CN107898787B - 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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- CN107898787B CN107898787B CN201711362158.3A CN201711362158A CN107898787B CN 107898787 B CN107898787 B CN 107898787B CN 201711362158 A CN201711362158 A CN 201711362158A CN 107898787 B CN107898787 B CN 107898787B
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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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- 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
- A61K9/28—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 fields, specifically, are related to a kind of pharmaceutical composition and its preparation and preparation method.Contain Etoricoxib in pharmaceutical composition of the invention, the size distribution of Etoricoxib is：D90≤30μm.The present invention controls the granularity of Etoricoxib in a specific range, to significantly improve the dissolution rate of pharmaceutical composition of the present invention.
Description
Technical field
The present invention relates to drug fields, specifically, are related to a kind of pharmaceutical composition and its preparation and preparation method.
Background technique
Etoricoxib (Etoricoxib) is a kind of highly selective Transitional cell carcinomas (COX-2) inhibitor, chemical name：[5-
Chloro- 2- (6- picoline -3- base) -3- (4- sulfonyloxy methyl phenyl) pyridine], structural formula is as follows：
Etoricoxib have it is anti-inflammatory, bring down a fever and analgesic effect, suitable for treating osteoarthritis acute stage and chronic phase
Sings and symptoms also can 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 have the patient of gastrointestinal tract risk using 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 drug after preparation is lower.Chinese patent
CN200580037915 discloses a kind of method of 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 drug
Contain 10% (weight) -40% (weight) Etoricoxib, 3% (weight) -25% (weight) disintegrating agent and its other medicine in composition
Acceptable excipient on.Disintegrating agent can be selected from starch, croscarmellose sodium, sodium carboxymethyl starch, the poly- dimension of crosslinking
One or more of ketone, low-substituted hydroxypropyl cellulose, povidone, microcrystalline cellulose.But it not can effectively 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 drug.
In order to improve bioavilability, generally requires and crushing operation is carried out to the API of drug, increase body absorption to reduce partial size.Powder
The tablet of last direct tablet compressing preparation is although easy to operate, but there are the risks of mixture homogeneity for raw material lesser for partial size.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 pharmaceutical composition and preparation method thereof containing Etoricoxib that the present invention provides a kind of, this method are examined using support
Specific disintegrating agent and solubilizer is added using dry granulation process for V in former times crystal form, effectively facilitates medicine disintegration dissolution, improves
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.
Summary of the invention
First invention purpose of the invention is to propose a kind of pharmaceutical composition.
Second goal of the invention of the invention is to propose the preparation containing the pharmaceutical composition.
Third goal of the invention of the invention is to propose the preparation method of said preparation.
In order to complete the purpose of the present invention, the technical solution used for：
First aspect present invention proposes a kind of pharmaceutical composition, containing Etoricoxib, disintegrating agent, filler, lubricant and
Other pharmaceutically acceptable auxiliary materials；Wherein, the size distribution of the Etoricoxib is：D90≤30μm.
Wherein, D90 refers to that the cumulative particle sizes distribution number of Etoricoxib 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, in the range the pharmaceutical composition of the Etoricoxib of granularity
Dissolution rate is significantly improved, so that the bioavilability of Etoricoxib can be improved.
Further, which includes 10% (weight) -30% (weight) Etoricoxib, 2% (weight) -6% (weight
Amount) disintegrating agent, 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, Etoricoxib accounts for 90% less than the particle between 30 μm, the particle less than 10 μm accounts for 50%, less than 5 μm
Grain accounts for 10%.The mixture homogeneity of medicament powder during the preparation process also can be improved in Etoricoxib of the embodiment of the present invention.
It include 10% (weight) -30% (weight) Etoricoxib, 2% (weight in the pharmaceutical composition of the embodiment of the present invention
Amount) -6% (weight) disintegrating agent, 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
Disintegrating agent dosage reduce.
Further, the disintegrating agent is croscarmellose sodium.Croscarmellose sodium is met water and is disintegrated rapidly,
As the disintegration rate for effectively facilitating main ingredient for disintegrating agent.Also, sodium atom and bulk pharmaceutical chemicals in croscarmellose sodium
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 increase the stability of tablet.
