CN108969494A - A kind of Parecoxib Sodium durative action preparation and preparation method thereof - Google Patents
A kind of Parecoxib Sodium durative action preparation and preparation method thereof Download PDFInfo
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- CN108969494A CN108969494A CN201811115521.6A CN201811115521A CN108969494A CN 108969494 A CN108969494 A CN 108969494A CN 201811115521 A CN201811115521 A CN 201811115521A CN 108969494 A CN108969494 A CN 108969494A
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- parecoxib sodium
- preparation
- sodium
- durative action
- microballoon
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- 229960003925 parecoxib sodium Drugs 0.000 title claims abstract description 46
- ICJGKYTXBRDUMV-UHFFFAOYSA-N trichloro(6-trichlorosilylhexyl)silane Chemical compound Cl[Si](Cl)(Cl)CCCCCC[Si](Cl)(Cl)Cl ICJGKYTXBRDUMV-UHFFFAOYSA-N 0.000 title claims abstract description 46
- 238000002360 preparation method Methods 0.000 title claims abstract description 45
- 229920002037 poly(vinyl butyral) polymer Polymers 0.000 claims abstract description 17
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 claims abstract description 16
- 239000000546 pharmaceutical excipient Substances 0.000 claims abstract description 15
- 229920002785 Croscarmellose sodium Polymers 0.000 claims abstract description 13
- 229960001681 croscarmellose sodium Drugs 0.000 claims abstract description 13
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 claims abstract description 13
- 239000004094 surface-active agent Substances 0.000 claims abstract description 10
- 238000004945 emulsification Methods 0.000 claims description 20
- 239000003082 abrasive agent Substances 0.000 claims description 15
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 14
- 238000000034 method Methods 0.000 claims description 14
- 230000001804 emulsifying effect Effects 0.000 claims description 10
- 238000002156 mixing Methods 0.000 claims description 10
- 239000006185 dispersion Substances 0.000 claims description 9
- 238000000227 grinding Methods 0.000 claims description 9
- 238000003756 stirring Methods 0.000 claims description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 9
- 239000004570 mortar (masonry) Substances 0.000 claims description 8
- 239000000839 emulsion Substances 0.000 claims description 7
- 235000019441 ethanol Nutrition 0.000 claims description 7
- 238000004108 freeze drying Methods 0.000 claims description 6
- ZTQSAGDEMFDKMZ-UHFFFAOYSA-N Butyraldehyde Chemical group CCCC=O ZTQSAGDEMFDKMZ-UHFFFAOYSA-N 0.000 claims description 5
- 239000004615 ingredient Substances 0.000 claims description 5
- 238000001694 spray drying Methods 0.000 claims description 5
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 claims description 4
- 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 claims description 4
- 238000004132 cross linking Methods 0.000 claims description 4
- 239000011734 sodium Substances 0.000 claims description 4
- 229910052708 sodium Inorganic materials 0.000 claims description 4
- DWNBOPVKNPVNQG-LURJTMIESA-N (2s)-4-hydroxy-2-(propylamino)butanoic acid Chemical compound CCCN[C@H](C(O)=O)CCO DWNBOPVKNPVNQG-LURJTMIESA-N 0.000 claims description 2
- KWIUHFFTVRNATP-UHFFFAOYSA-N Betaine Natural products C[N+](C)(C)CC([O-])=O KWIUHFFTVRNATP-UHFFFAOYSA-N 0.000 claims description 2
- 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 description 2
- 229930195725 Mannitol Natural products 0.000 claims description 2
- KWIUHFFTVRNATP-UHFFFAOYSA-O N,N,N-trimethylglycinium Chemical compound C[N+](C)(C)CC(O)=O KWIUHFFTVRNATP-UHFFFAOYSA-O 0.000 claims description 2
- 229930003427 Vitamin E Natural products 0.000 claims description 2
- 229960003237 betaine Drugs 0.000 claims description 2
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 claims description 2
- 239000000594 mannitol Substances 0.000 claims description 2
- 235000010355 mannitol Nutrition 0.000 claims description 2
- 239000000203 mixture Substances 0.000 claims description 2
- 229940046009 vitamin E Drugs 0.000 claims description 2
- 235000019165 vitamin E Nutrition 0.000 claims description 2
- 239000011709 vitamin E Substances 0.000 claims description 2
- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 claims 1
- 241001412225 Firmiana simplex Species 0.000 claims 1
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 claims 1
- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 claims 1
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims 1
- 239000000835 fiber Substances 0.000 claims 1
- 239000003292 glue Substances 0.000 claims 1
- 206010003694 Atrophy Diseases 0.000 abstract description 4
- 230000037444 atrophy Effects 0.000 abstract description 4
- 230000007774 longterm Effects 0.000 abstract description 3
- 238000004321 preservation Methods 0.000 abstract description 3
- 239000003814 drug Substances 0.000 description 6
