CN106822057A - A kind of Oxiracetam orodispersible film and preparation method thereof - Google Patents
A kind of Oxiracetam orodispersible film and preparation method thereof Download PDFInfo
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- CN106822057A CN106822057A CN201510904201.9A CN201510904201A CN106822057A CN 106822057 A CN106822057 A CN 106822057A CN 201510904201 A CN201510904201 A CN 201510904201A CN 106822057 A CN106822057 A CN 106822057A
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- oxiracetam
- filmogen
- viscous fluid
- bubble
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- IHLAQQPQKRMGSS-UHFFFAOYSA-N oxiracetam Chemical compound NC(=O)CN1CC(O)CC1=O IHLAQQPQKRMGSS-UHFFFAOYSA-N 0.000 title claims abstract description 125
- 229960001227 oxiracetam Drugs 0.000 title claims abstract description 125
- 238000002360 preparation method Methods 0.000 title claims abstract description 45
- 239000003814 drug Substances 0.000 claims abstract description 54
- 239000000945 filler Substances 0.000 claims abstract description 38
- 239000004014 plasticizer Substances 0.000 claims abstract description 38
- 239000000463 material Substances 0.000 claims abstract description 15
- 239000012530 fluid Substances 0.000 claims description 94
- 239000007788 liquid Substances 0.000 claims description 73
- 239000006185 dispersion Substances 0.000 claims description 68
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 54
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 claims description 43
- 239000005913 Maltodextrin Substances 0.000 claims description 43
- 229920002774 Maltodextrin Polymers 0.000 claims description 43
- 229940035034 maltodextrin Drugs 0.000 claims description 43
- 235000010413 sodium alginate Nutrition 0.000 claims description 43
- 239000000661 sodium alginate Substances 0.000 claims description 43
- 229940005550 sodium alginate Drugs 0.000 claims description 43
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 39
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims description 38
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims description 38
- 239000011248 coating agent Substances 0.000 claims description 36
- 238000000576 coating method Methods 0.000 claims description 36
- 238000001035 drying Methods 0.000 claims description 36
- 229920000945 Amylopectin Polymers 0.000 claims description 35
- 239000007888 film coating Substances 0.000 claims description 35
- 238000009501 film coating Methods 0.000 claims description 35
- 239000012467 final product Substances 0.000 claims description 33
- 239000001863 hydroxypropyl cellulose Substances 0.000 claims description 33
- DOIRQSBPFJWKBE-UHFFFAOYSA-N dibutyl phthalate Chemical compound CCCCOC(=O)C1=CC=CC=C1C(=O)OCCCC DOIRQSBPFJWKBE-UHFFFAOYSA-N 0.000 claims description 24
- 235000011187 glycerol Nutrition 0.000 claims description 20
- -1 4-22 parts Chemical compound 0.000 claims description 17
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 17
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 17
- ULWHHBHJGPPBCO-UHFFFAOYSA-N propane-1,1-diol Chemical class CCC(O)O ULWHHBHJGPPBCO-UHFFFAOYSA-N 0.000 claims description 16
- 229920000881 Modified starch Polymers 0.000 claims description 15
- 239000002994 raw material Substances 0.000 claims description 14
- DOOTYTYQINUNNV-UHFFFAOYSA-N Triethyl citrate Chemical compound CCOC(=O)CC(O)(C(=O)OCC)CC(=O)OCC DOOTYTYQINUNNV-UHFFFAOYSA-N 0.000 claims description 12
- 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 description 11
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 claims description 11
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 11
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 11
- 235000013769 triethyl citrate Nutrition 0.000 claims description 11
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 10
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 claims description 10
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 claims description 10
- URAYPUMNDPQOKB-UHFFFAOYSA-N triacetin Chemical compound CC(=O)OCC(OC(C)=O)COC(C)=O URAYPUMNDPQOKB-UHFFFAOYSA-N 0.000 claims description 9
- 239000001069 triethyl citrate Substances 0.000 claims description 9
- VMYFZRTXGLUXMZ-UHFFFAOYSA-N triethyl citrate Natural products CCOC(=O)C(O)(C(=O)OCC)C(=O)OCC VMYFZRTXGLUXMZ-UHFFFAOYSA-N 0.000 claims description 9
- 229920002521 macromolecule Polymers 0.000 claims description 8
- 150000004676 glycans Chemical class 0.000 claims description 7
- 235000013773 glyceryl triacetate Nutrition 0.000 claims description 7
- 229920001282 polysaccharide Polymers 0.000 claims description 7
- 239000005017 polysaccharide Substances 0.000 claims description 7
- 239000001087 glyceryl triacetate Substances 0.000 claims description 4
- 229960002622 triacetin Drugs 0.000 claims description 4
- 229920002565 Polyethylene Glycol 400 Polymers 0.000 claims description 3
- 229920002582 Polyethylene Glycol 600 Polymers 0.000 claims description 2
- JLFNLZLINWHATN-UHFFFAOYSA-N pentaethylene glycol Chemical compound OCCOCCOCCOCCOCCO JLFNLZLINWHATN-UHFFFAOYSA-N 0.000 claims description 2
- 229940079593 drug Drugs 0.000 abstract description 13
- 238000004519 manufacturing process Methods 0.000 abstract description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 6
- 208000019505 Deglutition disease Diseases 0.000 abstract description 4
- 238000010521 absorption reaction Methods 0.000 abstract description 4
- 230000000694 effects Effects 0.000 abstract description 4
- 210000000214 mouth Anatomy 0.000 abstract description 4
- 210000003296 saliva Anatomy 0.000 abstract description 3
- 206010061623 Adverse drug reaction Diseases 0.000 abstract description 2
- 208000030453 Drug-Related Side Effects and Adverse reaction Diseases 0.000 abstract description 2
- 239000002131 composite material Substances 0.000 abstract 1
- 230000008030 elimination Effects 0.000 abstract 1
- 238000003379 elimination reaction Methods 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 30
- 229940071676 hydroxypropylcellulose Drugs 0.000 description 26
- 235000019441 ethanol Nutrition 0.000 description 22
- 125000005909 ethyl alcohol group Chemical group 0.000 description 19
- 239000000203 mixture Substances 0.000 description 17
- 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 7
- 238000004090 dissolution Methods 0.000 description 7
- 239000007924 injection Substances 0.000 description 7
- 238000002347 injection Methods 0.000 description 7
- 238000000034 method Methods 0.000 description 7
- 239000011734 sodium Substances 0.000 description 7
- 229910052708 sodium Inorganic materials 0.000 description 7
- 239000003826 tablet Substances 0.000 description 7
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 239000008279 sol Substances 0.000 description 6
- 239000002775 capsule Substances 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 239000012528 membrane Substances 0.000 description 5
- 230000008569 process Effects 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 229940084030 carboxymethylcellulose calcium Drugs 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 229920002472 Starch Polymers 0.000 description 3
- 235000010980 cellulose Nutrition 0.000 description 3
- 229920002678 cellulose Polymers 0.000 description 3
- 239000001913 cellulose Substances 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 239000002502 liposome Substances 0.000 description 3
- 239000000314 lubricant Substances 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 239000008107 starch Substances 0.000 description 3
- 235000019698 starch Nutrition 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- KRQUFUKTQHISJB-YYADALCUSA-N 2-[(E)-N-[2-(4-chlorophenoxy)propoxy]-C-propylcarbonimidoyl]-3-hydroxy-5-(thian-3-yl)cyclohex-2-en-1-one Chemical compound CCC\C(=N/OCC(C)OC1=CC=C(Cl)C=C1)C1=C(O)CC(CC1=O)C1CCCSC1 KRQUFUKTQHISJB-YYADALCUSA-N 0.000 description 2
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 2
- 206010011224 Cough Diseases 0.000 description 2
- XTXRWKRVRITETP-UHFFFAOYSA-N Vinyl acetate Chemical group CC(=O)OC=C XTXRWKRVRITETP-UHFFFAOYSA-N 0.000 description 2
- 238000004026 adhesive bonding Methods 0.000 description 2
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 235000009508 confectionery Nutrition 0.000 description 2
- 239000007884 disintegrant Substances 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 239000004519 grease Substances 0.000 description 2
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 2
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 230000002572 peristaltic effect Effects 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- ILJSQTXMGCGYMG-UHFFFAOYSA-N triacetic acid Chemical compound CC(=O)CC(=O)CC(O)=O ILJSQTXMGCGYMG-UHFFFAOYSA-N 0.000 description 2
