retaining the disintegration performance of the disintegrant. The product has a greater hardness, a smaller brittleness, and a faster disintegration speed, which meets the requirements.

[0068] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit it. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the aforementioned embodiments, or make equivalent replacements for some of the technical features therein. However, these modifications or replacements do not deviate the essence of the corresponding technical solutions from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A method for preparing a pregabalin preparation containing compound excipients, wherein the raw materials include pregabalin, a filler, a disintegrant, a glidant, an anti-adherent, an emulsifier, a flavoring agent and a lubricant; characterized in that: The preparation method comprises: Adding an emulsifier, an anti-adherent and a portion of a filler to purified water and mixing evenly, then adding the remaining filler, a disintegrant and a glidant, mixing evenly and spray drying to obtain a compound excipient; Pregabalin, the compound excipients, flavoring agents and lubricants are mixed and then tableted.

2. The preparation method according to claim 1, characterized in that: The weight ratio of the purified water to the compound auxiliary material is 4:1-2:1, preferably 2.5-3:

1.

3. The preparation method according to claim 1 or 2, characterized in that: The weight of the partial filler is 1.5 to 2.5 times, preferably 2 times, the weight of the remaining filler.

4. The preparation method according to any one of claims 1 to 3, characterized in that The spray drying conditions are: air inlet temperature 110-150°C, fan frequency 35-50Hz, spray gun atomization pressure 0.2-0.3MPa; preferably, the spray gun caliber is 1.0mm.

5. The preparation method according to any one of claims 1 to 4, characterized in that The spray-dried composite is passed through a 24-mesh sieve and granulated to obtain the compound excipient; or the particle size of the compound excipient is controlled so that the proportion between the No. 3 sieve and the No. 5 sieve is ≥80%.

6. The preparation method according to any one of claims 1 to 5, characterized in that Pregabalin, the compound excipients and the flavoring agent are first mixed, and then a lubricant is added. After mixing, tableting is performed; preferably, a 11 mm round shallow concave punch is used for tableting; and the main pressure is 8-12 KN.

7. The preparation method according to any one of claims 1 to 6, characterized in that The filler is selected from one or more of microcrystalline cellulose, mannitol, starch, lactose, calcium hydrogen phosphate, and sorbitol; and / or the disintegrant is selected from one or more of cross-linked polyvinylpyrrolidone, cross-linked sodium carboxymethyl cellulose, sodium carboxymethyl starch, hydroxypropyl cellulose, and dry starch.

8. The preparation method according to any one of claims 1 to 7, characterized in that The glidant is selected from one or more of magnesium aluminum metasilicate and silicon dioxide; and / or the anti-adhesive is selected from one or more of hydrogenated castor oil, talc, and silicon dioxide; and / or the lubricant is selected from one or more of talc, magnesium stearate, calcium stearate, glyceryl behenate, and sodium stearyl fumarate; and / or the emulsifier is selected from one or more of polyglycerol fatty acid esters, sucrose fatty acid esters, sodium lauryl sulfate, soybean lecithin, and egg yolk lecithin.

9. The preparation method according to any one of claims 1 to 8, characterized in that The raw materials of the pregabalin preparation include the following components in parts by weight: 140-160 parts of pregabalin, 70-90 parts of microcrystalline cellulose, 150-170 parts of mannitol, 10-20 parts of cross-linked polyvinylpyrrolidone, 12-18 parts of magnesium aluminum metasilicate, 8-12 parts of hydrogenated castor oil, 10-20 parts of polyglycerol fatty acid ester, 4-8 parts of saccharin sodium, 4-8 parts of sucralose, 8-12 parts of orange flavor, 4-8 parts of magnesium stearate, 4-8 parts of talc, and 4-8 parts of sodium stearyl fumarate.

10. A pregabalin preparation comprising a compound excipient, characterized in that: Prepared by the preparation method according to any one of claims 1 to 9.

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