CN107898787A - A kind of pharmaceutical composition and its preparation and preparation method - Google Patents
A kind of pharmaceutical composition and its preparation and preparation method Download PDFInfo
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- CN107898787A CN107898787A CN201711362158.3A CN201711362158A CN107898787A CN 107898787 A CN107898787 A CN 107898787A CN 201711362158 A CN201711362158 A CN 201711362158A CN 107898787 A CN107898787 A CN 107898787A
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/444—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2009—Inorganic compounds
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
- A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2886—Dragees; Coated pills or tablets, e.g. with film or compression coating having two or more different drug-free coatings; Tablets of the type inert core-drug layer-inactive layer
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Abstract
The present invention relates to drug field, specifically, is related to a kind of pharmaceutical composition and its preparation and preparation method.Contain Etoricoxib in the pharmaceutical composition of the present invention, the size distribution of Etoricoxib is：D90≤30μm.The present invention controls the granularity of Etoricoxib in a specific range, so as to significantly improve the dissolution rate of drug regimen of the present invention.
Description
Technical field
The present invention relates to drug field, specifically, is related to a kind of pharmaceutical composition and its preparation and preparation method.
Background technology
Etoricoxib (Etoricoxib) is a kind of high selectivity Transitional cell carcinomas (COX-2) inhibitor, chemical name：[5-
Chloro- 2- (6- picoline -3- bases) -3- (4- sulfonyloxy methyls phenyl) pyridine], its structural formula is as follows：
Etoricoxib has anti-inflammatory, brings down a fever and analgesic effect, suitable for treatment osteoarthritis acute stage and chronic phase
Sings and symptoms, can also treat acute gouty arthritis.Etoricoxib is by American society of rheumatism gout diagnosis and treatment guide
Treatment of the recommendation for acute gouty arthritis, China's osteoarthritis diagnosis and treatment guide and osteology branch of Chinese Medical Association
Orthopedic Pain processing expert opinion also recommends to have the patient of intestines and stomach risk to use Selective COX-2 inhibitor, can be selected and relies on
Examine former times.
The poorly water-soluble of Etoricoxib raw material, solubility is small, and the dissolution rate for being prepared into medicine after preparation is relatively low.Chinese patent
CN200580037915 discloses a kind of method for the granular preparations for oral administration for preparing etoricoxib.Chinese patent
CN201410212618 opens a kind of Etoricoxib piece, includes Etoricoxib 3~30%, microcrystalline cellulose 10%~40%, vertical compression
Lactose 40%~80%, pregelatinized starch 5%~5%, povidone 1%~10%, sodium carboxymethyl starch 1%~10% and tristearin
Sour magnesium 0.5%~3%.Chinese patent 201510724220.3 discloses a kind of pharmaceutical composition containing Etoricoxib, the medicine
Contain 10% (weight) -40% (weight) Etoricoxib, 3% (weight) -25% (weight) disintegrant and other medicines in composition
Acceptable excipient on.Disintegrant may be selected from starch, Ac-Di-Sol, sodium carboxymethyl starch, the poly- dimension of crosslinking
One or more in ketone, low-substituted hydroxypropyl cellulose, povidone, microcrystalline cellulose.But fail effectively to solve support to examine
The problem of former times dissolution rate.
The poorly water-soluble of Etoricoxib raw material, solubility are small.Belong to 2 class of Biopharmaceutics Classification, low molten hypertonic medicine.
In order to improve bioavilability, generally require and crushing operation is carried out to the API of medicine, to reduce particle diameter increase body absorption.Powder
Tablet prepared by last direct tablet compressing is although easy to operate, but the risk for the less raw material of particle diameter there are mixture homogeneity.By
There is chance water or alcohol in raw material can turn brilliant phenomenon, so being had difficulties using tablet prepared by wet granulation.
The present invention provides a kind of pharmaceutical composition containing Etoricoxib and preparation method thereof, this method is examined using support
Former times crystal form is V, using dry granulation process, adds specific disintegrant and solubilizer, effectively facilitates medicine disintegration dissolution, is improved
Bioavilability, while dry granulation reduces the energy consumption of drying process, auxiliary material used is simple and easy to get, and simple production process, has
Effect reduces production cost.
