TW201311236A - Celecoxib solid dispersion and its preparation method - Google Patents

Abstract

The present invention relates to a celecoxib solid dispersion and its preparation method. The solid dispersion of the invention comprises of celecoxib and carrier materials selected from one or more of polyvinylpyrrolidone, copovidone, polyvinylpolypyrrolidone, and the weight ratio of scaffold material/celecoxib can be low to 0.2: 1. It is prepared in the way that carrier materials and celecoxib are dissolved or dispersed in organic solvents, and then the organic solvent is removed by vacuum distillation or spray drying. The solid dispersion which is subjected to crush can be easily made into all kinds of solid dosage forms. The problem that celecoxib crude drug is difficult to smash is well solved by the invention. Furthermore, the solid formulations of the invention can be made by using few materials, and have a good stability and high bioavailability.

Description

Celecoxib solid dispersion and preparation method thereof

The present invention relates to a solid dispersion of celecoxib, a process for preparing the solid dispersion, and a solid preparation comprising the solid dispersion.

Celecoxib is a selective COX-2 inhibitor developed and marketed by Pfizer to relieve symptoms and signs of osteoarthritis (OA) and rheumatoid arthritis (RA). The US FDA approved celecoxib capsules (50 mg, 100 mg, 200 mg, and 400 mg) in 1998, and subsequently approved indications for familial adenomatous polyposis (FAP), acute pain, and primary dysmenorrhea, ankylosing spondylitis ( AS), juvenile rheumatoid arthritis, the drug is now available in the United States, Japan and other countries.

The celecoxib bulk drug is almost insoluble in water and poorly absorbed orally. Patent ZL99802185.7 discloses that the preparation of the celecoxib granules D _{90 is} less than 200 um according to a conventional method, and the reduction of the particle size of the drug substance can achieve the purpose of improving bioavailability. However, the celecoxib bulk drug has a low bulk density, and the raw material pulverization process tends to stick to a block, so micronization is difficult. Patent application CN102000018A discloses a solid dispersion of celecoxib and a preparation method thereof, wherein a celecoxib bulk drug and a polyethylene glycol having a molecular weight of more than 4000 are prepared into a solid dispersion by a melt method, and then prepared into a preparation according to a conventional method. Overcome the deficiencies of celecoxib raw materials difficult to smash. However, the preparation temperature is high, the viscosity of the molten polyethylene glycol is large, the celecoxib raw material is slowly dissolved, is not easy to be uniformly dissolved, and the operation is difficult, and polyethylene glycol is selected as a solid dispersion material, which is required for preparation of the preparation. Add antioxidants to ensure stability. In addition, polyethylene glycol is used to prepare a solid dispersion. 1 g of polyethylene glycol can dissolve up to 1.25 g of celecoxib. It is feasible for low-dose pills, but for high-dose pills, the amount of auxiliary materials is too large, which ultimately leads to difficulty in taking. High dose pills are sometimes necessary in the treatment of certain diseases.

Therefore, there is still a need to develop a celecoxib composition and a preparation method thereof, which not only overcome the defects in the nature of the drug substance, but also reduce the type and amount of the excipient, and expect to achieve a higher organism with a simple prescription. Utilization.

Through research, we have unexpectedly discovered a new solid dispersion of celecoxib, which has higher bioavailability, simple prescription, less dosage of excipients, easy operation, stable quality and strong controllability compared with the prior art. Good reproducibility and other advantages. Specifically, we have found that a small amount of carrier material and celecoxib can be used to prepare an amorphous solid dispersion. After preparation of the corresponding preparation, the dissolution and bioavailability can be significantly improved, and the preparation is stable. Easy to operate and reproducible.

The present invention provides a solid dispersion comprising celecoxib and a carrier material selected from one or more of polyvinylpyrrolidone, copovidone and crospovidone, and the inventors have unexpectedly discovered As long as the weight ratio of the carrier material to the active ingredient celecoxib is 0.2:1 or more, the crystal state of the celecoxib can be changed to become an amorphous substance, thereby improving the absorption of the drug, and the drug is prepared after oral administration. It has high efficiency and high bioavailability, thereby reducing the amount of excipients and facilitating the preparation of high-dose formulations. And the solid dispersion itself is stable when it is prepared into a formulation No need to add antioxidants. The preparation method of the invention not only avoids the pulverization process of the raw material drug, but also simplifies the prescription because the obtained preparation does not need to add an antioxidant, and the drug loading amount of the carrier material is high, and the invention has simple production process, easy operation and good reproducibility. .