Further, the weight ratio of the Etoricoxib and disintegrating agent is 20: 1-5: 1, wherein it is preferred that 20: 1.
Further, the filler is one of Lactis Anhydrous, microcrystalline cellulose and calcium phosphate dibasic anhydrous or a variety of.
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：Grind 30-60min after taking a part of filler and Etoricoxib to mix, 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：It takes the mixed-powder of S2 and the disintegrating agent after grinding to be uniformly mixed, airslide disintegrating mill is input to by dry nitrogen
In, obtain the mixed-powder II of 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 within the scope of the specified particle size can be prepared by the method for micronization, be led to
Cross that the Etoricoxib form that is prepared of micronization is uniform, and surface is smooth, and be added in preparation process specific disintegrating agent and
Filler is added without plus solvent, avoids the phenomenon for meeting water or alcohol Etoricoxib turn crystalline substance and partial size becomes smaller what the uniformity was deteriorated
Problem is more conducive to improving the mixture homogeneity of medicament powder during the 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, includes the following steps：
1) it just mixes：Recipe quantity mixed-powder II, filler are uniformly mixed, the lubricant ground and mixed added in being added,
Obtain mixtures III；
2) it pelletizes：Mixtures III is pelletized to obtain mixture IV by dry granulating machine；
3) total mix：It is uniform that additional mix lubricant is added in mixture IV；
4) tabletting：Φ 10mm scrobicula stamping, hardness range are controlled in 80-130N；
5) it is coated：Coating solution is prepared in the ratio of 12% (w/w), coating to weight gain 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 sufficiently full
The requirement of sufficient embrittlement degree will not be crushed, sliver in storage and transportational process, and further ensure 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 the phenomenon of crystalline substance can be turned in the presence of chance water or alcohol by avoiding raw material in wet-granulation process
The problem of.
Optionally, preparation method further includes the steps that coating, it is preferred that the range 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 solution of the present invention attainable technical effect of institute at least that：
It uses Etoricoxib crystal form for V, using ultra micro dusting and dry granulation process, specific disintegrating agent and solubilising is added
Agent effectively facilitates medicine disintegration dissolution, improves bioavilability, while being added without plus solvent in preparation engineering, avoid chance
Water or alcohol Etoricoxib turn brilliant phenomenon and partial size and become smaller 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.
Specific embodiment
Present invention will be further explained below with reference to specific examples.It should be understood that these embodiments are merely to illustrate the present invention
Rather than it limits 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：
S1：60min is ground after taking filler 120g and Etoricoxib 120g to mix；
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：It takes the mixed-powder of S2 and the disintegrating agent 6g after grinding to 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 the homogeneous mixture of 200g Lactis Anhydrous and 70g microcrystalline cellulose；Disintegrating agent is crosslinking carboxylic first
Base sodium cellulosate；
Method for preparing tablet thereof：
1) it just mixes：Above-mentioned mixed-powder II and 150g filler are uniformly mixed, the lubricant 2.2g grinding added in being added
Mixing, obtains mixtures III；
2) it pelletizes：Mixtures III is pelletized to obtain mixture IV by dry granulating machine；
3) total mix：Mixture IV is added additional lubricant 2.2g and is uniformly mixed；
4) tabletting：Φ 10mm scrobicula stamping, hardness range are controlled in 100N；
5) it is coated：Coating solution is prepared in the ratio of 12% (w/w), coating to weight gain is 4%.
Wherein, filler is the homogeneous mixture of 200g Lactis Anhydrous and 70g microcrystalline cellulose；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：
S1：45min is ground after taking filler 60g and Etoricoxib 120g to mix；
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：It takes the mixed-powder of S2 and the disintegrating agent 15g after grinding to 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 the homogeneous mixture of 100g calcium phosphate dibasic anhydrous and 170g microcrystalline cellulose；Disintegrating agent is to hand over
Join sodium carboxymethylcellulose；
Method for preparing tablet thereof：
1) it just mixes：Above-mentioned mixed-powder II and 210g filler are uniformly mixed, the lubricant 2.4g grinding added in being added
Mixing, obtains mixtures III；
2) it pelletizes：Mixtures III is pelletized to obtain mixture IV by dry granulating machine；
3) total mix：Mixture IV is added additional lubricant 2.0g and is uniformly mixed；
4) tabletting：Φ 10mm scrobicula stamping, hardness range are controlled in 130N；
5) it is coated：Coating solution is prepared in the ratio of 12% (w/w), coating to weight gain is 5%.