The content of the invention
The first invention purpose of the present invention is to propose a kind of pharmaceutical composition.
The second goal of the invention of the present invention is to propose the preparation containing the pharmaceutical composition.
The 3rd goal of the invention of the present invention is the preparation method for proposing said preparation.
In order to complete the purpose of the present invention, the technical solution that uses for：
First aspect present invention proposes a kind of pharmaceutical composition, containing Etoricoxib, disintegrant, filler, lubricant and
Other pharmaceutically acceptable auxiliary materials；Wherein, the size distribution of the Etoricoxib is：D90≤30μm.
Wherein, D90 refers to the cumulative particle sizes distribution number of Etoricoxib and reaches granularity corresponding when 90%, that is, is less than or equal to
30 μm of particle accounts for 90%.The present invention has found through sharp study, within the range the pharmaceutical composition of the Etoricoxib of granularity
Dissolution rate is significantly improved, so as to improve the bioavilability of Etoricoxib.
Further, which includes 10% (weight) -30% (weight) Etoricoxib, 2% (weight) -6% (weight
Amount) disintegrant, 53% (weight) -80% (weight) filler, 0.75% (weight) -4% (weight) lubricant and other pharmacy
Upper acceptable auxiliary material；Wherein, the size distribution of the Etoricoxib is：D90≤30 μm, D50≤10 μm, D10≤5 μm；
That is, the particle that Etoricoxib is less than between 30 μm accounts for 90%, and the particle less than 10 μm accounts for 50%, less than 5 μm
Grain accounts for 10%.Etoricoxib of the embodiment of the present invention can also improve mixture homogeneity of the medicament powder in preparation process.
10% (weight) -30% (weight) Etoricoxib, 2% (weight are included in the pharmaceutical composition of the embodiment of the present invention
Amount) -6% (weight) disintegrant, 53% (weight) -80% (weight) filler, 0.75% (weight) -4% (weight) lubricant
And other pharmaceutically acceptable auxiliary materials.Compared with the Etoricoxib pharmaceutical composition in prior art, in the embodiment of the present invention
Disintegrant dosage reduce.
Further, the disintegrant is Ac-Di-Sol.Ac-Di-Sol is met water and is disintegrated rapidly,
As the disintegration rate that main ingredient is effectively facilitated for disintegrant.Also, sodium atom and bulk pharmaceutical chemicals in Ac-Di-Sol
Oxygen atom in Etoricoxib by chemical bond and, stable space structure can be manageed it into, ensure that the stability of main ingredient, so as to
Further improve the stability of tablet.
Further, the weight ratio of the Etoricoxib and disintegrant is 20: 1-5: 1, wherein it is preferred that 20: 1.
Further, the filler is the one or more in Lactis Anhydrous, microcrystalline cellulose and calcium phosphate dibasic anhydrous.
Further, the lubricant is magnesium stearate.
Further, the crystal form of the Etoricoxib is crystal form V.
The present invention provides a kind of preparation method of Etoricoxib granularity,
The size distribution of the Etoricoxib is：The preparation method of D90≤30 μm is：
S1：A part of filler and Etoricoxib is taken to grind 30-60min after mixing, the Etoricoxib and filler
Mass ratio is 3: 1-1: 1；
S2：Powder after grinding is input in airslide disintegrating mill by dry nitrogen, obtains the mixed-powder of D90≤100 μm
I；Wherein, feed speed is 4.0-6.0kg/h, 1 × 105-5 of air pressure × 105Pa；
S3：Take S2 mixed-powder and grinding after disintegrant be uniformly mixed, airslide disintegrating mill is input to by dry nitrogen
In, the mixed-powder II of acquisition D90≤30 μm；Wherein, feed speed is 1.0-3.0kg/h, air pressure 1 × 105-5×105Pa。
Etoricoxib in the embodiment of the present invention in the range of the specified particle size can be prepared by the method for micronizing, be led to
Cross that the Etoricoxib form that is prepared of micronizing is homogeneous, and surface is smooth, and added in preparation process specific disintegrant and
Filler, is added without plus solvent, avoids the phenomenon for meeting water or alcohol Etoricoxib turn crystalline substance, and particle diameter diminishes what the uniformity was deteriorated
Problem, is more conducive to the mixture homogeneity for improving medicament powder in preparation process.
