CN106727378A - A kind of tablet composition containing ticagrelor main ingredient and preparation method thereof - Google Patents
A kind of tablet composition containing ticagrelor main ingredient and preparation method thereof Download PDFInfo
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- CN106727378A CN106727378A CN201611236309.6A CN201611236309A CN106727378A CN 106727378 A CN106727378 A CN 106727378A CN 201611236309 A CN201611236309 A CN 201611236309A CN 106727378 A CN106727378 A CN 106727378A
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- China
- Prior art keywords
- ticagrelor
- mass ratio
- mesh
- mannitol
- monohydrogen phosphate
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- OEKWJQXRCDYSHL-FNOIDJSQSA-N ticagrelor Chemical compound C1([C@@H]2C[C@H]2NC=2N=C(N=C3N([C@H]4[C@@H]([C@H](O)[C@@H](OCCO)C4)O)N=NC3=2)SCCC)=CC=C(F)C(F)=C1 OEKWJQXRCDYSHL-FNOIDJSQSA-N 0.000 title claims abstract description 72
- 229960002528 ticagrelor Drugs 0.000 title claims abstract description 72
- 238000002360 preparation method Methods 0.000 title claims abstract description 24
- 239000002075 main ingredient Substances 0.000 title claims abstract description 15
- 239000007916 tablet composition Substances 0.000 title claims abstract description 13
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims abstract description 24
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims abstract description 22
- 229930195725 Mannitol Natural products 0.000 claims abstract description 22
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 claims abstract description 22
- 239000011248 coating agent Substances 0.000 claims abstract description 22
- 238000000576 coating method Methods 0.000 claims abstract description 22
- 235000019700 dicalcium phosphate Nutrition 0.000 claims abstract description 22
- 239000000594 mannitol Substances 0.000 claims abstract description 22
- 235000010355 mannitol Nutrition 0.000 claims abstract description 22
- 238000006467 substitution reaction Methods 0.000 claims abstract description 21
- 229920000881 Modified starch Polymers 0.000 claims abstract description 20
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims abstract description 18
- 239000001863 hydroxypropyl cellulose Substances 0.000 claims abstract description 18
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims abstract description 18
- 239000011734 sodium Substances 0.000 claims abstract description 17
- 229910052708 sodium Inorganic materials 0.000 claims abstract description 17
- 229920002472 Starch Polymers 0.000 claims abstract description 15
- 235000019698 starch Nutrition 0.000 claims abstract description 15
- 239000008107 starch Substances 0.000 claims abstract description 15
- 235000019359 magnesium stearate Nutrition 0.000 claims abstract description 12
- 239000011122 softwood Substances 0.000 claims description 14
- 239000000463 material Substances 0.000 claims description 13
- 229940032147 starch Drugs 0.000 claims description 13
- 239000000853 adhesive Substances 0.000 claims description 10
- 230000001070 adhesive effect Effects 0.000 claims description 10
- UHZZMRAGKVHANO-UHFFFAOYSA-M chlormequat chloride Chemical compound [Cl-].C[N+](C)(C)CCCl UHZZMRAGKVHANO-UHFFFAOYSA-M 0.000 claims description 7
- 239000007888 film coating Substances 0.000 claims description 7
- 238000009501 film coating Methods 0.000 claims description 7
- 239000012530 fluid Substances 0.000 claims description 7
- 239000003595 mist Substances 0.000 claims description 7
- 210000002784 stomach Anatomy 0.000 claims description 7
- 230000004584 weight gain Effects 0.000 claims description 7
- 235000019786 weight gain Nutrition 0.000 claims description 7
- 235000020985 whole grains Nutrition 0.000 claims description 7
- 239000000203 mixture Substances 0.000 claims description 6
- 235000015424 sodium Nutrition 0.000 claims description 6
- 239000003795 chemical substances by application Substances 0.000 claims description 4
- 239000000835 fiber Substances 0.000 claims description 4
- 238000005469 granulation Methods 0.000 claims description 4
- 230000003179 granulation Effects 0.000 claims description 4
- -1 hydroxypropyl Chemical group 0.000 claims description 4
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 3
- 235000014113 dietary fatty acids Nutrition 0.000 claims description 3
- 239000000194 fatty acid Substances 0.000 claims description 3
- 229930195729 fatty acid Natural products 0.000 claims description 3
- 150000004665 fatty acids Chemical class 0.000 claims description 3
- 239000011777 magnesium Substances 0.000 claims description 3
- 229910052749 magnesium Inorganic materials 0.000 claims description 3
- 229940080313 sodium starch Drugs 0.000 claims description 3
- 238000004090 dissolution Methods 0.000 abstract description 21
- 238000000034 method Methods 0.000 abstract description 5
- 238000001035 drying Methods 0.000 abstract description 2
- 238000004519 manufacturing process Methods 0.000 abstract description 2
- 238000005550 wet granulation Methods 0.000 abstract description 2