- 238000002441 X-ray diffraction Methods 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 102000010907 Cyclooxygenase 2 Human genes 0.000 description 4
- 108010037462 Cyclooxygenase 2 Proteins 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 239000001768 carboxy methyl cellulose Substances 0.000 description 3
- 238000005538 encapsulation Methods 0.000 description 3
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 3
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000004744 fabric Substances 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 2
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 2
- TZRHLKRLEZJVIJ-UHFFFAOYSA-N parecoxib Chemical compound C1=CC(S(=O)(=O)NC(=O)CC)=CC=C1C1=C(C)ON=C1C1=CC=CC=C1 TZRHLKRLEZJVIJ-UHFFFAOYSA-N 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 238000005507 spraying Methods 0.000 description 2
- 206010067484 Adverse reaction Diseases 0.000 description 1
- 241000195493 Cryptophyta Species 0.000 description 1
- 101710128782 Liver carboxylesterase Proteins 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 150000001299 aldehydes Chemical group 0.000 description 1
- 230000036592 analgesia Effects 0.000 description 1
- 230000000146 antalgic effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 208000008784 apnea Diseases 0.000 description 1
- 229940114079 arachidonic acid Drugs 0.000 description 1
- 235000021342 arachidonic acid Nutrition 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229940111134 coxibs Drugs 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- 239000003255 cyclooxygenase 2 inhibitor Substances 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 125000005909 ethyl alcohol group Chemical group 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229960004662 parecoxib Drugs 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 229940068984 polyvinyl alcohol Drugs 0.000 description 1
- 235000019422 polyvinyl alcohol Nutrition 0.000 description 1
- 230000002980 postoperative effect Effects 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/19—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles lyophilised, i.e. freeze-dried, solutions or dispersions
-
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/42—Oxazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/22—Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K47/38—Cellulose; Derivatives thereof
-
- 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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Inorganic Chemistry (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Dermatology (AREA)
- Pain & Pain Management (AREA)
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Abstract
The present invention provides a kind of Parecoxib Sodium durative action preparation and preparation method thereof, the durative action preparation includes Parecoxib Sodium, croscarmellose sodium, Karaya Gum, polyvinyl butyral, surfactant and freeze-dried excipient, the durative action preparation has extraordinary stability, can long-term preservation, and do not occur phenomena such as collapsing, atrophy during saving.
Description
Technical field
The invention belongs to field of pharmaceutical preparations, in particular to a kind of Parecoxib Sodium durative action preparation and preparation method thereof.
Background technique
SC 69124 (Parecoxib) is the novel non_steroidal anti_inflammatory drug of one kind of Pfizer Inc.'s listing
(NSAID), a kind of highly selective COX-2 inhibitors can be hydrolyzed into rapidly by liver carboxy-lesterase after intravenous injection and cut down ground
Former times cloth inhibits cyclooxygenase-2 (COX-2) that arachidonic acid synthesis prostaglandin is blocked to play anti-inflammatory and antalgic by specificity
Effect.It is to 28000 times that the inhibiting effect of COX-2 is Cycloxygenase -1 (COX-1).Due to its selective depression COX-2,
Gastrointestinal side effect, and the adverse reaction that apnea inhibits are greatly reduced, is widely used in Postoperative Analgesia After in recent years.
Parecoxib Sodium structural formula is as follows:
Injection can be made in Parecoxib Sodium, due to its stablize in water it is poor, so be generally made into freeze-dried powder,
Matching while using.Freeze-dried powder disclosed in the prior art often occurs collapsing, atrophy, occurs the problems such as more ice crystal in appearance,
Medicines structure is also possible to change in freezing dry process because of physicochemical impact simultaneously, generate unnecessary impurity and
Cause product unqualified etc..Therefore, rationally designing freeze-drying prescription makes drug be kept for long-acting the problem of being urgent need to resolve.
Summary of the invention
In order to solve the above technical problem, the present invention provides a kind of Parecoxib Sodium durative action preparation, which has
Extraordinary stability, can long-term preservation.