Second aspect of the present invention proposes a kind of preparation, the pharmaceutical composition containing above-mentioned first aspect, specifically, the system
Agent is tablet.
Third aspect present invention proposes a kind of method for preparing tablet thereof of described pharmaceutical composition, comprises the following steps：
1) just mix：Recipe quantity mixed-powder II, filler are uniformly mixed, the lubricant ground and mixed added in adding,
Obtain mixtures III；
2) pelletize：Mixtures III is pelletized by dry granulating machine to obtain mixture IV；
3) it is total mixed：It is uniform that mixture IV adds additional mix lubricant；
4) tabletting：Φ 10mm scrobicula stampings, hardness range are controlled in 80-130N；
5) it is coated：Coating solution is prepared in the ratio of 12% (w/w), coating to weightening is 3%-5%.
The hardness range of tablet of the embodiment of the present invention is controlled in 80N~130N, and in the hardness range, not only tablet is fully full
The requirement of sufficient embrittlement degree, will not crush, sliver in storage and transportational process, and further ensure that the disintegration of tablet
Speed.
The preparation method of the embodiment of the present invention uses dry granulation, effectively reduces the energy consumption of drying process, production technology
Simply, production cost is effectively reduced.And brilliant phenomenon can be turned in the presence of water or alcohol is met by avoiding raw material in wet-granulation process
The problem of.
Optionally, preparation method further includes the step of coating, it is preferred that the scope of coating weight gain is 2%~4%.
Existing coating formula of liquid can be selected in the coating solution of the embodiment of the present invention.
The technical scheme attainable technique effect of institute at least that：
Etoricoxib crystal form is used as V, using ultra micro dusting and dry granulation process, adds specific disintegrant and solubilising
Agent, effectively facilitates medicine disintegration dissolution, improves bioavilability, while plus solvent is added without in preparation engineering, avoids chance
Water or alcohol Etoricoxib turn brilliant phenomenon, and particle diameter diminishes uniformity the problem of being deteriorated, and dry granulation reduce it is dried
The energy consumption of journey, auxiliary material used is simple and easy to get, and simple production process, effectively reduces production cost.
Embodiment
With reference to specific embodiment, the present invention is further explained.It is to be understood that these embodiments are merely to illustrate the present invention
Rather than limit the scope of the invention.
The embodiment of the present invention proposes a kind of pharmaceutical composition, and containing Etoricoxib, the size distribution of Etoricoxib is：D90
≤30μm。
Embodiment 1
The composition of pharmaceutical composition is as shown in table 1：
Table 1
The size distribution of Etoricoxib is：The preparation method of D90≤30 μm is：
S1：Filler 120g and Etoricoxib 120g is taken to grind 60min after mixing；
S2：Powder after grinding is input in airslide disintegrating mill by dry nitrogen, obtains the mixed-powder of D90≤100 μm
I；Wherein, feed speed is 4.0kg/h, air pressure 5 × 105Pa；
S3：Take S2 mixed-powder and grinding after disintegrant 6g be uniformly mixed, air-flow crushing is input to by dry nitrogen
In machine, the mixed-powder II of D90≤30 μm is obtained；Wherein, feed speed is 1.0kg/h, air pressure 3 × 105Pa。
Wherein, filler is 200g Lactis Anhydrouses and the homogeneous mixture of 70g microcrystalline celluloses；Disintegrant is crosslinking carboxylic first
Base sodium cellulosate；
Method for preparing tablet thereof：
1) just mix：Above-mentioned mixed-powder II and 150g fillers are uniformly mixed, the lubricant 2.2g grindings added in adding
Mixing, obtains mixtures III；
2) pelletize：Mixtures III is pelletized by dry granulating machine to obtain mixture IV；
3) it is total mixed：Mixture IV adds additional lubricant 2.2g and is uniformly mixed；
4) tabletting：Φ 10mm scrobicula stampings, hardness range are controlled in 100N；
5) it is coated：Coating solution is prepared in the ratio of 12% (w/w), coating to weightening is 4%.