Wherein, filler is the homogeneous mixture of 100g calcium phosphate dibasic anhydrous and 170g microcrystalline cellulose；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：
S1：30min is ground after taking filler 40g and Etoricoxib 120g to mix；
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：It takes the mixed-powder of S2 and the disintegrating agent 24g after grinding to 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 the homogeneous mixture of 200g Lactis Anhydrous and 70g microcrystalline cellulose；Disintegrating agent is crosslinking carboxylic first
Base sodium cellulosate；
Method for preparing tablet thereof：
1) it just mixes：Above-mentioned mixed-powder II and 230g filler are uniformly mixed, the lubricant 2.2g grinding added in being added
Mixing, obtains mixtures III；
2) it pelletizes：Mixtures III is pelletized to obtain mixture IV by dry granulating machine；
3) total mix：Mixture IV is added additional lubricant 2.2g and is uniformly mixed；
4) tabletting：Φ 10mm scrobicula stamping, hardness range are controlled in 80N；
5) it is coated：Coating solution is prepared in the ratio of 12% (w/w), coating to weight gain is 3%.
Wherein, filler is the homogeneous mixture of 200g Lactis Anhydrous and 70g microcrystalline cellulose；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：
S1：40min is ground after taking filler 60g and Etoricoxib 120g to mix；
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：It takes the mixed-powder of S2 and the disintegrating agent 6g after grinding to 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 the homogeneous mixture of 100g calcium phosphate dibasic anhydrous and 170g microcrystalline cellulose；Disintegrating agent is to hand over
Join sodium carboxymethylcellulose；
Method for preparing tablet thereof：
1) it just mixes：Above-mentioned mixed-powder II and 210g filler are uniformly mixed, the lubricant 2.4g grinding added in being added
Mixing, obtains mixtures III；
2) it pelletizes：Mixtures III is pelletized to obtain mixture IV by dry granulating machine；
3) total mix：Mixture IV is added additional lubricant 2.0g and is uniformly mixed；
4) tabletting：Φ 10mm scrobicula stamping, hardness range are controlled in 130N；
5) it is coated：Coating solution is prepared in the ratio of 12% (w/w), coating to weight gain is 5%.
Wherein, filler is the homogeneous mixture of 100g calcium phosphate dibasic anhydrous and 170g microcrystalline cellulose；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：
S1：45min is ground after taking filler 80g and Etoricoxib 120g to mix；
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：It takes the mixed-powder of S2 and the disintegrating agent 6g after grinding to 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 the homogeneous mixture of 200g calcium phosphate dibasic anhydrous and 70g microcrystalline cellulose；Disintegrating agent is crosslinking
Sodium carboxymethylcellulose；
Method for preparing tablet thereof：
1) it just mixes：Above-mentioned mixed-powder II and 190g filler are uniformly mixed, the lubricant 2.2g grinding added in being added
Mixing, obtains mixtures III；
2) it pelletizes：Mixtures III is pelletized to obtain mixture IV by dry granulating machine；
3) total mix：Mixture IV is added additional lubricant 2.2g and is uniformly mixed；
4) tabletting：Φ 10mm scrobicula stamping, hardness range are controlled in 120N；
5) it is coated：Coating solution is prepared in the ratio of 12% (w/w), coating to weight gain is 4%.
Wherein, filler is the homogeneous mixture of 200g calcium phosphate dibasic anhydrous and 70g microcrystalline cellulose；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：
S1：45min is ground after taking filler 100g and Etoricoxib 120g to mix；
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：It takes the mixed-powder of S2 and the disintegrating agent 6g after grinding to 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 anhydrous, 50g Lactis Anhydrous and 170g microcrystalline cellulose；
Disintegrating agent is croscarmellose sodium；
Method for preparing tablet thereof：
1) it just mixes：Above-mentioned mixed-powder II and 170g filler are uniformly mixed, the lubricant 2.4g grinding added in being added
Mixing, obtains mixtures III；
2) it pelletizes：Mixtures III is pelletized to obtain mixture IV by dry granulating machine；
3) total mix：Mixture IV is added additional lubricant 2.0g and is uniformly mixed；
4) tabletting：Φ 10mm scrobicula stamping, hardness range are controlled in 100N；
5) it is coated：Coating solution is prepared in the ratio of 12% (w/w), coating to weight gain is 4%.