Specific technical solution of the present invention is as follows:
The present invention provides a kind of Parecoxib Sodium durative action preparation, which includes each ingredient of following parts by weight:
Parecoxib Sodium 5-10 croscarmellose sodium 15-23
Karaya Gum 1-2 polyvinyl butyral 10-15
Surfactant 12-20 freeze-dried excipient 10-15.
Further to improve, the Parecoxib Sodium is invisible type state.
Further to improve, the freeze-dried excipient is that weight fraction ratio is the mannitol of 7-10:2.5-4:0.5-1, sea
The mixture of algae sugar and vitamin E.
Further to improve, the surfactant is the ingredient of following parts by weight:
Phosphatidyl-4 propylhomoserin 2-5 octodecyl betaine 10-15.
It is further to improve, the Parecoxib Sodium, croscarmellose sodium, Karaya Gum and polyvinyl alcohol contracting fourth
Aldehyde forms microballoon.
Further to improve, the microballoon is prepared via a method which to obtain: by croscarmellose sodium point
It dissipates in the water of doubling dose, stirs evenly, dispersed phase is made；Karaya Gum is placed in mortar and is ground with 3000rpm, side grinding
Parecoxib Sodium is added in side, finishes, and continues to grind 10min, forms abrasive material, polyvinyl butyral and abrasive material are mixed,
The ethyl alcohol that 0.5 times of parts by weight after mixing are added forms oily phase, and dispersion is added in oily phase, and clipped machine emulsification forms cream
Change liquid, stirred with the revolving speed of 2500rpm, microballoon is made in spray drying.
Another aspect of the present invention provides a kind of preparation method of Parecoxib Sodium durative action preparation, which includes as follows
Step:
1) microballoon is prepared；
2) microballoon is uniformly mixed with surfactant and freeze-dried excipient, freeze-drying to get.
Further to improve, the Parecoxib Sodium is unformed state.
It is further to improve, the method for preparing microballoon are as follows: disperse doubling dose for croscarmellose sodium
It in water, stirs evenly, dispersed phase is made；Karaya Gum is placed in mortar and is ground with 3000rpm, pa auspicious former times is added in grinding
Cloth sodium, finishes, and continues to grind 10min, forms abrasive material, polyvinyl butyral and abrasive material are mixed, is added 0.5 after mixing
The ethyl alcohol of times parts by weight forms oily phase, and dispersion is added in oily phase, and clipped machine emulsification forms emulsion, with 2500rpm
Revolving speed stirring, spray drying, be made microballoon.
It is further to improve, the emulsification method particularly includes: first time emulsifying rate 1500rpm, time 2min, second
Secondary emulsifying rate 4500rpm, time 3min；Third time emulsification 300rpm, time 5min.
The present invention provides a kind of Parecoxib Sodium durative action preparation and preparation method thereof, which has extraordinary steady
It is qualitative, can long-term preservation, and do not occur phenomena such as collapsing, atrophy during saving.
Detailed description of the invention
Fig. 1 is the x-ray diffraction pattern of the invisible type state of Parecoxib Sodium；
Fig. 2 is the vitro release figure of Parecoxib Sodium durative action preparation.
Specific embodiment
Embodiment 1
Embodiment 2
The Parecoxib Sodium is invisible type state, and x-ray diffraction pattern is as shown in Figure 1.
Unformed state the preparation method comprises the following steps: 1g Parecoxib Sodium be added 15mL methanol in 70 DEG C heat, 70 DEG C of temperature control
5mL ethyl acetate is added, stirs 10min, is slowly cooled to 5 DEG C, the Parecoxib Sodium of unformed state is made in crystallization.
The preparation method is as follows:
By Parecoxib Sodium, croscarmellose sodium, Karaya Gum and polyvinyl butyral and surfactant
With freeze-dried excipient be uniformly mixed, freeze-drying to get.
Embodiment 3
The Parecoxib Sodium, croscarmellose sodium, Karaya Gum and polyvinyl butyral form microballoon, institute
It states microballoon to be prepared via a method which to obtain: dispersing croscarmellose sodium in the water of doubling dose, stirring is equal
It is even, dispersed phase is made；Karaya Gum is placed in mortar and is ground with 3000rpm, Parecoxib Sodium is added in grinding, finishes,
Continue to grind 10min, form abrasive material, polyvinyl butyral and abrasive material are mixed, 0.5 times of parts by weight is added after mixing
Ethyl alcohol forms oily phase, and dispersion is added in oily phase, and clipped machine emulsification is formed emulsion, stirred with the revolving speed of 2500rpm
It mixes, is spray-dried, microballoon is made；Emulsification method particularly includes: first time emulsifying rate 1500rpm, time 2min, second of cream
Change speed 4500rpm, time 3min；Third time emulsification 300rpm, time 5min.