- 239000003814 drug Substances 0.000 description 6
- 230000000694 effects Effects 0.000 description 5
- 238000000338 in vitro Methods 0.000 description 4
- 235000013339 cereals Nutrition 0.000 description 3
- 239000007884 disintegrant Substances 0.000 description 3
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 3
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 3
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 3
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- AQLLBJAXUCIJSR-UHFFFAOYSA-N OC(=O)C[Na] Chemical compound OC(=O)C[Na] AQLLBJAXUCIJSR-UHFFFAOYSA-N 0.000 description 2
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 2
- 238000004132 cross linking Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000013049 sediment Substances 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 206010067484 Adverse reaction Diseases 0.000 description 1
- 206010011224 Cough Diseases 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000001133 acceleration Effects 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 229920003020 cross-linked polyethylene Polymers 0.000 description 1
- 239000004703 cross-linked polyethylene Substances 0.000 description 1
- 239000012738 dissolution medium Substances 0.000 description 1
- 238000009506 drug dissolution testing Methods 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000005286 illumination Methods 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 1
- 239000002951 street drug Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- 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
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
-
- A—HUMAN NECESSITIES
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- 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
-
- 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
-
- 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
-
- 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
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- 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
- A61K9/2806—Coating materials
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Inorganic Chemistry (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention discloses a kind of tablet composition containing ticagrelor main ingredient and preparation method thereof, the described tablet composition containing ticagrelor main ingredient includes ticagrelor, mannitol, calcium monohydrogen phosphate, pregelatinized starch, substitution hydroxypropylcellulose high, sodium carboxymethyl starch and magnesium stearate, and ticagrelor, the mass ratio of mannitol are 1：0.5 3, ticagrelor, the mass ratio of calcium monohydrogen phosphate are 1：0.5 3, ticagrelor, the mass ratio of pregelatinized starch are 1：03, ticagrelor, the mass ratio of substitution hydroxypropylcellulose high are 30 80：1, ticagrelor, the mass ratio of sodium carboxymethyl starch are 5 15：1, ticagrelor, the mass ratio of magnesium stearate are 10 50：1.The present invention uses wet granulation, fluidized bed drying, compressing tablet, the technique productions of coating, and the ticagrelor piece dissolution rate of preparation is fast, and stable performance, preparation method technical process is simple, it is easy to operates and realizes, is suitable to industrial application.
Description
Technical field
The invention belongs to field of medicine preparation, and in particular to a kind of tablet composition containing ticagrelor main ingredient and its system
Preparation Method.
Background technology
Ticagrelor is low aqueous solubility material, and under the conditions of 20 ± 5 DEG C, the medicine solubility is 0.016mg/ml, therefore
, it is necessary to screen suitable auxiliary material and preparation process in the development process of ticagrelor tablet, make ticagrelor piece have compared with
Good dissolution rate, dissolution is fully absorbed after enabling ticagrelor oral, and embodies good bioavilability and curative effect of medication.
But current commercially available ticagrelor Dissolution of Tablet is relatively low, and dissolution inequality, so as to influence fully absorbing for medicine, influences it
Bioavilability and curative effect, therefore, the present invention needs to solve following two problems：
1st, stability grinds consistent with original：The relevant material of 0 day sample of sample prepared according to this patent is less than former triturate and produces
Product, quality is more excellent；Long-term 24 months and acceleration June condition stability inferior and former triturate uniform quality.
2nd, dissolution in vitro fitting：To ensure that clinical efficacy grinds consistent with original, In Vitro Dissolution fitting is used as evaluation similarity
Important indicator；Contrast own product is with listing product 4 kinds in 0.1mol/L hydrochloric acid, pH4.5 acetate, pH6.8 phosphate and water
Stripping curve similarity in the dissolution medium of different pH value, as a result shows the dissolution similarity in 4 kinds of media more than 65.