- QVPLPSZGHFSYEQ-UHFFFAOYSA-N 2-amino-2-hydroxybutanoic acid Chemical compound CCC(N)(O)C(O)=O QVPLPSZGHFSYEQ-UHFFFAOYSA-N 0.000 description 1
- 229920002785 Croscarmellose sodium Polymers 0.000 description 1
- 206010013710 Drug interaction Diseases 0.000 description 1
- 206010013786 Dry skin Diseases 0.000 description 1
- 206010018873 Haemoconcentration Diseases 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 208000035868 Vascular inflammations Diseases 0.000 description 1
- 235000019888 Vivapur Nutrition 0.000 description 1
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
- VEUACKUBDLVUAC-UHFFFAOYSA-N [Na].[Ca] Chemical compound [Na].[Ca] VEUACKUBDLVUAC-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- 229940125682 antidementia agent Drugs 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 235000019658 bitter taste Nutrition 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 229940063834 carboxymethylcellulose sodium Drugs 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 238000004581 coalescence Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 239000007919 dispersible tablet Substances 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 239000009322 erkang Substances 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 239000010419 fine particle Substances 0.000 description 1
- YQGDEPYYFWUPGO-UHFFFAOYSA-N gamma-amino-beta-hydroxybutyric acid Chemical class [NH3+]CC(O)CC([O-])=O YQGDEPYYFWUPGO-UHFFFAOYSA-N 0.000 description 1
- 239000003292 glue Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 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 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 239000002932 luster Substances 0.000 description 1
- 238000003760 magnetic stirring Methods 0.000 description 1
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000000465 moulding Methods 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 239000002664 nootropic agent Substances 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 238000011056 performance test Methods 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 208000009146 rhinoscleroma Diseases 0.000 description 1
- 239000004576 sand Substances 0.000 description 1
- 238000007493 shaping process Methods 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- 229960002675 xylitol Drugs 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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
- A61K9/006—Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
- A61J3/00—Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms
-
- 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
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/4015—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil having oxo groups directly attached to the heterocyclic ring, e.g. piracetam, ethosuximide
-
- 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
-
- 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
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
- A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
Landscapes
- 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)
- Inorganic Chemistry (AREA)
- Nutrition Science (AREA)
- Physiology (AREA)
- Zoology (AREA)
- Medicinal Preparation (AREA)
Abstract
A kind of Oxiracetam orodispersible film, is obtained using materials such as composite membrane-forming material, plasticizer, fillers；Oxiracetam orodispersible film of the present invention, it is that can dissolve with a small amount of saliva in oral cavity, and medication by being not required to water delivery service, medication is convenient；And be difficult to spue after adhering on the tongue, it is adapted to the patient of dysphagia, and by mucosal absorption, it is to avoid first to cross elimination effect, bioavilability is improve, pharmaceutical dosage is reduced, so as to reduce drug side-effect.Preparation process is simple of the present invention, is adapted to industrialized production.
Description
Technical field
The present invention relates to Oxiracetam, and in particular to a kind of Oxiracetam orodispersible film and its
Preparation method.
Background technology
Oxiracetam (Oxiracetam), chemical entitled 4- hydroxyls -2- OXo-1-pyrrolidines
Acetamide, be by Italian SmithKline than the cereboactive drug that Qie Mu company synthesized first in 1974,
It is a kind of hydroxy-amino-butyric acid (GABOB) derivative, study can be promoted, strengthen memory, protects
Protect the medicine for central nervous system of damaged nerve cell.Its structure is as follows：
Since being put on market from it, worked well due to it, safe, indication scope is wide,
Drug interaction is few and the low feature of toxicity, is always to treat the leading product in anti-dementia agent
Product, injection, capsule, tablets and other formulations develop listing in succession.
CN104069074A discloses a kind of Oxiracetam injection lyophilized formulations, and said preparation is for first
Oxiracetam is formed into the certain density aqueous solution, methyl alcohol is subsequently adding lyophilized prepared；This is freezed
Preparation is substantially free of auxiliary material, and redissolution is rapid, quality is good, storage is stable.Such preparation is directly noted
Enter tissue or blood vessel, it is very short without absorption process or absorption process, thus haemoconcentration can arrive rapidly
Played a role up to peak；But it is developed and production process is complicated, because injection requirement is aseptic
Apyrogeneity, production process is strict, and step is more to need appointed condition higher, and injection
Middle medicine is generally dispersed in water with the micron-sized solid small particles of molecular state, and decentralization is very
Greatly, and drug hydrolysis, oxidation, solids coalescence is often produced to become big by high-temperature sterilization
Equistability problem.Simultaneously because injection directly quickly enters human body, without human body normal physiological
The protection of barrier, if therefore dosage is improper or inject too fast, or there is problem in drug quality,
It is possible to bring harm to patient, or even causes the consequence that cannot be retrieved.In addition injection pain,
Scleroma and intravenous injection can not be produced to cause vascular inflammation by patient's self-administer, injection site
The problem existed when being all clinical practice.
CN101732251A discloses a kind of oxiracetam liposome, by Oxiracetam, phosphatide,
Cholesterol, Tween 80 and appropriate osmotic pressure regulator and cushioning liquid are obtained；The lipid
Body good stability, envelop rate are high, toxic and side effect is small；But liposome preparation complex process, no
It is adapted to large-scale production；Curative effect of the what is more important liposome in human body need further
Study, the current country rarely has Liposomal formulation for clinic.
CN103494790A discloses a kind of oxiracetam capsule, by xylitol, lubricant and
The Oxiracetam of crystal form is obtained；Obtained oxiracetam capsule quality stability is significantly carried
Height, preparation process is simple, production cost reduction.CN104739796A discloses a kind of Aura
Western smooth tablet, by a certain amount of Oxiracetam, filler, disintegrant, binder and lubricant
It is obtained；The tablets, carry, and transport and storage are all more convenient.But in actual clinical,
Capsule, tablet are choked and cough event often, and the patient of feeblemindedness is in the majority with the elderly,
This kind of patient takes oxiracetam capsule agent, tablet very not usually for medicine dysphagia
Just.
CN1555794A discloses a kind of Orazitan dispersion tablet, by Oxiracetam, disintegrant,
Lubricant and glidant and adhesive are obtained, and can be promptly disintegrated into after the medicine is oral dispersed
Fine particle, be conducive to drug-eluting to absorb；It is convenient to take, it is oral after the dispersion that can add water,
Can be contained in mouth and suck clothes or swallow.Oral dispersable tablet equally exists the problem choked and cough, and suckes
Dispersible tablet is taken, it works very slowly, and there is sand type and bitter taste, is unfavorable for taking.
The content of the invention
In order to overcome the shortcoming of prior art, the present invention to provide a kind of Oxiracetam orodispersible film
Agent, the film is that can dissolve with a small amount of saliva in oral cavity, medication by being not required to water delivery service,
Medication is convenient；And be difficult to spue after being adhered on tongue, it is adapted to the patient of dysphagia.