Wherein, filler is the homogeneous mixture of 50g calcium phosphate dibasic anhydrous, 50g Lactis Anhydrous and 170g microcrystalline cellulose；
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) it weighs：The croscarmellose sodium and 70g that add in 120g Etoricoxib, 200g Lactis Anhydrous, 6g is micro-
Crystalline cellulose mixing adds the interior 2.2g magnesium stearate mixing added, obtains mixture I；
(2) it pelletizes：Mixture I is pelletized with dry granulating machine, obtains Etoricoxib medicament composition granule；
(3) total mix：Etoricoxib medicament composition granule is added magnesium stearate 2.2g and is uniformly mixed；
(4) tabletting：Φ 10mm scrobicula stamping, hardness range control 100N；
(5) it is coated：Coating solution is prepared in the ratio of 12% (w/w), coating to weight gain 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) it weighs：The croscarmellose sodium and 70g that add in 120g Etoricoxib, 200g Lactis Anhydrous, 6g is micro-
Crystalline cellulose mixing adds the interior 2.2g magnesium stearate mixing added, obtains mixture I；
(2) it pelletizes：Mixture I is pelletized with dry granulating machine, obtains Etoricoxib medicament composition granule；
(3) total mix：Etoricoxib medicament composition granule is added magnesium stearate 2.2g and is uniformly mixed；
(4) tabletting：Φ 10mm scrobicula stamping, hardness range control 100N；
(5) it is coated：Coating solution is prepared in the ratio of 12% (w/w), coating to weight gain 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：
S1：60min is ground after taking filler 120g and Etoricoxib 120g to mix；
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：It takes the mixed-powder of S2 and the disintegrating agent 6g after grinding to 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 the homogeneous mixture of 200g Lactis Anhydrous and 70g microcrystalline cellulose；Disintegrating agent is crosslinking carboxylic first
Base sodium cellulosate；
Method for preparing tablet thereof：
1) it just mixes：Above-mentioned mixed-powder II and 150g filler are uniformly mixed, the lubricant 2.2g grinding added in being added
Mixing, obtains mixtures III；
2) it pelletizes：Mixtures III is pelletized to obtain mixture IV by dry granulating machine；
3) total mix：Mixture IV is added additional lubricant 2.2g and is uniformly mixed；
4) tabletting：Φ 10mm scrobicula stamping, hardness range are controlled in 100N；
5) it is coated：Coating solution is prepared in the ratio of 12% (w/w), coating to weight gain is 4%.
Wherein, filler is the homogeneous mixture of 200g Lactis Anhydrous and 70g microcrystalline cellulose；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：
S1：60min is ground after taking filler 120g and Etoricoxib 120g to mix；
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：It takes the mixed-powder of S2 and the disintegrating agent 6g after grinding to 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 the homogeneous mixture of 200g Lactis Anhydrous and 70g microcrystalline cellulose；Disintegrating agent is dried starch；
Method for preparing tablet thereof：
1) it just mixes：Above-mentioned mixed-powder II and 150g filler are uniformly mixed, the lubricant 2.2g grinding added in being added
Mixing, obtains mixtures III；
2) it pelletizes：Mixtures III is pelletized to obtain mixture IV by dry granulating machine；
3) total mix：Mixture IV is added additional lubricant 2.2g and is uniformly mixed；
4) tabletting：Φ 10mm scrobicula stamping, hardness range are controlled in 100N；
5) it is coated：Coating solution is prepared in the ratio of 12% (w/w), coating to weight gain is 4%.
Wherein, filler is the homogeneous mixture of 200g Lactis Anhydrous and 70g microcrystalline cellulose；Lubricant is stearic acid
Magnesium；Coating solution is the Opadry II solution that mass percent concentration is 12%.