Wherein, filler is 200g Lactis Anhydrouses and the homogeneous mixture of 70g microcrystalline celluloses；Lubricant is stearic acid
Magnesium；Coating solution is the Opadry II solution that mass percent concentration is 12%.
Embodiment 2
The composition of pharmaceutical composition is as shown in table 2：
Table 2
The size distribution of Etoricoxib is：The preparation method of D90≤30 μm is：
S1：Filler 60g and Etoricoxib 120g is taken to grind 45min after mixing；
S2：Powder after grinding is input in airslide disintegrating mill by dry nitrogen, obtains the mixed-powder of D90≤100 μm
I；Wherein, feed speed is 5.0kg/h, air pressure 4 × 105Pa；
S3：Take S2 mixed-powder and grinding after disintegrant 15g be uniformly mixed, air-flow crushing is input to by dry nitrogen
In machine, the mixed-powder II of D90≤30 μm is obtained；Wherein, feed speed is 2.0kg/h, air pressure 2 × 105Pa。
Wherein, filler is 100g calcium phosphate dibasic anhydrouses and the homogeneous mixture of 170g microcrystalline celluloses；Disintegrant is friendship
Join sodium carboxymethylcellulose；
Method for preparing tablet thereof：
1) just mix：Above-mentioned mixed-powder II and 210g fillers are uniformly mixed, the lubricant 2.4g grindings added in adding
Mixing, obtains mixtures III；
2) pelletize：Mixtures III is pelletized by dry granulating machine to obtain mixture IV；
3) it is total mixed：Mixture IV adds additional lubricant 2.0g and is uniformly mixed；
4) tabletting：Φ 10mm scrobicula stampings, hardness range are controlled in 130N；
5) it is coated：Coating solution is prepared in the ratio of 12% (w/w), coating to weightening is 5%.
Wherein, filler is 100g calcium phosphate dibasic anhydrouses and the homogeneous mixture of 170g microcrystalline celluloses；Lubricant is hard
Fatty acid magnesium；Coating solution is the Opadry II solution that mass percent concentration is 12%.
Embodiment 3
The composition of pharmaceutical composition is as shown in table 3：
Table 3
The size distribution of Etoricoxib is：The preparation method of D90≤30 μm is：
S1：Filler 40g and Etoricoxib 120g is taken to grind 30min after mixing；
S2：Powder after grinding is input in airslide disintegrating mill by dry nitrogen, obtains the mixed-powder of D90≤100 μm
I；Wherein, feed speed is 6.0kg/h, air pressure 3 × 105Pa；
S3：Take S2 mixed-powder and grinding after disintegrant 24g be uniformly mixed, air-flow crushing is input to by dry nitrogen
In machine, the mixed-powder II of D90≤30 μm is obtained；Wherein, feed speed is 3.0kg/h, air pressure 5 × 105Pa。
Wherein, filler is 200g Lactis Anhydrouses and the homogeneous mixture of 70g microcrystalline celluloses；Disintegrant is crosslinking carboxylic first
Base sodium cellulosate；
Method for preparing tablet thereof：
1) just mix：Above-mentioned mixed-powder II and 230g fillers are uniformly mixed, the lubricant 2.2g grindings added in adding
Mixing, obtains mixtures III；
2) pelletize：Mixtures III is pelletized by dry granulating machine to obtain mixture IV；
3) it is total mixed：Mixture IV adds additional lubricant 2.2g and is uniformly mixed；
4) tabletting：Φ 10mm scrobicula stampings, hardness range are controlled in 80N；
5) it is coated：Coating solution is prepared in the ratio of 12% (w/w), coating to weightening is 3%.
Wherein, filler is 200g Lactis Anhydrouses and the homogeneous mixture of 70g microcrystalline celluloses；Lubricant is stearic acid
Magnesium；Coating solution is the Opadry II solution that mass percent concentration is 12%.