The celecoxib solid dispersion of the present invention has a weight ratio of the carrier material to the celecoxib, and can be as low as 0.2:1. In the present invention, the higher the content of the carrier material, the easier it is to change the celecoxib from crystal to amorphous, and the higher the bioavailability of the corresponding solid dispersion. In view of the balance between the drug loading amount and the bioavailability, the weight ratio of the carrier material to the celecoxib in the present invention may be from 0.2:1 to 10:1, preferably from 0.3:1 to 5:1, more preferably 0.5. : 1 to 3:1, particularly preferably 0.5:1 to 2:1, most preferably 0.5:1 to 1:1.

In a specific embodiment, the celecoxib solid dispersion of the present invention consists of celecoxib and a carrier material selected from one or more of polyvinylpyrrolidone, copovidone, and crospovidone. Kind. Further, the carrier material is selected from one or more of PVP-K12, PVP-K15, PVP-K17, PVP-K25, PVP-K30, PVP-K60, PVP-K90, PVPP, PVP/VA.

In the carrier material used in the present invention, the type of polyvinylpyrrolidone is not particularly limited, and may be, for example, one or more selected from the group consisting of K12, K15, K17, K25, K30, K60, and K90; Plasdone ^® S-630 is available; crospovidone is available as a commercially available kollidon ^® VA64.

The celecoxib solid dispersion of the present invention can be easily prepared and prepared The method comprises the steps of: dissolving the carrier material and celecoxib in an organic solvent, or dispersing the carrier material in an organic solvent of celecoxib, and removing the organic solvent by vacuum drying or spray drying to obtain a solid dispersion. A step of.

Wherein, the weight ratio of the total weight of the celecoxib and the carrier material to the organic solvent may be from 1:1 to 1:20, preferably from 1:1 to 1:10, more preferably from 1:5 to 1:10.

In a specific embodiment, the celecoxib is completely dissolved in a certain amount of solvent with polyvinylpyrrolidone or copolyvidone, and the solvent is removed by rotary evaporation, dried in a vacuum drying oven, or directly removed by spray drying. That is. The solvent is preferably one or more of methanol, ethanol, acetone, and dichloromethane.

The celecoxib solid dispersion of the present invention can also be obtained in another manner by suspending crospovidone in an organic solvent of celecoxib, stirring for 1 hour, and then removing the solvent by rotary evaporation. It can be obtained by drying in a vacuum drying oven or directly removing the organic solvent by spray drying. The solvent is preferably one or more of methanol, ethanol, acetone, and dichloromethane.

The celecoxib solid dispersion of the present invention can be further prepared into a solid preparation which is a tablet, a pill, a granule, a capsule, and the like. The celecoxib is contained in a unit solid preparation in an amount of 10 mg to 1000 mg. Wherein the solid preparation further comprises a pharmaceutically acceptable excipient, and the excipient may be selected from one or more of a diluent, a disintegrant, a binder, and a lubricant.

Wherein the diluent may be selected from the group consisting of lactose (anhydrous or lactose monohydrate), microcrystalline fiber One or more of vitamins, powdered cellulose, starch, directly compressible starch, calcium hydrogen phosphate, calcium sulfate, calcium hydrogen sulfate, calcium carbonate, mannitol, glucose, etc., and the amount of diluent is the total weight of the solid preparation. 5% to 99%, preferably 10% to 80%.

The disintegrant may be selected from one or more of croscarmellose sodium, sodium carboxymethyl starch, crospovidone, methyl cellulose, pregelatinized starch, sodium alginate, gum, and the like. The disintegrant is used in an amount of from 0.1% to 30%, preferably from 0.2% to 10%, based on the total weight of the solid preparation.

Wherein the binder may be selected from one or more of hydroxypropylmethylcellulose, hydroxypropylcellulose, polyvinylpyrrolidone, starch, sucrose, gum arabic, etc., and the binder is used in an amount of 0.2% by weight of the total weight of the solid preparation. 30%, preferably 0.5% to 10%.

The lubricant may be selected from one or more of stearate, hydrogenated vegetable oil, talc, sodium lauryl sulfate, etc., and the amount of the lubricant is from 0.1% to 10%, preferably 0.1%, based on the total weight of the solid preparation. To 5%.