Embodiment 7
According to the second method of dissolution rate in pharmacopeia in 2015 to embodiment and comparative example prepared by tablet be measured.
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 not to be defined to Etoricoxib partial size, manufactured tablet；Comparative example 2 is individually to Etoricoxib
Granularity is handled, manufactured tablet；Comparative example 3 is to change lubricant, and other conditions are constant, manufactured tablet；Comparative example 4 is
Change disintegrating agent, manufactured tablet；
By the Dissolution experiments of table 11 it is found that the Etoricoxib for the granularity for using the specific preparation method of the present invention to obtain is equal
It is remarkably improved the dissolution rate of tablet, the dissolution rate without being defined to Etoricoxib granularity is obviously very low；Individually to support
It examines former times granularity to be defined and be added without filler and disintegrating agent, dissolution rate decrease to some degree；Change disintegrating agent and profit
Lubrication prescription has biggish negatively influencing to solubility.
Embodiment 8
Uniformity of dosage units and assay are carried out to 10 batches of samples according to official method.
Every mark content (X)：
Averagely indicate content
The absolute value of the difference (A) of labelled amount and mean value：
Standard deviation (S)：
Criterion：1. then the uniformity of dosage units of test sample meets regulation such as A+1.80S≤15.0.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 30 mean value X, the absolute value of the difference A of standard deviation S and labelled amount；Such as A+
1.45S≤15.0, then the uniformity of dosage units of test sample meets regulation；If A=1.45 > 15.0, against regulation.
The uniformity of dosage units that above-mentioned tablet is measured according to States Pharmacopoeia specifications, obtained experimental result are as shown in table 12：
Table 12
Comparative example 1 is not to be defined to Etoricoxib partial size, manufactured tablet；Comparative example 2 is individually to Etoricoxib
Granularity is handled, manufactured tablet；Comparative example 3 is to change lubricant, and other conditions are constant, manufactured tablet；Comparative example 4 is
Change disintegrating agent, manufactured tablet；
It is tested by the uniformity of dosage units of table 12 it is found that 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
Rationally, preparation process design is rationally, indispensable for component collocation, and the tablet that this specific combination is constituted produces apparent
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 several possible variations and modification, therefore this hair
Bright protection scope should be quasi- with range that the claims in the present invention are defined.
Claims (6)
1. a kind of pharmaceutical composition, which is characterized in that the pharmaceutical composition includes that 120g Etoricoxib, 270g filler, 6g collapse
Solve agent, 4.4g lubricant；
Wherein, the size distribution of the Etoricoxib is：D90≤30 μm, D50≤10 μm, D10≤5 μm；
The disintegrating agent is croscarmellose sodium；
The size distribution of the Etoricoxib is that the preparation method of D90≤30 μm is：
S1：30-60min, the quality of the Etoricoxib and filler are ground after taking a part of filler and Etoricoxib to mix
Than being 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：It takes the mixed-powder of S2 and the disintegrating agent after grinding to be uniformly mixed, is input in airslide disintegrating mill, is 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。
2. pharmaceutical composition according to claim 1, which is characterized in that the filler is Lactis Anhydrous, microcrystalline cellulose
One of element and calcium phosphate dibasic anhydrous are a variety of.
3. pharmaceutical composition according to claim 1, which is characterized in that the lubricant is magnesium stearate.
4. pharmaceutical composition according to claim 1, which is characterized in that the crystal form of the Etoricoxib is crystal form V.
5. a kind of tablet containing pharmaceutical composition as claimed in claim 4.
6. the preparation method of tablet as claimed in claim 5, which is characterized in that include the following steps：
1) it just mixes：Recipe quantity mixed-powder II, remaining filler are uniformly mixed, the lubricant grinding added in being added is mixed
It closes, obtains mixtures III；
2) it pelletizes：Mixtures III is pelletized to obtain mixture IV by dry granulating machine；
3) total mix：It is uniform that additional mix lubricant is added in mixture IV；
4) tabletting：Φ 10mm scrobicula stamping, hardness range are controlled in 80-130N；
5) it is coated：Coating solution is prepared in the ratio of 12% (w/w), coating to weight gain is 3%-5%.
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