Unless otherwise specified, number of the present invention is weight portion.
The object of the present invention is achieved like this：
A kind of Oxiracetam orodispersible film, by the Oxiracetam including 4-22 parts, 42-76
Part filmogen, 10-38 part of filler and 8-36 parts of plasticizer it is prepared in interior raw material；
The filmogen is comprising maltodextrin and at least another macromolecule filming material；It is described another
A kind of macromolecule filming material is selected from hydroxypropyl cellulose, amylopectin, sodium alginate, Pu Lu
Blue polysaccharide, PVP-vinyl acetate or sodium carboxymethylcellulose；The plasticizer be selected from glycerine,
Propane diols, glyceryl triacetate, triethyl citrate, dibutyl phthalate, PEG400
With the one or more combination in PEG600；The filler is selected from microcrystalline cellulose, low takes
For one or more in hydroxypropyl cellulose, pregelatinized starch, Ac-Di-Sol
Combination.
Inventor has found that the Oxiracetam orodispersible film quality of preparation is not in R＆D process
Stabilization, the problems such as easily occurring that matter is soft, filming performance is poor, be difficult to the demoulding.
An embodiment of the invention,
A kind of Oxiracetam orodispersible film, by the Oxiracetam including 8-20 parts, 45-70
Part filmogen, 15-32 parts of filler and 10-33 parts of plasticizer in interior raw material system
；The filmogen is comprising maltodextrin and at least another macromolecule filming material；Institute
State another macromolecule filming material be selected from hydroxypropyl cellulose, amylopectin, sodium alginate,
Pulullan polysaccharide, PVP-vinyl acetate or sodium carboxymethylcellulose, wherein hydroxy propyl cellulose
Element, amylopectin, sodium alginate, pulullan polysaccharide, PVP-vinyl acetate or carboxymethyl
The consumption of sodium cellulosate is respectively：5 parts~40 parts, 10~15 parts, 3~15 parts, 1~5
Part, 12~18 parts, 5~18 parts.
An embodiment of the invention,
A kind of Oxiracetam orodispersible film, by the Oxiracetam including 8-20 parts, 45-65
Part filmogen, 15-30 parts of filler and 15-25 parts of plasticizer in interior raw material system
；The filmogen is that maltodextrin and hydroxypropyl cellulose are combined, wherein hydroxypropyl
Cellulose consumption is 10 parts~30 parts；The filler is microcrystalline cellulose or low-substituted hydroxypropyl
Base cellulose；The plasticizer is the one kind in glycerine, propane diols or triethyl citrate.
An embodiment of the invention,
A kind of Oxiracetam orodispersible film, by the Oxiracetam including 8-18 parts, 45-60
Part filmogen, 15-25 parts of filler and 10-25 parts of plasticizer in interior raw material system
；The filmogen is that maltodextrin and amylopectin are constituted, and wherein amylopectin consumption is
11 parts~15 parts；The filler is low-substituted hydroxypropyl cellulose or pregelatinized starch；Institute
Plasticizer is stated for propane diols or dibutyl phthalate.
An embodiment of the invention,
A kind of Oxiracetam orodispersible film, by the Oxiracetam including 8-20 parts, 50-70
Part filmogen, 15-25 parts of filler and 10-25 parts of plasticizer in interior raw material system
；The filmogen is that maltodextrin and sodium alginate are constituted, and wherein sodium alginate consumption is
8 parts~15 parts；The filler is low-substituted hydroxypropyl cellulose or cross-linked carboxymethyl cellulose
Sodium；The plasticizer is glycerine or dibutyl phthalate.
An embodiment of the invention,
A kind of Oxiracetam orodispersible film, by the Oxiracetam including 8-15 parts, 50-70
Part filmogen, 15-25 parts of filler and 15-20 parts of plasticizer in interior raw material system
；The filmogen is maltodextrin, hydroxypropyl cellulose and sodium carboxymethylcellulose composition,
Wherein hydroxypropyl cellulose consumption is 5 parts~20 parts, and sodium carboxymethylcellulose consumption is 5~15
Part；The filler is microcrystalline cellulose or Ac-Di-Sol；The plasticizer is
One kind in propane diols or triethyl citrate.
An embodiment of the invention,
A kind of Oxiracetam orodispersible film, by the Oxiracetam including 9-15 parts, 45-65
Part filmogen, 15-28 parts of filler and 15-25 parts of plasticizer in interior raw material system
；The filmogen is maltodextrin, sodium alginate and PVP-vinyl acetate composition,
Wherein sodium alginate consumption is 3 parts~10 parts, and PVP-vinyl acetate consumption is 15~18
Part；The filler is microcrystalline cellulose or pregelatinized starch；The plasticizer is that triacetic acid is sweet
Grease or dibutyl phthalate.
An embodiment of the invention,
A kind of Oxiracetam orodispersible film, by the Oxiracetam including 10-20 parts, 45-60
Part filmogen, 10-30 parts of filler and 10-25 parts of plasticizer in interior raw material system
；The filmogen is maltodextrin, amylopectin and sodium alginate composition, wherein side chain
Starch consumption is 12 parts~15 parts, and sodium alginate consumption is 3 parts~10 parts；The filler
It is pregelatinized starch or Ac-Di-Sol；The plasticizer is that glycerine or triacetic acid are sweet
Grease.
The present invention provides the preparation method of above-mentioned Oxiracetam orodispersible film, the method operation
Simply, it is adapted to industrialized production.
The preparation method of above-mentioned Oxiracetam orodispersible film, using following steps：
1) by filmogen anhydrous alcohol solution, slough bubble and uniform viscous fluid is obtained；
2) plasticizer, filler absolute ethyl alcohol are uniformly dispersed into dispersion liquid；
3) by step 2) dispersion liquid be added to step 1) viscous fluid in, and add Aura
It is western it is smooth be uniformly dispersed, then stand slough bubble；
4) the medicine film coating dryer of the viscous fluid after bubble will be removed to be coated with, dry, peel off
Obtain final product.
Above-mentioned steps 1), step 2) in absolute ethyl alcohol consumption according to actual conditions by ability
Domain those of ordinary skill determines.
An embodiment of the invention,
A kind of preparation method of Oxiracetam orodispersible film, using following steps：
1) by 40-70 parts of filmogen anhydrous alcohol solution, slough bubble and be obtained uniformly
Viscous fluid；
2) 10-33 parts of plasticizer, 15-32 parts of filler are uniformly dispersed with absolute ethyl alcohol
Into dispersion liquid；
3) by step 2) dispersion liquid be added to step 1) viscous fluid in, and add 8-20
The Oxiracetam of part is uniformly dispersed, and then stands and sloughs bubble；
4) the medicine film coating dryer of the viscous fluid after bubble will be removed to be coated with, dry, peel off
Obtain final product.
In order to strengthen patient adaptability, and disintegration time limited of the invention is rationally controlled, the present invention is difficult to understand
The thickness of La Xitan orodispersible films is 80~120 μm.
In order to further improve the quality of Oxiracetam orodispersible film of the present invention, above-mentioned medicine film
The coating speed of drying machine is 60-85cm/min, and drying temperature is 70-90 DEG C.