Embodiment 4
The Parecoxib Sodium is invisible type state, and x-ray diffraction pattern is as shown in Figure 1；The Parecoxib Sodium, crosslinking
Sodium carboxymethylcellulose, Karaya Gum and polyvinyl butyral form microballoon, and the microballoon is to be prepared via a method which
To: it in the water for dispersing doubling dose for croscarmellose sodium, stirs evenly, dispersed phase is made；Karaya Gum is set
It is ground in mortar with 3000rpm, Parecoxib Sodium is added in grinding, finishes, continued to grind 10min, form abrasive material, it will
Polyvinyl butyral and abrasive material mixing, the ethyl alcohol that 0.5 times of parts by weight after mixing are added form oily phase, dispersion are added to
In oily phase, clipped machine emulsification is formed emulsion, is stirred with the revolving speed of 2500rpm, and microballoon is made in spray drying；The tool of emulsification
Body method are as follows: first time emulsifying rate 1500rpm, time 2min, second of emulsifying rate 4500rpm, time 3min；Third
Secondary emulsification 300rpm, time 5min.
Embodiment 5
The Parecoxib Sodium is invisible type state, and x-ray diffraction pattern is as shown in Figure 1；The Parecoxib Sodium, crosslinking
Sodium carboxymethylcellulose, Karaya Gum and polyvinyl butyral form microballoon.Durative action preparation the preparation method is as follows:
1) it prepares microballoon: dispersing croscarmellose sodium in the water of doubling dose, stir evenly, dispersion is made
Phase；Karaya Gum is placed in mortar and is ground with 3000rpm, Parecoxib Sodium is added in grinding, finishes, continues to grind
10min forms abrasive material, and polyvinyl butyral and abrasive material are mixed, and the ethyl alcohol that 0.5 times of parts by weight after mixing are added is formed
Dispersion is added in oily phase by oily phase, and clipped machine emulsification is formed emulsion, stirred with the revolving speed of 2500rpm, spraying dry
It is dry, microballoon is made, emulsification method particularly includes: first time emulsifying rate 1500rpm, time 2min, second of emulsifying rate
4500rpm, time 3min；Third time emulsification 300rpm, time 5min；
2) microballoon is uniformly mixed with surfactant and freeze-dried excipient, freeze-drying to get.
Embodiment 6
The Parecoxib Sodium is invisible type state, and x-ray diffraction pattern is as shown in Figure 1；The Parecoxib Sodium, crosslinking
Sodium carboxymethylcellulose, Karaya Gum and polyvinyl butyral form microballoon.Durative action preparation the preparation method is as follows:
1) it prepares microballoon: dispersing croscarmellose sodium in the water of doubling dose, stir evenly, dispersion is made
Phase；Karaya Gum is placed in mortar and is ground with 3000rpm, Parecoxib Sodium is added in grinding, finishes, continues to grind
10min forms abrasive material, and polyvinyl butyral and abrasive material are mixed, and the ethyl alcohol that 0.5 times of parts by weight after mixing are added is formed
Dispersion is added in oily phase by oily phase, and clipped machine emulsification is formed emulsion, stirred with the revolving speed of 2500rpm, spraying dry
It is dry, microballoon is made, emulsification method particularly includes: first time emulsifying rate 1500rpm, time 2min, second of emulsifying rate
4500rpm, time 3min；Third time emulsification 300rpm, time 5min；
2) microballoon is uniformly mixed with surfactant and freeze-dried excipient, freeze-drying to get.
Reference examples 1
Reference examples 2
Reference examples 3
Reference examples 4
Reference examples 5
Reference examples 6
1 durative action preparation stability experiment of experimental example
The durative action preparation of the embodiment of the present invention 1, embodiment 2,3 and reference examples 3-6 is taken, at 40 DEG C and 60 DEG C, relatively
Humidity is placed 10 days under conditions of being 75% ± 5%, 5 days and 10 days separately sampled primary, the measurement SC 69124s during test
The content (labelled amount %) of sodium, the results are shown in Table 1.
The stability experiment result of 1 durative action preparation of table
Durative action preparation provided by the invention has extraordinary stability as can be seen from the table, and do not occur collapsing,
Shrinkage phenomenon.
Influence of 2 freeze-dried excipient of experimental example to durative action preparation
This test selects different freeze-dried excipients, remaining ingredient is identical as embodiment 2, and different long-acting systems is made
The factors such as the encapsulation rate of durative action preparation, appearance, redisperse time are investigated in agent, and investigation the results are shown in Table 2.