Patent CN105193759A dissolutions Testing index only investigates final dissolution rate, has not contrasted each under various ambient conditions
The dissolution data of sample point.The release absorption of medicine in human body etc. is simulated conventionally by In Vitro Dissolution, then is examined by BE
Whether consistent examine vivo biodistribution availability；Patent CN104523640A dissolutions Testing index investigates four stripping curves, but dissolution
Curve is above original and grinds commercially available product, feeds back to internal i.e. dissolution too fast, it may occur however that dosage comes down in torrents, and produces adverse reaction；This is specially
Sharp dissolution Testing index investigates four stripping curves, and it is almost consistent that stripping curve grinds commercially available product with original.
The content of the invention
Goal of the invention：The present invention provides a kind of tablet composition containing ticagrelor main ingredient and preparation method thereof.
Technical scheme：A kind of tablet composition containing ticagrelor main ingredient, the described piece containing ticagrelor main ingredient
Agent composition includes ticagrelor, mannitol, calcium monohydrogen phosphate, pregelatinized starch, substitution hydroxypropylcellulose high, sodium carboxymethyl starch
And magnesium stearate, the ticagrelor, the mass ratio of mannitol are 1：0.5-3, the ticagrelor, the mass ratio of calcium monohydrogen phosphate
It is 1：0.5-3, the ticagrelor, the mass ratio of pregelatinized starch are 1：0-3, the ticagrelor, substitution hydroxypropyl fiber high
The mass ratio of element is 30-80：1, the ticagrelor, the mass ratio of sodium carboxymethyl starch are 5-15：1, it is the ticagrelor, hard
The mass ratio of fatty acid magnesium is 10-50：1.
A kind of preparation method of the tablet composition containing ticagrelor main ingredient described in basis, comprises the following steps：
(1) sieve：By ticagrelor micro mist to 200 mesh, mannitol is crossed into 60 mesh, by pregelatinized starch, calcium monohydrogen phosphate and
Sodium carboxymethyl starch crosses 80 mesh sieves；
(2) solution is prepared：The solution for standby of 3% substitution hydroxypropylcellulose high is prepared, the coating solution for preparing 5% is standby；
(3) mix：Ticagrelor, mannitol, pregelatinized starch, calcium monohydrogen phosphate, carboxymethyl is weighed respectively by recipe quantity to form sediment
Powder sodium sieve is well mixed, and it is adhesive softwood to use 3% substitution hydroxypropylcellulose solution high, and made softwood is crossed into 24 mesh systems
Grain；
(4) dry：The wet granular that will be made is dried with fluid bed, and control EAT is in 75~80 DEG C, material temperature
40~50 DEG C of degree, within dry materials moisture to 3.0%；Dry particl is crossed into 18 mesh whole grains, adds recipe quantity magnesium stearate to mix
Close uniform, using 9mm circular die compressing tablets；
(5) it is coated：It is coated using stomach dissolved film coating pre-mix dose, coating weight gain 2%~4%, adjusting parameter is entered
Row is coated.Coating parameter：Engine speed：25~30rpm；Piece bed tempertaure：35~45 DEG C；Hydrojet speed：1.0~1.5rpm.
Beneficial effect：The ticagrelor tablet composition that the present invention is provided uses wet granulation, fluidized bed drying, compressing tablet, bag
The technique productions of clothing, the ticagrelor piece dissolution rate of preparation is fast, stable performance.Preparation method technical process of the present invention is simple,
Easily operated realization, is suitable to industrial application.Each auxiliary material mutually acts synergistically with bulk drug in the amount ranges for limiting,
Make the dissolution rate of the ticagrelor piece of preparation higher than existing marketed tablet, and show and street drug identical dissolution row
For, it is ensured that ticagrelor piece has preferable assimilation effect, and improves the bioavilability of ticagrelor piece.The present invention is replaced
Ge Ruiluo piece impurity contents are few, the stable performance under high temperature, illumination condition.
Specific embodiment
With reference to specific embodiment, the present invention will be described in detail.
It is summarized as follows：A kind of tablet composition containing ticagrelor main ingredient, the described piece containing ticagrelor main ingredient
Agent composition includes ticagrelor, mannitol, calcium monohydrogen phosphate, pregelatinized starch, substitution hydroxypropylcellulose high, sodium carboxymethyl starch
And magnesium stearate, the ticagrelor, the mass ratio of mannitol are 1：0.5-3, the ticagrelor, the mass ratio of calcium monohydrogen phosphate
It is 1：0.5-3, the ticagrelor, the mass ratio of pregelatinized starch are 1：0-3, the ticagrelor, substitution hydroxypropyl fiber high
The mass ratio of element is 30-80：1, the ticagrelor, the mass ratio of sodium carboxymethyl starch are 5-15：1, it is the ticagrelor, hard
The mass ratio of fatty acid magnesium is 10-50：1.