An embodiment of the invention,
A kind of preparation method of Oxiracetam orodispersible film, using following steps：
1) by 45-65 parts of filmogen (maltodextrin and hydroxypropyl cellulose are constituted, wherein
Hydroxypropyl cellulose consumption is 10 parts~30 parts) anhydrous alcohol solution is used, slough bubble and be obtained
Even viscous fluid；
2) by 15-25 parts of plasticizer (glycerine, propane diols or triethyl citrate), 15-30
The filler (microcrystalline cellulose or low-substituted hydroxypropyl cellulose) of part absolute ethyl alcohol disperses equal
It is even into dispersion liquid；
3) by step 2) dispersion liquid be added to step 1) viscous fluid in, and add 8-20
The Oxiracetam of part is uniformly dispersed, and then stands and sloughs bubble；
4) viscous fluid after bubble will be removed to be coated with medicine film coating dryer, coating speed is
60-85cm/min, then with 70-90 DEG C of drying, stripping is obtained final product.
An embodiment of the invention,
A kind of preparation method of Oxiracetam orodispersible film, using following steps：
1) by 45-60 parts of filmogen, (maltodextrin and amylopectin are constituted, wherein side chain
Starch consumption is 11 parts~15 parts) anhydrous alcohol solution is used, slough bubble prepared uniform sticky
Liquid；
2) by 10-25 parts of plasticizer (propane diols or dibutyl phthalate), 15-25
The filler (low-substituted hydroxypropyl cellulose or pregelatinized starch) of part absolute ethyl alcohol disperses equal
It is even into dispersion liquid；
3) by step 2) dispersion liquid be added to step 1) viscous fluid in, and add 8-18
The Oxiracetam of part is uniformly dispersed, and then stands and sloughs bubble；
4) viscous fluid after bubble will be removed to be coated with medicine film coating dryer, coating speed is
60-80cm/min, then with 70-85 DEG C of drying, stripping is obtained final product.
An embodiment of the invention,
A kind of preparation method of Oxiracetam orodispersible film, using following steps：
1) by 50-70 parts of filmogen, (maltodextrin and sodium alginate are constituted, wherein marine alga
Sour sodium consumption is 8 parts~15 parts) anhydrous alcohol solution is used, slough bubble prepared uniform sticky
Liquid；
2) by 10-25 parts of plasticizer (glycerine or dibutyl phthalate), 15-25 parts
Filler (low-substituted hydroxypropyl cellulose or Ac-Di-Sol) use absolute ethyl alcohol
It is uniformly dispersed into dispersion liquid；
3) by step 2) dispersion liquid be added to step 1) viscous fluid in, and add 8-20
The Oxiracetam of part is uniformly dispersed, and then stands and sloughs bubble；
4) viscous fluid after bubble will be removed to be coated with medicine film coating dryer, coating speed is
60-78cm/min, then with 70-85 DEG C of drying, stripping is obtained final product.
An embodiment of the invention,
A kind of preparation method of Oxiracetam orodispersible film, using following steps：
1) by 50-70 parts of filmogen, (maltodextrin, hydroxypropyl cellulose and carboxymethyl are fine
The plain sodium composition of dimension, wherein hydroxypropyl cellulose consumption be 5 parts~20 parts, carboxymethylcellulose calcium
Sodium consumption is 5~15 parts) anhydrous alcohol solution is used, slough bubble and uniform viscous fluid is obtained；
2) by 15-20 parts of plasticizer (propane diols or triethyl citrate), 15-25 parts
Filler (microcrystalline cellulose or Ac-Di-Sol) is uniformly dispersed into absolute ethyl alcohol
Dispersion liquid；
3) by step 2) dispersion liquid be added to step 1) viscous fluid in, and add 8-15
The Oxiracetam of part is uniformly dispersed, and then stands and sloughs bubble；
4) viscous fluid after bubble will be removed to be coated with medicine film coating dryer, coating speed is
60-75cm/min, then with 70-85 DEG C of drying, stripping is obtained final product.
An embodiment of the invention,
A kind of preparation method of Oxiracetam orodispersible film, using following steps：
1) by 45-65 parts of filmogen (maltodextrin, sodium alginate and PVP-acetic acid second
Alkene is constituted, and wherein sodium alginate consumption is 3 parts~10 parts, and PVP-vinyl acetate consumption is
15~18 parts) anhydrous alcohol solution is used, slough bubble and uniform viscous fluid is obtained；
2) by 15-25 parts of plasticizer (glyceryl triacetate or dibutyl phthalate),
15-28 parts of filler (microcrystalline cellulose or pregelatinized starch) is uniformly dispersed with absolute ethyl alcohol
Into dispersion liquid；
3) by step 2) dispersion liquid be added to step 1) viscous fluid in, and add 9-15
The Oxiracetam of part is uniformly dispersed, and then stands and sloughs bubble；
4) viscous fluid after bubble will be removed to be coated with medicine film coating dryer, coating speed is
60-80cm/min, then with 70-90 DEG C of drying, stripping is obtained final product.
An embodiment of the invention,
A kind of preparation method of Oxiracetam orodispersible film, using following steps：
1) by 45-60 parts of filmogen (maltodextrin, amylopectin and sodium alginate composition,
Wherein amylopectin consumption is 12 parts~15 parts, and sodium alginate consumption is 3 parts~10 parts) use
Anhydrous alcohol solution, sloughs bubble and uniform viscous fluid is obtained；
2) 10-25 parts of plasticizer (glycerine or glyceryl triacetate), 10-30 parts are filled out
Agent (pregelatinized starch or Ac-Di-Sol) absolute ethyl alcohol is filled to be uniformly dispersed composition
Dispersion liquid；
3) by step 2) dispersion liquid be added to step 1) viscous fluid in, and add 10-20
The Oxiracetam of part is uniformly dispersed, and then stands and sloughs bubble；
4) viscous fluid after bubble will be removed to be coated with medicine film coating dryer, coating speed is
60-80cm/min, then with 70-85 DEG C of drying, stripping is obtained final product.
The invention has the advantages that：
1st, Oxiracetam orodispersible film prepared by the present invention, it uses a small amount of saliva in oral cavity
Liquid is that can dissolve, and medication by being not required to water delivery service, medication is convenient；And after being adhered on tongue not
Easily spue, be adapted to the patient of dysphagia, and by mucosal absorption, it is to avoid first mistake eliminates
Effect, improves bioavilability, reduces pharmaceutical dosage, so as to reduce drug side-effect.
2nd, the Oxiracetam of present invention selection specified quantitative, filmogen, filler and plasticizer
It is combined, and selection maltodextrin and at least another macromolecular material (hydroxypropyl fibre meticulously
Dimension element, amylopectin, sodium alginate, pulullan polysaccharide, PVP-vinyl acetate or carboxylic first
Base sodium cellulosate) compound film material is formed, it is easy so as to solve Oxiracetam orodispersible film
Appearance matter is soft, filming performance is poor, be difficult to the technical problems such as the demoulding, so as to improve product quality.
The present invention is by specific compound film material, the combination of plasticizer and filler, so as to solve system
Standby Oxiracetam orodispersible film mechanical performance is bad, disintegration time is long, film has fragility,
The technical problem such as it is easily broken off, so as to ensure that product quality.
3rd, the present invention prepares Oxiracetam orodispersible film using medicine film film applicator, and strictly
Thickness, coating speed and the drying temperature of film are controlled, so as to stabilize technique, it is ensured that
The quality of product so that the aspect such as fragility of the invention, disintegration time limited and solution time is more sharp
In clinical practice；And preparation method of the present invention is simple, it is not necessary to large industry equipment, it is adapted to
Industrialized production.
Embodiment
In order that the purpose of the present invention and technical scheme are clearer, below to of the invention preferred
Embodiment is described in detail.To illustrate that：Following examples are served only for entering the present invention
Row further instruction, and it is not intended that limiting the scope of the invention.This area
Some nonessential modifications and adaptations that technical staff's the above of the invention is made are equal
Belong to protection scope of the present invention.