Embodiment 4
The composition of pharmaceutical composition is as shown in table 4：
Table 4
The size distribution of Etoricoxib is：The preparation method of D90≤30 μm is：
S1：Filler 60g and Etoricoxib 120g is taken to grind 40min after mixing；
S2：Powder after grinding is input in airslide disintegrating mill by dry nitrogen, obtains the mixed-powder of D90≤100 μm
I；Wherein, feed speed is 5.0kg/h, air pressure 4 × 105Pa；
S3：Take S2 mixed-powder and grinding after disintegrant 6g be uniformly mixed, air-flow crushing is input to by dry nitrogen
In machine, the mixed-powder II of D90≤30 μm is obtained；Wherein, feed speed is 2.0kg/h, air pressure 2 × 105Pa。
Wherein, filler is 100g calcium phosphate dibasic anhydrouses and the homogeneous mixture of 170g microcrystalline celluloses；Disintegrant is friendship
Join sodium carboxymethylcellulose；
Method for preparing tablet thereof：
1) just mix：Above-mentioned mixed-powder II and 210g fillers are uniformly mixed, the lubricant 2.4g grindings added in adding
Mixing, obtains mixtures III；
2) pelletize：Mixtures III is pelletized by dry granulating machine to obtain mixture IV；
3) it is total mixed：Mixture IV adds additional lubricant 2.0g and is uniformly mixed；
4) tabletting：Φ 10mm scrobicula stampings, hardness range are controlled in 130N；
5) it is coated：Coating solution is prepared in the ratio of 12% (w/w), coating to weightening is 5%.
Wherein, filler is 100g calcium phosphate dibasic anhydrouses and the homogeneous mixture of 170g microcrystalline celluloses；Lubricant is hard
Fatty acid magnesium；Coating solution is the Opadry II solution that mass percent concentration is 12%.
Embodiment 5
The composition of pharmaceutical composition is as shown in table 5：
Table 5
The size distribution of Etoricoxib is：The preparation method of D90≤30 μm is：
S1：Filler 80g and Etoricoxib 120g is taken to grind 45min after mixing；
S2：Powder after grinding is input in airslide disintegrating mill by dry nitrogen, obtains the mixed-powder of D90≤100 μm
I；Wherein, feed speed is 5.0kg/h, air pressure 4 × 105Pa；
S3：Take S2 mixed-powder and grinding after disintegrant 6g be uniformly mixed, air-flow crushing is input to by dry nitrogen
In machine, the mixed-powder II of D90≤30 μm is obtained；Wherein, feed speed is 2.0kg/h, air pressure 2 × 105Pa。
Wherein, filler is 200g calcium phosphate dibasic anhydrouses and the homogeneous mixture of 70g microcrystalline celluloses；Disintegrant is crosslinking
Sodium carboxymethylcellulose；
Method for preparing tablet thereof：
1) just mix：Above-mentioned mixed-powder II and 190g fillers are uniformly mixed, the lubricant 2.2g grindings added in adding
Mixing, obtains mixtures III；
2) pelletize：Mixtures III is pelletized by dry granulating machine to obtain mixture IV；
3) it is total mixed：Mixture IV adds additional lubricant 2.2g and is uniformly mixed；
4) tabletting：Φ 10mm scrobicula stampings, hardness range are controlled in 120N；
5) it is coated：Coating solution is prepared in the ratio of 12% (w/w), coating to weightening is 4%.
Wherein, filler is 200g calcium phosphate dibasic anhydrouses and the homogeneous mixture of 70g microcrystalline celluloses；Lubricant is tristearin
Sour magnesium；Coating solution is the Opadry II solution that mass percent concentration is 12%.
Embodiment 6
The composition of pharmaceutical composition is as shown in table 6：
Table 6
The size distribution of Etoricoxib is：The preparation method of D90≤30 μm is：
S1：Filler 100g and Etoricoxib 120g is taken to grind 45min after mixing；
S2：Powder after grinding is input in airslide disintegrating mill by dry nitrogen, obtains the mixed-powder of D90≤100 μm
I；Wherein, feed speed is 5.0kg/h, 4 × 105Pa of air pressure；
S3：Take S2 mixed-powder and grinding after disintegrant 6g be uniformly mixed, air-flow crushing is input to by dry nitrogen
In machine, the mixed-powder II of D90≤30 μm is obtained；Wherein, feed speed is 2.0kg/h, 2 × 105Pa of air pressure.