The solid preparation comprising the solid dispersion of celecoxib of the present invention is prepared by first pulverizing the solid dispersion through a sieve of 60 to 100 mesh, and then molding the desired diluent and/or disintegrating agent with the solid preparation. Mix evenly, add the binder wet granulation, or dry granulation, the prepared granules are dried and sieved, and then uniformly mixed with the lubricant to prepare pellets or granules or compressed or encapsulated; solid dispersion can also be used. The appropriate excipients are directly encapsulated or directly compressed; if desired, the resulting granules or dies or capsules may be further coated. The above and other objects and features of the present invention will become apparent from the accompanying drawings.

The invention is further illustrated by the following examples, which are merely illustrative and are not intended to limit the scope of the invention in any way.

1. Preparation of celecoxib solid dispersion Example 1

formula:

The celecoxib material was prepared according to Chinese patent application CN1141630A.

Preparation:

The raw materials were weighed according to the formula amount, and completely dissolved in ten times of methanol, and the solvent was removed by rotary evaporation, and then dried under reduced pressure in a vacuum drying oven.

Example 2

formula:

Preparation:

The raw materials were weighed according to the formula amount, and completely dissolved in twenty times of ethanol, and the solvent was removed by rotary evaporation, and then dried under reduced pressure in a vacuum drying oven.

Example 3

formula:

Preparation:

The raw materials were weighed according to the formula amount, and completely dissolved in five times the amount of acetone, and the solvent was removed by rotary evaporation, and then dried under reduced pressure in a vacuum drying oven.

Example 4

formula:

Preparation:

The raw materials were weighed according to the formula amount, and completely dissolved in ten times of dichloromethane, and the solvent was removed by rotary evaporation, and then dried under reduced pressure in a vacuum drying oven.

Example 5

formula:

Preparation:

The raw materials were weighed according to the formula amount, and completely dissolved in five times of ethanol, and the solvent was removed by rotary evaporation, and then dried under reduced pressure in a vacuum drying oven.

Example 6

formula:

Preparation:

The celecoxib was weighed according to the formula amount and completely dissolved in a certain amount of ethanol (for the ethanol used, the formulation 22 is ten times the total amount of the original auxiliary materials, and the formula 23 is twice the total amount of the original auxiliary materials). The formulated amount of crospovidone is further added, suspended in the solution, stirred at room temperature for 1 hour, and then the solvent is removed by rotary evaporation, and dried under reduced pressure in a vacuum oven.

2. Preparation of an oral preparation containing a solid dispersion of celecoxib Example 7 Capsules containing celecoxib 200 mg

formula:

Preparation:

The solid dispersion is pulverized and passed through a 80 mesh sieve, and uniformly mixed with lactose, microcrystalline cellulose and croscarmellose sodium, 15% ethanol is used as a wetting agent for wet granulation, and wet granules are dried and granulated with hard fat. After the magnesium acid is mixed evenly, the capsule is obtained.

Example 8 Capsules containing celecoxib 100 mg

formula:

Preparation:

The solid dispersion is pulverized and passed through a 80 mesh sieve, and uniformly mixed with lactose, microcrystalline cellulose and croscarmellose sodium, 15% ethanol is used as a wetting agent for wet granulation, and wet granules are dried and granulated with hard fat. After the magnesium acid is mixed evenly, the capsule is obtained.

Example 9 Capsules containing celecoxib 50 mg

formula:

Preparation:

The solid dispersion is pulverized and passed through a 80 mesh sieve, and uniformly mixed with lactose, microcrystalline cellulose and croscarmellose sodium, 15% ethanol is used as a wetting agent for wet granulation, and wet granules are dried and granulated with hard fat. After the magnesium acid is mixed evenly, the capsule is obtained.

Example 10 Ordinary tablets containing celecoxib 100 mg

formula:

Preparation:

The solid dispersion is pulverized and passed through a 80 mesh sieve, mixed uniformly with microcrystalline cellulose and crospovidone, and granulated by wet method using 15% ethanol as a wetting agent. The wet granules are dried and granulated and mixed with magnesium stearate. After evenly pressing, it is obtained.

Example 11 Film coated tablets containing 50 mg of celecoxib

formula:

Preparation:

The solid dispersion is pulverized and passed through an 80 mesh sieve, mixed uniformly with microcrystalline cellulose and crospovidone, and wet granulated with 15% ethanol as a wetting agent. The wet granules are dried and granulated and uniformly mixed with magnesium stearate. Thereafter, another half amount of crospovidone was added and mixed to prepare a 200 mg plain tablet, which was coated with a white coating of Opadry to obtain a coated tablet containing 50 mg of celecoxib.