The present invention is raw materials used to be commercially available prod with reagent.Wherein Oxiracetam raw material (content
99.8%, Chongqing Dongze Pharmaceutical Technology Development Co., Ltd. provides, and lot number is：20140917)；
Hydroxypropyl methylcellulose (HPMC, Dow Chemical company, specification E50)；Hydroxypropyl is fine
Dimension is plain (HPC, Ashland companies of the U.S., specification LF)；Sodium alginate (Shandong Fu Ruida
Bio tech ltd)；Polyethylene glycol (PEG) 400 (Hunan Hua pharmaceutical Co. Ltds)；
Glycerine (Hu'nan Erkang Pharmaceutical Co., Ltd.)；Triethyl citrate (TEC, Bang Bufeng
Former medical sci-tech Development Co., Ltd)；Low-substituted hydroxypropyl cellulose (L-HPC), pre- glue
Change starch (Anhui Shanhe Medicinal Subsidiary Material Co., Ltd.)；Microcrystalline cellulose (MCC, moral
JRS companies of state, specification VIVAPUR 101)；Acetonitrile, methyl alcohol are chromatographically pure, other reagents
It is pure to analyze.
Medicine film coating dryer used of the invention is commercially available prod, it is also possible to reference to CN
201668734 U make by oneself, and medicine film coating dryer is by main box, auxiliary box body, peristaltic pump, flat
Plate scraper, master roller, deputy roller cylinder, conveyer belt, heating electroplax, induced-draught fan and rolling-up mechanism group
Into.Its action principle is added on a moving belt for drug slurry by peristaltic pump, and conveyer belt is in motor
Under drive, around main box operating, the liquid on conveyer belt is hung into film by flat scraper, plus
Thermoelectric plate air is heated, and induced-draught fan takes the air in main box away, makes air in main box
Interior flowing, the solvent of liquid is flung to, drying and moulding, and rolling-up mechanism collects the medicine film of shaping.
Embodiment 1
The preparation of Oxiracetam orodispersible film, using following steps：
1) by 60g filmogens, (maltodextrin and hydroxypropyl cellulose are constituted, wherein hydroxypropyl
Cellulose consumption is 30g) 80mL anhydrous alcohol solutions are used, slough bubble prepared uniform sticky
Liquid；
2) 20g glycerine, 15g microcrystalline celluloses 50mL absolute ethyl alcohols are uniformly dispersed composition
Dispersion liquid；
3) by step 2) dispersion liquid be added to step 1) viscous fluid in, and add 8g
Oxiracetam is uniformly dispersed, and then stands and sloughs bubble；
4) viscous fluid after bubble will be removed to be coated with medicine film coating dryer, coating speed is
60cm/min, then with 75-77 DEG C of drying, stripping is obtained final product.
Embodiment 2
The preparation of Oxiracetam orodispersible film, using following steps：
1) by the filmogen of 45g, (maltodextrin and hydroxypropyl cellulose are constituted, wherein hydroxypropyl
Base cellulose consumption is 10g) 50mL anhydrous alcohol solutions are used, slough bubble and uniform gluing is obtained
Magma；
2) by 20g propane diols, 22g low-substituted hydroxypropyl celluloses 60mL absolute ethyl alcohols point
Dissipate non-uniform components dispersion liquid；
3) by step 2) dispersion liquid be added to step 1) viscous fluid in, and add 18g
Oxiracetam be uniformly dispersed, then stand slough bubble；
4) viscous fluid after bubble will be removed to be coated with medicine film coating dryer, coating speed is
80cm/min, then with 70-72 DEG C of drying, stripping is obtained final product.
Embodiment 3
The preparation of Oxiracetam orodispersible film, using following steps：
1) by the filmogen of 50g, (maltodextrin and hydroxypropyl cellulose are constituted, wherein hydroxypropyl
Base cellulose consumption is 20g) 50mL anhydrous alcohol solutions are used, slough bubble and uniform gluing is obtained
Magma；
2) 15g triethyl citrates, 20g microcrystalline celluloses are disperseed with 40mL absolute ethyl alcohols
Non-uniform components dispersion liquid；
3) by step 2) dispersion liquid be added to step 1) viscous fluid in, and add 15g
Oxiracetam be uniformly dispersed, then stand slough bubble；
4) viscous fluid after bubble will be removed to be coated with medicine film coating dryer, coating speed is
70cm/min, then with 83-85 DEG C of drying, stripping is obtained final product.
Embodiment 4
The preparation of Oxiracetam orodispersible film, using following steps：
1) by the filmogen of 60g, (maltodextrin and amylopectin are constituted, wherein amylopectin
Consumption is 15g) 80mL anhydrous alcohol solutions are used, slough bubble and uniform viscous fluid is obtained；
2) by 15g propane diols, 15g low-substituted hydroxypropyl celluloses 30mL absolute ethyl alcohols point
Dissipate non-uniform components dispersion liquid；
3) by step 2) dispersion liquid be added to step 1) viscous fluid in, and add 15g
Oxiracetam is uniformly dispersed, and then stands and sloughs bubble；
4) viscous fluid after bubble will be removed to be coated with medicine film coating dryer, coating speed is
65cm/min, then with 70-72 DEG C of drying, stripping is obtained final product.
Embodiment 5
The preparation of Oxiracetam orodispersible film, using following steps：
1) by the filmogen of 45g, (maltodextrin and amylopectin are constituted, wherein amylopectin
Consumption is 11g) anhydrous alcohol solution is used, slough bubble and uniform viscous fluid is obtained；
2) by 25g dibutyl phthalates, 22g pregelatinized starch 60mL absolute ethyl alcohols
It is uniformly dispersed into dispersion liquid；
3) by step 2) dispersion liquid be added to step 1) viscous fluid in, and add 18g
Oxiracetam be uniformly dispersed, then stand slough bubble；
4) viscous fluid after bubble will be removed to be coated with medicine film coating dryer, coating speed is
70cm/min, then with 75-78 DEG C of drying, stripping is obtained final product.
Embodiment 6
The preparation of Oxiracetam orodispersible film, using following steps：
1) by the filmogen of 45g, (maltodextrin and amylopectin are constituted, wherein amylopectin
Consumption is 12g) 55mL anhydrous alcohol solutions are used, slough bubble and uniform viscous fluid is obtained；
2) by 18g dibutyl phthalates, 25g pregelatinized starch 45mL absolute ethyl alcohols
It is uniformly dispersed into dispersion liquid；
3) by step 2) dispersion liquid be added to step 1) viscous fluid in, and add 12g
Oxiracetam be uniformly dispersed, then stand slough bubble；
4) viscous fluid after bubble will be removed to be coated with medicine film coating dryer, coating speed is
80cm/min, then with 80-82 DEG C of drying, stripping is obtained final product.
Embodiment 7
The preparation of Oxiracetam orodispersible film, using following steps：
1) by the filmogen of 70g, (maltodextrin and sodium alginate are constituted, wherein sodium alginate
Consumption is 15g) 80mL anhydrous alcohol solutions are used, slough bubble and uniform viscous fluid is obtained；
2) 10g glycerine, 15g low-substituted hydroxypropyl celluloses are disperseed with 30mL absolute ethyl alcohols
Non-uniform components dispersion liquid；
3) by step 2) dispersion liquid be added to step 1) viscous fluid in, and add 8g
Oxiracetam be uniformly dispersed, then stand slough bubble；
4) viscous fluid after bubble will be removed to be coated with medicine film coating dryer, coating speed is
65cm/min, then with 76-78 DEG C of drying, stripping is obtained final product.