Wherein, filler is the homogeneous mixture of 50g calcium phosphate dibasic anhydrouses, 50g Lactis Anhydrouses and 170g microcrystalline celluloses；
Disintegrant is Ac-Di-Sol；
Method for preparing tablet thereof：
1) just mix：Above-mentioned mixed-powder II and 170g fillers are uniformly mixed, the lubricant 2.4g grindings added in adding
Mixing, obtains mixtures III；
2) pelletize：Mixtures III is pelletized by dry granulating machine to obtain mixture IV；
3) it is total mixed：Mixture IV adds additional lubricant 2.0g and is uniformly mixed；
4) tabletting：Φ 10mm scrobicula stampings, hardness range are controlled in 100N；
5) it is coated：Coating solution is prepared in the ratio of 12% (w/w), coating to weightening is 4%.
Wherein, filler is the homogeneous mixture of 50g calcium phosphate dibasic anhydrouses, 50g Lactis Anhydrouses and 170g microcrystalline celluloses；
Lubricant is magnesium stearate；Coating solution is the Opadry II solution that mass percent concentration is 12%.
Comparative example 1
The composition of pharmaceutical composition is as shown in table 7：
Table 7
Method for preparing tablet thereof：
(1) weigh：The Ac-Di-Sol and 70g that add in 120g Etoricoxibs, 200g Lactis Anhydrouses, 6g is micro-
Crystalline cellulose mixes, and adds the interior 2.2g magnesium stearates mixing added, obtains mixture I；
(2) pelletize：Mixture I is pelletized with dry granulating machine, obtains Etoricoxib medicament composition granule；
(3) it is total mixed：Etoricoxib medicament composition granule adds magnesium stearate 2.2g and is uniformly mixed；
(4) tabletting：Φ 10mm scrobicula stampings, hardness range control 100N；
(5) it is coated：Coating solution is prepared in the ratio of 12% (w/w), coating to weightening is 4%.
Coating solution is the Opadry II solution that mass percent concentration is 12%.
Comparative example 2
The composition of pharmaceutical composition is as shown in table 8：
Table 8
The size distribution of Etoricoxib is：The preparation method of D90≤30 μm is：
Etoricoxib is input in airslide disintegrating mill by dry nitrogen, obtains the mixed-powder of D90≤30 μm；
Method for preparing tablet thereof：
(1) weigh：The Ac-Di-Sol and 70g that add in 120g Etoricoxibs, 200g Lactis Anhydrouses, 6g is micro-
Crystalline cellulose mixes, and adds the interior 2.2g magnesium stearates mixing added, obtains mixture I；
(2) pelletize：Mixture I is pelletized with dry granulating machine, obtains Etoricoxib medicament composition granule；
(3) it is total mixed：Etoricoxib medicament composition granule adds magnesium stearate 2.2g and is uniformly mixed；
(4) tabletting：Φ 10mm scrobicula stampings, hardness range control 100N；
(5) it is coated：Coating solution is prepared in the ratio of 12% (w/w), coating to weightening is 4%.
Coating solution is the Opadry II solution that mass percent concentration is 12%.
Comparative example 3
The composition of pharmaceutical composition is as shown in table 9：
Table 9
The size distribution of Etoricoxib is：The preparation method of D90≤30 μm is：
S1：Filler 120g and Etoricoxib 120g is taken to grind 60min after mixing；
S2：Powder after grinding is input in airslide disintegrating mill by dry nitrogen, obtains the mixed-powder of D90≤100 μm
I；Wherein, feed speed is 4.0kg/h, air pressure 5 × 105Pa；
S3：Take S2 mixed-powder and grinding after disintegrant 6g be uniformly mixed, air-flow crushing is input to by dry nitrogen
In machine, the mixed-powder II of D90≤30 μm is obtained；Wherein, feed speed is 1.0kg/h, air pressure 3 × 105Pa。
Wherein, filler is 200g Lactis Anhydrouses and the homogeneous mixture of 70g microcrystalline celluloses；Disintegrant is crosslinking carboxylic first
Base sodium cellulosate；
Method for preparing tablet thereof：
1) just mix：Above-mentioned mixed-powder II and 150g fillers are uniformly mixed, the lubricant 2.2g grindings added in adding
Mixing, obtains mixtures III；
2) pelletize：Mixtures III is pelletized by dry granulating machine to obtain mixture IV；
3) it is total mixed：Mixture IV adds additional lubricant 2.2g and is uniformly mixed；
4) tabletting：Φ 10mm scrobicula stampings, hardness range are controlled in 100N；
5) it is coated：Coating solution is prepared in the ratio of 12% (w/w), coating to weightening is 4%.