Example 12 Film coated tablets containing celecoxib 100 mg

formula:

Preparation:

The solid dispersion is pulverized and passed through an 80 mesh sieve, mixed uniformly with microcrystalline cellulose and crospovidone, and wet granulated with 15% ethanol as a wetting agent. The wet granules are dried and granulated and uniformly mixed with magnesium stearate. Thereafter, another half amount of crospovidone was added and mixed to prepare a 300 mg plain tablet, which was coated with Opadry white coating material to obtain a coated tablet containing 100 mg of celecoxib.

Example 13 Granules containing celecoxib 500 mg

formula:

Preparation:

The solid dispersion was pulverized and passed through a 80 mesh sieve, mixed with microcrystalline cellulose, lactose and crospovidone, and wet granulated with 15% ethanol as a wetting agent. The wet granules were dried and granulated with magnesium stearate. After mixing evenly, the bag is obtained.

Example 14 Granules containing celecoxib 1000 mg

formula:

Preparation:

The solid dispersion was pulverized and passed through a 80 mesh sieve, mixed with microcrystalline cellulose, lactose and crospovidone, and wet granulated with 15% ethanol as a wetting agent. The wet granules were dried and granulated with magnesium stearate. After mixing evenly, the bag is obtained.

Comparative Example 1 Preparation of capsules containing celecoxib 200 mg from uncomminuted celecoxib bulk drug

formula:

Preparation:

The celecoxib bulk drug is uniformly mixed with lactose, croscarmellose sodium and polyvinylpyrrolidone, and is prepared by wet method using a solution of sodium lauryl sulfate as a wetting agent, and the wet granules are dried and granulated. After the magnesium stearate is mixed evenly, the capsule is obtained.

Comparative Example 2

The celecoxib solid dispersion was prepared by using PEG6000 as a carrier, and then prepared into a capsule containing celecoxib 200 mg/particle (patent CN102000018A)

Solid dispersion preparation method: 120 g of PEG6000, 120 g of PEG4000, heated and melted, and 200 g of celecoxib was added and mixed to dissolve a clear solution, followed by rapid cooling and solidification to obtain a solid dispersion containing solid polyethylene glycol (formulation 44).

Capsule formula:

Preparation:

The solid dispersion containing solid polyethylene glycol is pulverized and passed through an 80 mesh sieve, and uniformly mixed with microcrystalline cellulose, propyl gallate and croscarmellose sodium, and made with polyvinylpyrrolidone in ethanol. The binder is prepared by wet method, and the wet granules are dried and granulated, and then mixed with magnesium stearate to form a capsule.

Test Example 1 Powder X-Diffraction

Instrument: Japanese science D/max-3B X-ray diffractometer

test methods:

Solid dispersion formulation 5 (see Figure 3), formulation 17 (see Figure 4), formulation 22 (see Figure 5), celecoxib material (see Figure 1), and celecoxib and poly A suitable amount of the physical mixture of vinylpyrrolidone (see Fig. 2) was recorded on a Cu target, a voltage of 45 kV, and a current of 45 mA. No celecoxib absorption peak was observed in the solid dispersion map, indicating that there was no celecoxib crystal in the obtained solid dispersion, indicating that celecoxib was present in an amorphous state in the solid dispersion, and the solid dispersion was successfully prepared. Therefore, we have surprisingly found that when preparing a solid dispersion of celecoxib, when a relatively small amount of PVP is used as a carrier, a solid dispersion of amorphous form can also be formed, so that polyvinylpyrrolidone and the like have a higher drug loading. the amount.

Test Example 2 Determination of Solubility of Different Carrier Solid Dispersions in Water at 24h

Weigh a certain amount of celecoxib bulk drug and solid dispersion prepared from celecoxib and each hydrophilic carrier in an Erlenmeyer flask, add 100ml of pure water, and shake it for 24 hours in a shaker at 25±2°C. After centrifugation of the solution, the supernatant was taken and its concentration was determined by HPLC.

Preparation of celecoxib and PVP solid dispersion: After celecoxib and PVP were dissolved in absolute ethanol to obtain a clear solution, the solvent was removed by rotary evaporation and dried in a vacuum drying oven under reduced pressure.

Preparation of celecoxib and PEG solid dispersion: After celecoxib is dissolved in molten PEG, it is rapidly cooled and solidified.