Embodiment 8
The preparation of Oxiracetam orodispersible film, using following steps：
1) by the filmogen of 50g, (maltodextrin and sodium alginate are constituted, wherein sodium alginate
Consumption is 8g) 65mL anhydrous alcohol solutions are used, slough bubble and uniform viscous fluid is obtained；
2) by 20g dibutyl phthalates, 15g Ac-Di-Sols 50mL
Absolute ethyl alcohol is uniformly dispersed into dispersion liquid；
3) by step 2) dispersion liquid be added to step 1) viscous fluid in, and add 18g
Oxiracetam be uniformly dispersed, then stand slough bubble；
4) viscous fluid after bubble will be removed to be coated with medicine film coating dryer, coating speed is
70cm/min, then with 70-72 DEG C of drying, stripping is obtained final product.
Embodiment 9
The preparation of Oxiracetam orodispersible film, using following steps：
1) by the filmogen of 60g, (maltodextrin and sodium alginate are constituted, wherein sodium alginate
Consumption is 12g) 65mL anhydrous alcohol solutions are used, slough bubble and uniform viscous fluid is obtained；
2) 10g glycerine, 15g low-substituted hydroxypropyl celluloses are disperseed with 35mL absolute ethyl alcohols
Non-uniform components dispersion liquid；
3) by step 2) dispersion liquid be added to step 1) viscous fluid in, and add 15g
Oxiracetam be uniformly dispersed, then stand slough bubble；
4) viscous fluid after bubble will be removed to be coated with medicine film coating dryer, coating speed is
78cm/min, then with 83-85 DEG C of drying, stripping is obtained final product.
Embodiment 10
The preparation of Oxiracetam orodispersible film, using following steps：
1) by filmogen (maltodextrin, hydroxypropyl cellulose and the carboxymethylcellulose calcium of 50g
Sodium is constituted, and wherein hydroxypropyl cellulose consumption is 5g, and sodium carboxymethylcellulose consumption is 5g)
50mL anhydrous alcohol solutions are used, bubble is sloughed and uniform viscous fluid is obtained；
2) 15g propane diols, 25g microcrystalline celluloses are uniformly dispersed into 50mL absolute ethyl alcohols
Dispersion liquid；
3) by step 2) dispersion liquid be added to step 1) viscous fluid in, and add 10g
Oxiracetam be uniformly dispersed, then stand slough bubble；
4) viscous fluid after bubble will be removed to be coated with medicine film coating dryer, coating speed is
60cm/min, then with 80-82 DEG C of drying, stripping is obtained final product.
Embodiment 11
The preparation of Oxiracetam orodispersible film, using following steps：
1) by filmogen (maltodextrin, hydroxypropyl cellulose and the carboxymethylcellulose calcium of 60g
Sodium is constituted, and wherein hydroxypropyl cellulose consumption is 20g, and sodium carboxymethylcellulose consumption is 15g)
80mL anhydrous alcohol solutions are used, bubble is sloughed and uniform viscous fluid is obtained；
2) it is 16g triethyl citrates, 25g Ac-Di-Sols is anhydrous with 50mL
Ethanol is uniformly dispersed into dispersion liquid；
3) by step 2) dispersion liquid be added to step 1) viscous fluid in, and add 10g
Oxiracetam be uniformly dispersed, then stand slough bubble；
4) viscous fluid after bubble will be removed to be coated with medicine film coating dryer, coating speed is
75cm/min, then with 70-72 DEG C of drying, stripping is obtained final product.
Embodiment 12
The preparation of Oxiracetam orodispersible film, using following steps：
1) by filmogen (maltodextrin, hydroxypropyl cellulose and the carboxymethylcellulose calcium of 60g
Sodium is constituted, and wherein hydroxypropyl cellulose consumption is 10g, and sodium carboxymethylcellulose consumption is 10g)
65mL anhydrous alcohol solutions are used, bubble is sloughed and uniform viscous fluid is obtained；
2) 15g propane diols, 20g microcrystalline celluloses are uniformly dispersed into 40mL absolute ethyl alcohols
Dispersion liquid；
3) by step 2) dispersion liquid be added to step 1) viscous fluid in, and add 8g
Oxiracetam is uniformly dispersed, and then stands and sloughs bubble；
4) viscous fluid after bubble will be removed to be coated with medicine film coating dryer, coating speed is
70cm/min, then with 75-78 DEG C of drying, stripping is obtained final product.
Embodiment 13
The preparation of Oxiracetam orodispersible film, using following steps：
1) by filmogen (maltodextrin, sodium alginate and PVP-the vinyl acetate group of 45g
Into wherein sodium alginate consumption is 3g, and PVP-vinyl acetate consumption is 15g) use 50mL
Anhydrous alcohol solution, sloughs bubble and uniform viscous fluid is obtained；
2) 15g glyceryl triacetates, 25g microcrystalline celluloses are disperseed with 50mL absolute ethyl alcohols
Non-uniform components dispersion liquid；
3) by step 2) dispersion liquid be added to step 1) viscous fluid in, and add 15g
Oxiracetam be uniformly dispersed, then stand slough bubble；
4) viscous fluid after bubble will be removed to be coated with medicine film coating dryer, coating speed is
80cm/min, then with 85-90 DEG C of drying, stripping is obtained final product.
Embodiment 14
The preparation of Oxiracetam orodispersible film, using following steps：
1) by filmogen (maltodextrin, sodium alginate and PVP-the vinyl acetate group of 65g
Into wherein sodium alginate consumption is 10g, and PVP-vinyl acetate consumption is 18g) use 70mL
Anhydrous alcohol solution, sloughs bubble and uniform viscous fluid is obtained；
2) by 15g dibutyl phthalates, 20g pregelatinized starch 30mL absolute ethyl alcohols
It is uniformly dispersed into dispersion liquid；
3) by step 2) dispersion liquid be added to step 1) viscous fluid in, and add 10g
Oxiracetam be uniformly dispersed, then stand slough bubble；
4) viscous fluid after bubble will be removed to be coated with medicine film coating dryer, coating speed is
70cm/min, then with 85-88 DEG C of drying, stripping is obtained final product.
Embodiment 15
The preparation of Oxiracetam orodispersible film, using following steps：
1) by the filmogen of 50g (maltodextrin, sodium alginate and PVP-vinyl acetate,
Wherein sodium alginate consumption is 8g, and PVP-vinyl acetate consumption is 16g) it is anhydrous with 50mL
Ethanol dissolves, and sloughs bubble and uniform viscous fluid is obtained；
2) 18g glyceryl triacetates, 24g pregelatinized starch are disperseed with 50mL absolute ethyl alcohols
Non-uniform components dispersion liquid；
3) by step 2) dispersion liquid be added to step 1) viscous fluid in, and add 12g
Oxiracetam be uniformly dispersed, then stand slough bubble；
4) viscous fluid after bubble will be removed to be coated with medicine film coating dryer, coating speed is
70cm/min, then with 83-85 DEG C of drying, stripping is obtained final product.
Embodiment 16
The preparation of Oxiracetam orodispersible film, using following steps：
1) by the filmogen of 45g (maltodextrin, amylopectin and sodium alginate composition, its
Middle amylopectin consumption is 12g, and sodium alginate consumption is 3g) 50mL anhydrous alcohol solutions are used,
Slough bubble and uniform viscous fluid is obtained；
2) it is 15g glyceryl triacetates, 25g Ac-Di-Sols is anhydrous with 30mL
Ethanol is uniformly dispersed into dispersion liquid；
3) by step 2) dispersion liquid be added to step 1) viscous fluid in, and add 15g
Oxiracetam be uniformly dispersed, then stand slough bubble；
4) viscous fluid after bubble will be removed to be coated with medicine film coating dryer, coating speed is
65cm/min, then with 75-77 DEG C of drying, stripping is obtained final product.