Influence result of the different freeze-dried excipients of table 2 to durative action preparation
As can be seen from the table, the appearance for the durative action preparation for selecting freeze-dried excipient of the invention to prepare be white, it is full,
Encapsulation rate and redisperse time are good, remaining freeze-dried excipient appearance is bad, and has atrophy phenomenon, and jitter time is long, encapsulation rate
It is low.
The measurement test of 3 vitro release of experimental example
Drug release rate detection: referring to 2015 editions " Chinese Pharmacopoeia " annex XIXD vitro drug release degree inspections.
The durative action preparation for taking above embodiments 4, embodiment 5, reference examples 1 and reference examples 2 respectively, sets in medicament dissolution instrument,
In 1h, 2h, 4h, 6h, 12h, 16h, separately sampled for 24 hours, dissolution percentage is detected with high performance liquid chromatography, and calculate drug
Cumulative release percentage, is as a result shown in Fig. 2.
As can be seen from the figure the durative action preparation of embodiment 4 and embodiment 5, in interior slow release for 24 hours.
Claims (10)
1. a kind of Parecoxib Sodium durative action preparation, which is characterized in that the durative action preparation includes each ingredient of following parts by weight:
Parecoxib Sodium 5-10 croscarmellose sodium 15-23
Karaya Gum 1-2 polyvinyl butyral 10-15
Surfactant 12-20 freeze-dried excipient 10-15.
2. Parecoxib Sodium durative action preparation as described in claim 1, which is characterized in that the Parecoxib Sodium is invisible type shape
State.
3. Parecoxib Sodium durative action preparation as described in claim 1, which is characterized in that the freeze-dried excipient is parts by weight
Than the mixture for the mannitol of 7-10:2.5-4:0.5-1, trehalose and vitamin E.
4. Parecoxib Sodium durative action preparation as described in claim 1, which is characterized in that the surfactant is following weight
The ingredient of part:
Phosphatidyl-4 propylhomoserin 2-5 octodecyl betaine 10-15.
5. Parecoxib Sodium durative action preparation as described in claim 1, which is characterized in that the Parecoxib Sodium, crosslinking carboxylic first
Base sodium cellulosate, Karaya Gum and polyvinyl butyral form microballoon.
6. Parecoxib Sodium durative action preparation as claimed in claim 5, which is characterized in that the microballoon is to make by the following method
For what is obtained: dispersing croscarmellose sodium in the water of doubling dose, stir evenly, dispersed phase is made；Chinese parasol tree will be pierced
Glue is placed in mortar and is ground with 3000rpm, and Parecoxib Sodium is added in grinding, finishes, and is continued to grind 10min, is formed grinding
Object mixes polyvinyl butyral and abrasive material, and the ethyl alcohol that 0.5 times of parts by weight after mixing are added forms oily phase, by dispersed phase
It is added in oily phase, clipped machine emulsification is formed emulsion, stirred with the revolving speed of 2500rpm, and microballoon is made in spray drying.
7. a kind of preparation method of Parecoxib Sodium durative action preparation, which is characterized in that the preparation method includes the following steps:
1) microballoon is prepared；
2) microballoon is uniformly mixed with surfactant and freeze-dried excipient, freeze-drying to get.
8. preparation method as claimed in claim 7, which is characterized in that the Parecoxib Sodium is unformed state.
9. the method for claim 7, which is characterized in that the method for preparing microballoon are as follows: by cross-linked carboxymethyl fiber
Plain sodium is scattered in the water of doubling dose, is stirred evenly, and dispersed phase is made；Karaya Gum is placed in mortar and is ground with 3000rpm,
Parecoxib Sodium is added in grinding, finishes, continues to grind 10min, abrasive material is formed, by polyvinyl butyral and abrasive material
Mixing, the ethyl alcohol that 0.5 times of parts by weight after mixing are added form oily phase, dispersion are added in oily phase, clipped machine emulsification, shape
It at emulsion, is stirred with the revolving speed of 2500rpm, microballoon is made in spray drying.
10. preparation method as claimed in claim 9, which is characterized in that the emulsification method particularly includes: emulsify speed for the first time
Spend 1500rpm, time 2min, second of emulsifying rate 4500rpm, time 3min；Third time emulsification 300rpm, time 5min.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN111658620A (en) * | 2020-04-30 | 2020-09-15 | 天津医科大学口腔医院 | Hyaluronic acid-parecoxib PLGA microspheres and preparation method and application thereof |
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