A kind of preparation method of the tablet composition containing ticagrelor main ingredient described in basis, comprises the following steps：
(1) sieve：By ticagrelor micro mist to 200 mesh, mannitol is crossed into 60 mesh, by pregelatinized starch, calcium monohydrogen phosphate and
Sodium carboxymethyl starch crosses 80 mesh sieves；
(2) solution is prepared：The solution for standby of 3% substitution hydroxypropylcellulose high is prepared, the coating solution for preparing 5% is standby；
(3) mix：Ticagrelor, mannitol, pregelatinized starch, calcium monohydrogen phosphate, carboxymethyl is weighed respectively by recipe quantity to form sediment
Powder sodium sieve is well mixed, and it is adhesive softwood to use 3% substitution hydroxypropylcellulose solution high, and made softwood is crossed into 24 mesh systems
Grain；
(4) dry：The wet granular that will be made is dried with fluid bed, and control EAT is in 75~80 DEG C, material temperature
40~50 DEG C of degree, within dry materials moisture to 3.0%；Dry particl is crossed into 18 mesh whole grains, adds recipe quantity magnesium stearate to mix
Close uniform, using 9mm circular die compressing tablets；
(5) it is coated：It is coated using stomach dissolved film coating pre-mix dose, coating weight gain 2%~4%, adjusting parameter is entered
Row is coated.Coating parameter：Engine speed：25~30rpm；Piece bed tempertaure：35~45 DEG C；Hydrojet speed：1.0~1.5rpm.
Specific implementation case 1：Excipient ratios are not in the range of
The preparation prescription (in terms of 1000) of ticagrelor piece：
Preparation process：
(1) by ticagrelor micro mist to 200 mesh, mannitol is crossed into 60 mesh, calcium monohydrogen phosphate and sodium carboxymethyl starch is crossed 80
Mesh sieve.
(2) solution for standby of 3% substitution hydroxypropylcellulose high is prepared.The coating solution for preparing 5% is standby.
(3) ticagrelor, mannitol, calcium monohydrogen phosphate, sodium carboxymethyl starch sieve are weighed respectively by recipe quantity well mixed, is adopted
It is adhesive softwood with 3% substitution hydroxypropylcellulose solution high, made softwood is crossed into the granulation of 24 mesh.
(4) wet granular that will be made is dried with fluid bed, control EAT at 75~80 DEG C, temperature of charge 40~
50 DEG C, within dry materials moisture to 3.0%.Dry particl is crossed into 18 mesh whole grains, adds recipe quantity magnesium stearate to be well mixed,
Using 9mm circular die compressing tablets.
(5) it is coated using stomach dissolved film coating pre-mix dose, coating weight gain 2%~4%, adjusting parameter is wrapped
Clothing.Coating parameter：Engine speed：25~30rpm；Piece bed tempertaure：35~45 DEG C；Hydrojet speed：1.0~1.5rpm.
Specific implementation case 2：Cross linked polyvinyl pyrrolidone is selected in disintegration
The preparation prescription (in terms of 1000) of ticagrelor piece：
Preparation process：
(1) by ticagrelor micro mist to 200 mesh, mannitol is crossed into 60 mesh, pregelatinized starch, calcium monohydrogen phosphate and crosslinking is poly-
Ethylene ratio pyrrolidone crosses 80 mesh sieves.
(2) solution for standby of 3% substitution hydroxypropylcellulose high is prepared.The coating solution for preparing 5% is standby.
(3) ticagrelor, mannitol, pregelatinized starch, calcium monohydrogen phosphate, crosslinked polyethylene ratio is weighed respectively by recipe quantity to cough up
Alkanone sieve is well mixed, and it is adhesive softwood to use 3% substitution hydroxypropylcellulose solution high, and made softwood is crossed into 24 mesh systems
Grain.
(4) wet granular that will be made is dried with fluid bed, control EAT at 75~80 DEG C, temperature of charge 40~
50 DEG C, within dry materials moisture to 3.0%.Dry particl is crossed into 18 mesh whole grains, adds recipe quantity magnesium stearate to be well mixed,
Using 9mm circular die compressing tablets.
(5) it is coated using stomach dissolved film coating pre-mix dose, coating weight gain 2%~4%, adjusting parameter is wrapped
Clothing.Coating parameter：Engine speed：25~30rpm；Piece bed tempertaure：35~45 DEG C；Hydrojet speed：1.0~1.5rpm.