Embodiment 17
The preparation of Oxiracetam orodispersible film, using following steps：
1) by the filmogen of 60g (maltodextrin, amylopectin and sodium alginate composition, its
Middle amylopectin consumption is 15g, and sodium alginate consumption is 10g) 70mL anhydrous alcohol solutions are used,
Slough bubble and uniform viscous fluid is obtained；
2) 20g glycerine, 10g pregelatinized starch 30mL absolute ethyl alcohols are uniformly dispersed composition
Dispersion liquid；
3) by step 2) dispersion liquid be added to step 1) viscous fluid in, and add 10g
Oxiracetam be uniformly dispersed, then stand slough bubble；
4) viscous fluid after bubble will be removed to be coated with medicine film coating dryer, coating speed is
80cm/min, then with 83-85 DEG C of drying, stripping is obtained final product.
Embodiment 18
The preparation of Oxiracetam orodispersible film, using following steps：
1) by the filmogen of 50g (maltodextrin, amylopectin and sodium alginate composition, its
Middle amylopectin consumption is 13g, and sodium alginate consumption is 7g) 55mL anhydrous alcohol solutions are used,
Slough bubble and uniform viscous fluid is obtained；
2) 15g glycerine, 20g Ac-Di-Sols are disperseed with 45mL absolute ethyl alcohols
Non-uniform components dispersion liquid；
3) by step 2) dispersion liquid be added to step 1) viscous fluid in, and add 15g
Oxiracetam be uniformly dispersed, then stand slough bubble；
4) viscous fluid after bubble will be removed to be coated with medicine film coating dryer, coating speed is
70cm/min, then with 75-78 DEG C of drying, stripping is obtained final product.
Embodiment 19
The preparation of Oxiracetam orodispersible film, using following steps：
1) by the maltodextrin of 50g 55mL anhydrous alcohol solutions, slough bubble and be obtained
Even viscous fluid；
2) 15g glycerine, 20g Ac-Di-Sols are disperseed with 45mL absolute ethyl alcohols
Non-uniform components dispersion liquid；
3) by step 2) dispersion liquid be added to step 1) viscous fluid in, and add 15g
Oxiracetam be uniformly dispersed, then stand slough bubble；
4) viscous fluid after bubble will be removed to be coated with medicine film coating dryer, coating speed is
70cm/min, then with 75-78 DEG C of drying, stripping is obtained final product.
Embodiment 20
The preparation of Oxiracetam orodispersible film, using following steps：
1) by the filmogen of 50g (hydroxypropyl cellulose, amylopectin and sodium alginate composition,
Wherein hydroxypropyl cellulose 30g, amylopectin consumption is 13g, and sodium alginate consumption is 7g)
55mL anhydrous alcohol solutions are used, bubble is sloughed and uniform viscous fluid is obtained；
2) 15g glycerine, 20g Ac-Di-Sols are disperseed with 45mL absolute ethyl alcohols
Non-uniform components dispersion liquid；
3) by step 2) dispersion liquid be added to step 1) viscous fluid in, and add 15g
Oxiracetam be uniformly dispersed, then stand slough bubble；
4) viscous fluid after bubble will be removed to be coated with medicine film coating dryer, coating speed is
70cm/min, then with 75-78 DEG C of drying, stripping is obtained final product.
Embodiment 21
The preparation of Oxiracetam orodispersible film, using following steps：
1) by the filmogen of 50g (maltodextrin, amylopectin and sodium alginate composition, its
Middle amylopectin consumption is 13g, and sodium alginate consumption is 7g) 55mL anhydrous alcohol solutions are used,
Slough bubble and uniform viscous fluid is obtained；
2) 15g glycerine, 20g Ac-Di-Sols are disperseed with 45mL absolute ethyl alcohols
Non-uniform components dispersion liquid；
3) by step 2) dispersion liquid be added to step 1) viscous fluid in, and add 15g
Oxiracetam be uniformly dispersed, then stand slough bubble；
4) viscous fluid after bubble will be removed to be coated with medicine film coating dryer, coating speed is
20cm/min, then with 75-78 DEG C of drying, stripping is obtained final product.
Embodiment 22
The preparation of Oxiracetam orodispersible film, using following steps：
1) by the filmogen of 50g (hydroxypropyl cellulose, amylopectin and sodium alginate composition,
Wherein hydroxypropyl cellulose 30g, amylopectin consumption is 13g, and sodium alginate consumption is 7g)
55mL anhydrous alcohol solutions are used, bubble is sloughed and uniform viscous fluid is obtained；
2) 15g glycerine, 20g Ac-Di-Sols are disperseed with 45mL absolute ethyl alcohols
Non-uniform components dispersion liquid；
3) by step 2) dispersion liquid be added to step 1) viscous fluid in, and add 15g
Oxiracetam be uniformly dispersed, then stand slough bubble；
4) viscous fluid after bubble will be removed to be coated with medicine film coating dryer, coating speed is
70cm/min, then with 50 DEG C of dryings, stripping is obtained final product.
Embodiment 23
Oxiracetam orodispersible film obtained in embodiment 1-22 is evaluated, including it is outer
Sight, thickness, ifs vitro disintegration, the evaluation of mechanical properties.
Evaluation method
Ocular estimate：Whether observation membrane surface is complete bright and clean, and whether thickness is consistent, and color and luster is
It is no it is uniform, whether there is obvious bubble.
Thickness measurement：Use resolution ratio carries out thickness for the digimatic micrometer of 0.001mm to film
Degree measurement, is determined 3 times respectively in every piece of the 3 of film different parts, and record data is obtained
Average thickness.
Ifs vitro disintegration time study：The disintegrating property of film is investigated by the disintegration time for determining film
And solvability.Magnetic stirring apparatus is placed in the beaker that 50mL distilled water is added 100mL
On, be clipped in for test film water-bath be put on clip by 37 DEG C of waters bath with thermostatic control, rotating speed 100r/min
Middle beginning timing, the time of record film dissolving.In this experiment, every piece of film is cut out at random
3 block sizes are cut for 1 × 1cm2Membranelle determine, using three average values of measurement result as survey
Amount result.
Mechanical performance is evaluated：
This experiment has used the universal testing machine of model 3365 to carry out the mechanical performance of film
Evaluate.It is 2 × 0.5cm by size2Film be put between two clips at a distance of 5cm.
Draw vice is with the speed membrane of 10mm/min.The elastic modelling quantity (EM) of film, refers to become in elasticity
In the shape stage, the ratio of applied stress and adaptability to changes, it is possible to use formula below is calculated：
Elastic modelling quantity=applied stress/adaptability to changes/area of section.
The tensile strength (TS) of film is also strength degree, refers to that material bears maximum before breaking
Stress value, computing formula is：
Tensile strength=applied stress/cross-sectional area.
The percent elongation (E%) of film is calculated by following formula：
Percent elongation=length incrementss/the original length × 100.
The Oxiracetam orodispersible film the performance test results such as following table of embodiment 1-7：
Note：1)The n=10 of the n=6 of thickness, quality and mechanical performance, content and uniformity of dosage units
Experiment display, the Oxiracetam orodispersible membrane surface prepared by embodiment 1-7 above
Smooth, thickness evenness preferably, possesses suitable suppleness and tensile property, conveniently stripped,
Disintegration time in 20s or so, no more than 22s.
The test result of the Oxiracetam orodispersible film of embodiment 8-15 is as follows：
Note：1)The n=10 of the n=6 of thickness, quality and mechanical performance, content and uniformity of dosage units
Experiment display, the Oxiracetam orodispersible film table prepared by embodiment 8-15 above
Face is smooth, and thickness evenness preferably, possesses suitable suppleness and tensile property, conveniently stripped,
Disintegration time in 20s or so, no more than 22s.