Wherein, filler is 200g Lactis Anhydrouses and the homogeneous mixture of 70g microcrystalline celluloses；Lubricant is hydrogenated vegetable
Oil；Coating solution is the Opadry II solution that mass percent concentration is 12%.
Comparative example 4
The composition of pharmaceutical composition is as shown in table 10：
Table 10
The size distribution of Etoricoxib is：The preparation method of D90≤30 μm is：
S1：Filler 120g and Etoricoxib 120g is taken to grind 60min after mixing；
S2：Powder after grinding is input in airslide disintegrating mill by dry nitrogen, obtains the mixed-powder of D90≤100 μm
I；Wherein, feed speed is 4.0kg/h, air pressure 5 × 105Pa；
S3：Take S2 mixed-powder and grinding after disintegrant 6g be uniformly mixed, air-flow crushing is input to by dry nitrogen
In machine, the mixed-powder II of D90≤30 μm is obtained；Wherein, feed speed is 1.0kg/h, air pressure 3 × 105Pa。
Wherein, filler is 200g Lactis Anhydrouses and the homogeneous mixture of 70g microcrystalline celluloses；Disintegrant is dried starch；
Method for preparing tablet thereof：
1) just mix：Above-mentioned mixed-powder II and 150g fillers are uniformly mixed, the lubricant 2.2g grindings added in adding
Mixing, obtains mixtures III；
2) pelletize：Mixtures III is pelletized by dry granulating machine to obtain mixture IV；
3) it is total mixed：Mixture IV adds additional lubricant 2.2g and is uniformly mixed；
4) tabletting：Φ 10mm scrobicula stampings, hardness range are controlled in 100N；
5) it is coated：Coating solution is prepared in the ratio of 12% (w/w), coating to weightening is 4%.
Wherein, filler is 200g Lactis Anhydrouses and the homogeneous mixture of 70g microcrystalline celluloses；Lubricant is stearic acid
Magnesium；Coating solution is the Opadry II solution that mass percent concentration is 12%.
Embodiment 7
The tablet prepared by embodiment and comparative example is measured according to the second method of dissolution rate in pharmacopeia in 2015.
The tablet being prepared is detected into dissolution rate under the same conditions.Obtained experimental result is as shown in table 11：
Table 11
Comparative example 1 is is not defined Etoricoxib particle diameter, manufactured tablet；Comparative example 2 is individually to Etoricoxib
Granularity is handled, manufactured tablet；Comparative example 3 is changes lubricant, and other conditions are constant, manufactured tablet；Comparative example 4 is
Change disintegrant, manufactured tablet；
By the Dissolution experiments of table 11, the Etoricoxib of the granularity obtained using the specific preparation method of the present invention is equal
The dissolution rate of tablet is remarkably improved, the dissolution rate without being defined to Etoricoxib granularity is substantially very low；Individually to relying on
Examine former times granularity to be defined and be added without filler and disintegrant, dissolution rate decrease to some degree；Change disintegrant and profit
Lubrication prescription has solubility larger negatively influencing.
Embodiment 8
Uniformity of dosage units and assay are carried out to 10 batches of samples according to official method.
The sign content (X) of every：
Averagely represent content
The absolute value (A) of the difference of labelled amount and average：
Standard deviation (S)：
Criterion：1. such as A+1.80S≤15.0, then the uniformity of dosage units of test sample meets regulation.If 2. A+S ＞ 15.0,
It is against regulation.If 3. A+1.80S ＞ 15.0, and A+S≤15.0, then it should separately take 20 retrials.
According to first, retrial as a result, calculating the average X of 30, the absolute value A of the difference of standard deviation S and labelled amount；Such as A+
1.45S≤15.0, then the uniformity of dosage units of test sample meet regulation；If A=1.45 ＞ 15.0, against regulation.