Preparation of celecoxib and poloxamer 188 solid dispersion: After celecoxib was dissolved in molten poloxamer 188, it was rapidly cooled and solidified.

Preparation of celecoxib and mannitol solid dispersion: After dissolving celecoxib and mannitol in absolute ethanol to obtain a clear solution, the solvent is removed by rotary evaporation and dried in a vacuum drying oven under reduced pressure.

The solubility of the celecoxib bulk drug in 24h was 0.897 μg/ml, and the solubility of the solid dispersion was as shown in Table 1.

It can be seen that the solid dispersion prepared by using PVP and celecoxib is significantly more soluble than the solid dispersion prepared by using other hydrophilic carriers and celecoxib.

Test Example 3 In vitro dissolution test

Capsule formulations 24 to 28 containing celecoxib solid dispersion and all formulation samples of the comparative examples (formulations 43, 45) and marketed products (Celebrex, Celebrex, celecoxib 200 mg capsules) In vitro dissolution test, the specific operation process is as follows:

Dissolution method: "Chinese Pharmacopoeia" 2010 edition two appendix XD second method paddle method

Dissolution medium: 1.0% sodium lauryl sulfate / 0.04 M trisodium phosphate 1000 ml (pH = 12 ± 0.1)

Speed: 50 rpm

Temperature: 37 ° C

Sampling time: 5, 10, 15, 30, 45, 60 minutes

Determination method: ultraviolet spectrophotometry (comparative comparison method)

Measurement wavelength: 243 nm

The results of in vitro dissolution experiments are shown in Table 2.

It can be seen that the dissolution of the pharmaceutical compositions of the formulations of Examples 7 to 28 of the present invention is significantly better than that of the pharmaceutical composition of the comparative example 1 raw material which is not pulverized, and is superior to the marketed preparation, and is also superior to polyethylene glycol. Comparative Example 2 of Carrier Material The dissolution of the pharmaceutical composition. In addition, we have also surprisingly found that the solid dispersion prepared from polyvinylpyrrolidone as a carrier material can achieve a better dissolution effect when the carrier material used is significantly lower than that of polyethylene glycol. The drug loading of vinylpyrrolidone is large.

Test Example 4 Accelerated Stability Test

The product of Example 7 - Formulation 25, Example 7 - Formulation 28 and Comparative Example 2 - Formulation 45 were wrapped in an aluminum-plastic blister, wrapped in an aluminum foil bag, and placed in a constant temperature and humidity chamber (constant temperature 40 ° C ± 1 ° C, Constant humidity RH75%±2.5%), placed continuously for 6 months, samples were taken at the end of the first, second, third, and sixth months. The results are shown in Table 3.

The results showed that the pharmaceutical composition of the present invention had been substantially accelerated since the accelerated test for 6 months, and the properties of the pharmaceutical composition were stable, and it was stable compared with Comparative Example 2 even without the addition of the antioxidant.

Test Example 5 Bioavailability and Bioequivalence Test

Reference preparation (commercial celecoxib capsule, Celebrex, Pfizer, 200 mg/granule), test preparation 1 (capsule prepared in Formulation 25 of Example 7, 200 mg/granule), test preparation 2 (Prepared by Formulation 28 in Example 7 Capsules, 200mg/particle) were tested for bioavailability and bioequivalence in Beagle dogs. The specific operation procedure is as follows:

Test items: 12 Beagle dogs, half male and half female, and the Beagle dog weighed 9.54 ± 0.45 kg.

Test protocol: 12 Beagle dogs were randomly divided into three groups, 4 in each group, cross-administered, fasted 12 hours before the test, and free to drink water. Three groups of Beagle dogs were given 10 mg/kg comparative preparation, 10 mg/kg test preparation 1 and 10 mg/kg test preparation 2, and 0.25, 0.5, 0.75, 1, 2, 4, 8, 12, 24 h veins were collected before and after administration. blood. The plasma samples were separated and analyzed by high performance liquid chromatography, and the blood drug concentration data were obtained for DAS software analysis.

The measurement results are shown in Table 4.