The test result of the Oxiracetam orodispersible film of embodiment 16-22 is as follows：
Note：1)The n=10 of the n=6 of thickness, quality and mechanical performance, content and uniformity of dosage units
Experiment display, the Oxiracetam orodispersible film table prepared by embodiment 16-18 above
Face is smooth, and thickness evenness preferably, possesses suitable suppleness and tensile property, conveniently stripped,
Disintegration time in 20s or so, no more than 22s；The membrane surface of embodiment 19 has projection,
The demoulding is also more difficult, and disintegration time limited also relative extension；The surface of embodiment 20 is smooth,
Toughness is preferable, the also easy demoulding, but disintegration time is slightly long；The membrane surface of embodiment 21
There is projection, the demoulding is also more difficult, and disintegration time limited also relative extension；Embodiment 22
Film is partially wet, there is adhesion phenomenon, and disintegration time is slightly long.
Oxiracetam orodispersible film obtained in embodiment 1-22 is carried out into dissolution in vitro examination
Test, as a result show：The Oxiracetam orodispersible film of embodiment 1-18 is opened in 10s
Begin to be disintegrated, drug release is rapid, and dissolution is complete more than the basic dissolutions of 90%, 10min in 5min；
Start disintegration in Oxiracetam orodispersible film 10s obtained in embodiment 19-22, release
Medicine is more rapid, in 5min dissolution more than dissolution in 70%, 10min more than 90%, 20min
Basic dissolution is complete；
Embodiment 19 and embodiment 20 have investigated filmogen to influence of the invention, alone
Maltodextrin is used as filmogen, and disintegration time is slightly long, there is the slightly poor situation of film forming,
Demoulding difficulty (embodiment 19) can be caused；Prepared by without maltodextrin film, film forming
Better performances, the easy demoulding, but disintegration time is (embodiment 20) more long.Embodiment 21
The influence of coating speed and drying temperature to film in film-forming process has been investigated with embodiment 22,
Wherein coating speed is too fast can cause partially wet, there is adhesion phenomenon；Coating speed can cause film slowly excessively
Agent overdrying, so that film is more crisp.Drying temperature can equally influence the brittleness and humidity of film.
To sum up, Oxiracetam orodispersible film appearance uniform of the present invention is complete, uniform color,
Thickness is consistent, physics and stable chemical nature, and disintegration time is short, and dissolution rate is fast, works fast
Speed.
Claims (7)
1. a kind of Oxiracetam orodispersible film, is obtained by the raw material including the Oxiracetam including 4-22 parts, 42-76 parts of filmogen, 10-38 parts of filler and 8-36 parts of plasticizer；The filmogen is comprising maltodextrin and at least another macromolecule filming material；Another macromolecule filming material is selected from hydroxypropyl cellulose, amylopectin, sodium alginate, pulullan polysaccharide, PVP-vinyl acetate or sodium carboxymethylcellulose；The plasticizer is selected from the one or more combination in glycerine, propane diols, glyceryl triacetate, triethyl citrate, dibutyl phthalate, PEG400 and PEG600；The filler is selected from the one or more combination in microcrystalline cellulose, low-substituted hydroxypropyl cellulose, pregelatinized starch, Ac-Di-Sol.
2. film as claimed in claim 1, it is characterised in that：It is obtained by the raw material including the Oxiracetam including 8-20 parts, 45-70 parts of filmogen, 15-32 parts of filler and 10-33 parts of plasticizer；The filmogen is comprising maltodextrin and at least another macromolecule filming material；Another macromolecule filming material is selected from hydroxypropyl cellulose, amylopectin, sodium alginate, pulullan polysaccharide, PVP-vinyl acetate or sodium carboxymethylcellulose, and the consumption of wherein hydroxypropyl cellulose, amylopectin, sodium alginate, pulullan polysaccharide, PVP-vinyl acetate or sodium carboxymethylcellulose is respectively：5 parts~40 parts, 10~15 parts, 3~15 parts, 1~5 part, 12~18 parts, 5~18 parts.
3. film as claimed in claim 1 or 2, it is characterised in that：It is obtained by the raw material including the Oxiracetam including 8-20 parts, 45-65 parts of filmogen, 15-30 parts of filler and 15-25 parts of plasticizer；The filmogen is that maltodextrin and hydroxypropyl cellulose are combined, and wherein hydroxypropyl cellulose consumption is 10 parts~30 parts；The filler is microcrystalline cellulose or low-substituted hydroxypropyl cellulose；The plasticizer is the one kind in glycerine, propane diols or triethyl citrate.
4. film as claimed in claim 1 or 2, it is characterised in that：It is obtained by the raw material including the Oxiracetam including 8-18 parts, 45-60 parts of filmogen, 15-25 parts of filler and 10-25 parts of plasticizer；The filmogen is that maltodextrin and amylopectin are constituted, and wherein amylopectin consumption is 11 parts~15 parts；The filler is low-substituted hydroxypropyl cellulose or pregelatinized starch；The plasticizer is propane diols or dibutyl phthalate.
5. the preparation method of Oxiracetam orodispersible film described in claim 1 or 2, using following steps：
1）By 40-70 parts of filmogen anhydrous alcohol solution, slough bubble and uniform viscous fluid is obtained；
2）10-33 parts of plasticizer, 15-32 parts of filler absolute ethyl alcohol are uniformly dispersed into dispersion liquid；
3）By step 2）Dispersion liquid be added to step 1）Viscous fluid in, and add 8-20 parts of Oxiracetam to be uniformly dispersed, then stand and slough bubble；
4）The viscous fluid medicine film coating dryer coating after bubble, dry, stripping will be removed to obtain final product.
6. a kind of preparation method of Oxiracetam orodispersible film, using following steps：
1) by 45-65 parts of filmogen anhydrous alcohol solution, slough bubble and uniform viscous fluid is obtained, the filmogen is that maltodextrin and hydroxypropyl cellulose are constituted, and wherein hydroxypropyl cellulose consumption is 10 parts~30 parts；
2）15-25 parts of plasticizer, 15-30 parts of filler absolute ethyl alcohol are uniformly dispersed into dispersion liquid, the plasticizer is glycerine, propane diols or triethyl citrate, and the filler is microcrystalline cellulose or low-substituted hydroxypropyl cellulose；
3）By step 2）Dispersion liquid be added to step 1）Viscous fluid in, and add 8-20 parts of Oxiracetam to be uniformly dispersed, then stand and slough bubble；
4）The viscous fluid after bubble will be removed to be coated with medicine film coating dryer, coating speed is 60-85cm/min, and then with 70-90 DEG C of drying, stripping is obtained final product.
7. a kind of preparation method of Oxiracetam orodispersible film, using following steps：
1) by 45-60 parts of filmogen anhydrous alcohol solution, slough bubble and uniform viscous fluid is obtained, the filmogen is that maltodextrin and amylopectin are combined, and wherein amylopectin consumption is 11 parts~15 parts；
2）10-25 parts of plasticizer, 15-25 parts of filler absolute ethyl alcohol are uniformly dispersed into dispersion liquid, the plasticizer is propane diols or dibutyl phthalate, and the filler is low-substituted hydroxypropyl cellulose or pregelatinized starch；
3）By step 2）Dispersion liquid be added to step 1）Viscous fluid in, and add 8-18 parts of Oxiracetam to be uniformly dispersed, then stand and slough bubble；
4）The viscous fluid after bubble will be removed to be coated with medicine film coating dryer, coating speed is 60-80cm/min, and then with 70-85 DEG C of drying, stripping is obtained final product.
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Application publication date: 20170613 |