The uniformity of dosage units of above-mentioned tablet is measured according to States Pharmacopoeia specifications, obtained experimental result is as shown in table 12：
Table 12
Comparative example 1 is is not defined Etoricoxib particle diameter, manufactured tablet；Comparative example 2 is individually to Etoricoxib
Granularity is handled, manufactured tablet；Comparative example 3 is changes lubricant, and other conditions are constant, manufactured tablet；Comparative example 4 is
Change disintegrant, manufactured tablet；
Tested by the uniformity of dosage units of table 12, the uniformity of dosage units of the tablet obtained using this method is significantly higher than
Comparative example；2 uniformity of dosage units of comparative example is obvious.
The dissolution rate and uniformity of dosage units for the tablet that the present invention is prepared are substantially better than comparative example, illustrate that the present invention is each
Component collocation is reasonable, and preparation process design is reasonable, indispensable, and the tablet that this specific combination is formed, generates obvious
Synergistic function.It is not for limiting claim, any ability although the present invention is disclosed as above with preferred embodiment
Field technique personnel without departing from the inventive concept of the premise, can make some possible variations and modification, therefore this hair
Bright protection domain should be accurate with scope that the claims in the present invention are defined.
Claims (10)
1. a kind of pharmaceutical composition, it is characterised in that contain Etoricoxib, disintegrant, filler, profit in described pharmaceutical composition
Lubrication prescription and other pharmaceutically acceptable auxiliary materials；Wherein, the size distribution of the Etoricoxib is：D90≤30μm.
2. pharmaceutical composition according to claim 1, it is characterised in that the pharmaceutical composition include 10% (weight)-
30% (weight) Etoricoxib, 2% (weight) -6% (weight) disintegrant, 53% (weight) -80% (weight) filler,
0.75% (weight) -4% (weight) lubricant and other pharmaceutically acceptable auxiliary materials；Wherein, the granularity of the Etoricoxib
It is distributed as：
D90≤30 μm, D50≤10 μm, D10≤5 μm.
3. pharmaceutical composition according to claim 1, it is characterised in that the disintegrant is cross-linked carboxymethyl cellulose
Sodium.
4. pharmaceutical composition according to claim 1, it is characterised in that the weight ratio of the Etoricoxib and disintegrant is
20: 1-5: 1, wherein it is preferred that 20: 1.
5. pharmaceutical composition according to claim 1, it is characterised in that the filler is Lactis Anhydrous, microcrystalline cellulose
One or more in element and calcium phosphate dibasic anhydrous.
6. pharmaceutical composition according to claim 1, it is characterised in that the lubricant is magnesium stearate.
7. pharmaceutical composition according to claim 1, it is characterised in that the crystal form of the Etoricoxib is crystal form V.
8. according to claim 1-7 any one of them pharmaceutical compositions, it is characterised in that the size distribution of the Etoricoxib
For：The preparation method of D90≤30 μm is：
S1：A part of filler and Etoricoxib is taken to grind 30-60min, the quality of the Etoricoxib and filler after mixing
Than for 3: 1-1: 1；
S2：Powder after grinding is input in airslide disintegrating mill by dry nitrogen, obtains the mixed-powder I of D90≤100 μm；Its
In, feed speed is 4.0-6.0kg/h, air pressure 1 × 105-5×105Pa；
S3：Take S2 mixed-powder and grinding after disintegrant be uniformly mixed, be input in airslide disintegrating mill, obtained by dry nitrogen
Obtain the mixed-powder II of D90≤30 μm；Wherein, feed speed is 1.0-3.0kg/h, air pressure 1 × 105-5×105Pa。
A kind of 9. tablet containing such as claim 1~8 any one of them pharmaceutical composition.
10. the preparation method of tablet as claimed in claim 9, it is characterised in that comprise the following steps：
1) just mix：Recipe quantity mixed-powder II, remaining filler are uniformly mixed, the lubricant grinding added in adding is mixed
Close, obtain mixtures III；
2) pelletize：Mixtures III is pelletized by dry granulating machine to obtain mixture IV；
3) it is total mixed：It is uniform that mixture IV adds additional mix lubricant；
4) tabletting：Φ 10mm scrobicula stampings, hardness range are controlled in 80-130N；
5) it is coated：Coating solution is prepared in the ratio of 12% (w/w), coating to weightening is 3%-5%.
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