Specific implementation case 3：Adhesive selects Hydroxypropyl methylcellulose
The preparation prescription (in terms of 1000) of ticagrelor piece：
Preparation process：
(1) by ticagrelor micro mist to 200 mesh, mannitol is crossed into 60 mesh, by pregelatinized starch, calcium monohydrogen phosphate and carboxymethyl
Sodium starch crosses 80 mesh sieves.
(2) solution for standby of 3% Hydroxypropyl methylcellulose is prepared.The coating solution for preparing 5% is standby.
(3) ticagrelor, mannitol, pregelatinized starch, calcium monohydrogen phosphate, sodium carboxymethyl starch sieve are weighed respectively by recipe quantity
Well mixed, it is adhesive softwood to use 3% Hydroxypropyl methylcellulose solution, and made softwood is crossed into the granulation of 24 mesh.
(4) wet granular that will be made is dried with fluid bed, control EAT at 75~80 DEG C, temperature of charge 40~
50 DEG C, within dry materials moisture to 3.0%.Dry particl is crossed into 18 mesh whole grains, adds recipe quantity magnesium stearate to be well mixed,
Using 9mm circular die compressing tablets.
(5) it is coated using stomach dissolved film coating pre-mix dose, coating weight gain 2%~4%, adjusting parameter is wrapped
Clothing.Coating parameter：Engine speed：25~30rpm；Piece bed tempertaure：35~45 DEG C；Hydrojet speed：1.0~1.5rpm.
Specific implementation case 4：Most preferably
The preparation prescription (in terms of 1000) of ticagrelor piece：
Preparation process：
(1) by ticagrelor micro mist to 200 mesh, mannitol is crossed into 60 mesh, by pregelatinized starch, calcium monohydrogen phosphate and carboxymethyl
Sodium starch crosses 80 mesh sieves.
(2) solution for standby of 3% substitution hydroxypropylcellulose high is prepared.The coating solution for preparing 5% is standby.
(3) ticagrelor, mannitol, pregelatinized starch, calcium monohydrogen phosphate, sodium carboxymethyl starch sieve are weighed respectively by recipe quantity
Well mixed, it is adhesive softwood to use 3% substitution hydroxypropylcellulose solution high, and made softwood is crossed into the granulation of 24 mesh.
(4) wet granular that will be made is dried with fluid bed, control EAT at 75~80 DEG C, temperature of charge 40~
50 DEG C, within dry materials moisture to 3.0%.Dry particl is crossed into 18 mesh whole grains, adds recipe quantity magnesium stearate to be well mixed,
Using 9mm circular die compressing tablets.
(5) it is coated using stomach dissolved film coating pre-mix dose, coating weight gain 2%~4%, adjusting parameter is wrapped
Clothing.Coating parameter：Engine speed：25~30rpm；Piece bed tempertaure：35~45 DEG C；Hydrojet speed：1.0~1.5rpm.
Specific implementation case 1
Specific implementation case 2
Specific implementation case 3
Specific implementation case 4
Conclusion：
1st, excipient selection is improper in specific implementation case 1 causes product stability poor；Dissolution is dissimilar.
2nd, the specific implementation selective cross-linking PVP of case 2 is led as disintegrant from same preparation technology
Disintegrant performance failure is caused, disintegration ability declines to a great extent, and In Vitro Dissolution is slack-off, correspond to and be characterized as curative effect in vivo less than former development
Agent.
3rd, adhesive selects hydroxypropyl cellulose in specific implementation case 3, and adhesive viscosity is higher than substitution hydroxypropyl fiber high
Element, dry particl hardness is higher, causes dissolution slower, corresponds to and is characterized as curative effect in vivo far below former triturate.
4th, only selected to rational categories of excipients and consumption, suitable disintegrant consumption ability in specific implementation case 4
Prepare product suitable and therapeutic equivalence with former triturate quality.
The present invention is not limited to above-mentioned preferred forms, and anyone can show that other are various under enlightenment of the invention
The product of form, however, make any change in its shape or structure, it is every with skill identical or similar to the present application
Art scheme, is within the scope of the present invention.