As can be seen from the above, the pharmaceutical composition of the present invention (Formulation 25 of Example 7 and Formulation 28 of Example 7) reached the maximum blood drug concentration time (Tmax), which was significantly faster than the comparative preparation (marketed preparation), the maximum blood of celecoxib. Drug concentration (Cmax) and bioavailability (AUC) were also significantly higher than the comparative formulations, slightly higher than the data of Comparative Example 2.

in conclusion:

In the present invention, the solid dispersion of celecoxib prepared by using polyvinylpyrrolidone as a carrier material has higher drug loading and better stability than the solid dispersion prepared by using polyethylene glycol as a carrier material. The dissolution rate and bioavailability of the traditional Chinese medicine composition of the present invention are higher than those of the marketed products.

Figure 1 is a powder X-ray diffraction pattern of celecoxib starting material.

Figure 2 is a powder X-ray pattern of a physical mixture of celecoxib and polyvinylpyrrolidone (1:0.2).

Figure 3 is a powder X-ray pattern of a solid dispersion of celecoxib and polyvinylpyrrolidone (1:0.2).

Figure 4 is a powder X-ray pattern of a solid dispersion of celecoxib and copovidone (1:0.2).

Figure 5 is a powder X-ray pattern of a solid dispersion of celecoxib and crospovidone (1:0.5).

Since the picture in this case is the number of tests, it is not a representative figure of this case.

Therefore, there is no designated representative map in this case.

Claims (17)

A solid dispersion of celecoxib, wherein the solid dispersion comprises celecoxib and a carrier material selected from one or more of polyvinylpyrrolidone, copovidone, and crospovidone. The solid dispersion of celecoxib according to claim 1, wherein the weight ratio of the carrier material to celecoxib is not less than 0.2:1. The solid dispersion of celecoxib according to claim 1 or 2, wherein the weight ratio of the carrier material to celecoxib is from 0.2:1 to 10:1. The solid dispersion of celecoxib according to claim 3, wherein the weight ratio of the carrier material to celecoxib is from 0.3:1 to 5:1. The solid dispersion of celecoxib according to claim 4, wherein the weight ratio of the carrier material to celecoxib is from 0.5:1 to 3:1. The solid dispersion of celecoxib according to claim 5, wherein the weight ratio of the carrier material to celecoxib is from 0.5:1 to 2:1. The solid dispersion of celecoxib according to claim 6, wherein the weight ratio of the carrier material to celecoxib is from 0.5:1 to 1:1. The celecoxib solid dispersion of any one of claims 1 to 7 wherein the celecoxib solid dispersion consists of celecoxib and a carrier material. The celecoxib solid dispersion according to any one of claims 1 to 8, wherein the carrier material is selected from the group consisting of PVP-K12, PVP-K15, PVP-K17, PVP-K25, PVP-K30, One or more of PVP-K60, PVP-K90, PVPP, PVP/VA. A method of preparing the solid dispersion of celecoxib according to any one of claims 1 to 9, which comprises dissolving a carrier material and celecoxib in an organic solvent, or dispersing the carrier material in a dispersion In the organic solvent of celecoxib, the organic solvent is removed by vacuum drying or spray drying to obtain a solid dispersion. The method of preparing a solid dispersion of celecoxib according to claim 10, wherein the weight ratio of the total weight of the celecoxib and the carrier material to the organic solvent is from 1:1 to 1:20. The method for preparing a solid dispersion of celecoxib according to claim 11, wherein the weight ratio of the total weight of the celecoxib and the carrier material to the organic solvent is from 1:1 to 1:10. The method of preparing a solid dispersion of celecoxib according to claim 11, wherein the weight ratio of the total weight of the celecoxib and the carrier material to the organic solvent is from 1:5 to 1:10. A method of preparing a solid dispersion of celecoxib as described in claim 10 or 11, wherein the organic solvent is one or more selected from the group consisting of methanol, ethanol, acetone, and dichloromethane. A solid preparation of celecoxib comprising the solid dispersion of celecoxib according to any one of claims 1 to 9, wherein the solid preparation is a tablet, a pill, a granule or a capsule. The solid preparation of celecoxib according to claim 15, which further comprises a pharmaceutically acceptable excipient selected from the group consisting of a diluent, a disintegrant, a binder, and a lubricant. Or several. a solid preparation of celecoxib according to claim 16 of the patent application, The content of the celecoxib in the unit solid preparation is 10 mg to 1000 mg; the amount of the diluent is 5% to 99% of the total weight of the solid preparation; the amount of the disintegrant is 0.1% to 30% of the total weight of the solid preparation; the binder The amount is from 0.2% to 30% by weight based on the total weight of the solid preparation; and the amount of the lubricant is from 0.1% to 10% by weight based on the total weight of the solid preparation.