Claims (2)
1. a kind of tablet composition containing ticagrelor main ingredient, it is characterised in that：The described piece containing ticagrelor main ingredient
Agent composition includes ticagrelor, mannitol, calcium monohydrogen phosphate, pregelatinized starch, substitution hydroxypropylcellulose high, sodium carboxymethyl starch
And magnesium stearate, the ticagrelor, the mass ratio of mannitol are 1：0.5-3, the ticagrelor, the mass ratio of calcium monohydrogen phosphate
It is 1：0.5-3, the ticagrelor, the mass ratio of pregelatinized starch are 1：0-3, the ticagrelor, substitution hydroxypropyl fiber high
The mass ratio of element is 30-80：1, the ticagrelor, the mass ratio of sodium carboxymethyl starch are 5-15：1, it is the ticagrelor, hard
The mass ratio of fatty acid magnesium is 10-50：1.
2. a kind of preparation method of the tablet composition containing ticagrelor main ingredient according to claim 1, its feature exists
In：Comprise the following steps：
(1) sieve：By ticagrelor micro mist to 200 mesh, mannitol is crossed into 60 mesh, by pregelatinized starch, calcium monohydrogen phosphate and carboxylic first
Base sodium starch crosses 80 mesh sieves；
(2) solution is prepared：The solution for standby of 3% substitution hydroxypropylcellulose high is prepared, the coating solution for preparing 5% is standby；
(3) mix：Weigh ticagrelor, mannitol, pregelatinized starch, calcium monohydrogen phosphate, sodium carboxymethyl starch respectively by recipe quantity
Sieve is well mixed, and it is adhesive softwood to use 3% substitution hydroxypropylcellulose solution high, and made softwood is crossed into the granulation of 24 mesh；
(4) dry：The wet granular that will be made is dried with fluid bed, and control EAT is in 75~80 DEG C, temperature of charge 40
~50 DEG C, within dry materials moisture to 3.0%；Dry particl is crossed into 18 mesh whole grains, adds the mixing of recipe quantity magnesium stearate equal
It is even, using 9mm circular die compressing tablets；
(5) it is coated：It is coated using stomach dissolved film coating pre-mix dose, coating weight gain 2%~4%, adjusting parameter is wrapped
Clothing.Coating parameter：Engine speed：25~30rpm；Piece bed tempertaure：35~45 DEG C；Hydrojet speed：1.0~1.5rpm.
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| CN201611236309.6A CN106727378A (en) | 2016-12-28 | 2016-12-28 | A kind of tablet composition containing ticagrelor main ingredient and preparation method thereof |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2019170244A1 (en) * | 2018-03-08 | 2019-09-12 | Pharmaceutical Oriented Services Ltd. | Ticagrelor—containing tablet formulation |
| CN110327305A (en) * | 2019-06-26 | 2019-10-15 | 慧生医学科技(徐州)有限公司 | A kind of ticagrelor piece and preparation method thereof |
| CN111450072A (en) * | 2020-05-07 | 2020-07-28 | 江苏艾立康药业股份有限公司 | Ticagrelor controlled release tablet and preparation method thereof |
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|---|---|---|---|---|
| WO2011076749A2 (en) * | 2009-12-23 | 2011-06-30 | Ratiopharm Gmbh | Solid pharmaceutical dosage form |
| CN104650091A (en) * | 2014-01-24 | 2015-05-27 | 福州乾正药业有限公司 | Micronization and crystal form of ticagrelor and preparation method and pharmaceutical application of crystal form of ticagrelor |
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2016
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011076749A2 (en) * | 2009-12-23 | 2011-06-30 | Ratiopharm Gmbh | Solid pharmaceutical dosage form |
| CN104650091A (en) * | 2014-01-24 | 2015-05-27 | 福州乾正药业有限公司 | Micronization and crystal form of ticagrelor and preparation method and pharmaceutical application of crystal form of ticagrelor |
Non-Patent Citations (1)
| Title |
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| MD. SHAFAYAT HOSSAIN ET AL: "Formulation Development and Evaluation of Ticagrelor Tablet for Regulatory Market", 《JOURNAL OF APPLIED PHARMACEUTICAL SCIENCE》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2019170244A1 (en) * | 2018-03-08 | 2019-09-12 | Pharmaceutical Oriented Services Ltd. | Ticagrelor—containing tablet formulation |
| CN110327305A (en) * | 2019-06-26 | 2019-10-15 | 慧生医学科技(徐州)有限公司 | A kind of ticagrelor piece and preparation method thereof |
| CN111450072A (en) * | 2020-05-07 | 2020-07-28 | 江苏艾立康药业股份有限公司 | Ticagrelor controlled release tablet and preparation method thereof |
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Application publication date: 20170531 |