JP2021508316A - サフィナミドを含む医薬組成物 - Google Patents
サフィナミドを含む医薬組成物 Download PDFInfo
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- JP2021508316A JP2021508316A JP2020524227A JP2020524227A JP2021508316A JP 2021508316 A JP2021508316 A JP 2021508316A JP 2020524227 A JP2020524227 A JP 2020524227A JP 2020524227 A JP2020524227 A JP 2020524227A JP 2021508316 A JP2021508316 A JP 2021508316A
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- particles
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- saffinamide
- taste masking
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- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 235000019888 Vivapur Nutrition 0.000 description 1
- 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 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000011149 active material Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 239000000010 aprotic solvent Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 235000019606 astringent taste Nutrition 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 229960004365 benzoic acid Drugs 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 239000000378 calcium silicate Substances 0.000 description 1
- 229910052918 calcium silicate Inorganic materials 0.000 description 1
- 229960003340 calcium silicate Drugs 0.000 description 1
- 235000012241 calcium silicate Nutrition 0.000 description 1
- OYACROKNLOSFPA-UHFFFAOYSA-N calcium;dioxido(oxo)silane Chemical compound [Ca+2].[O-][Si]([O-])=O OYACROKNLOSFPA-UHFFFAOYSA-N 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 229960004106 citric acid Drugs 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 239000008119 colloidal silica Substances 0.000 description 1
- 239000000084 colloidal system Substances 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000010485 coping Effects 0.000 description 1
- 229960001681 croscarmellose sodium Drugs 0.000 description 1
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 1
- 150000004683 dihydrates Chemical class 0.000 description 1
- FSBVERYRVPGNGG-UHFFFAOYSA-N dimagnesium dioxido-bis[[oxido(oxo)silyl]oxy]silane hydrate Chemical compound O.[Mg+2].[Mg+2].[O-][Si](=O)O[Si]([O-])([O-])O[Si]([O-])=O FSBVERYRVPGNGG-UHFFFAOYSA-N 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 229960003638 dopamine Drugs 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 210000003238 esophagus Anatomy 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 210000000887 face Anatomy 0.000 description 1
- 239000007888 film coating Substances 0.000 description 1
- 238000009501 film coating Methods 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 210000004051 gastric juice Anatomy 0.000 description 1
- 210000004704 glottis Anatomy 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 229960001680 ibuprofen Drugs 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 239000008384 inner phase Substances 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 229960001375 lactose Drugs 0.000 description 1
- 210000000867 larynx Anatomy 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000002932 luster Substances 0.000 description 1
- 239000000391 magnesium silicate Substances 0.000 description 1
- 229940099273 magnesium trisilicate Drugs 0.000 description 1
- 229910000386 magnesium trisilicate Inorganic materials 0.000 description 1
- 235000019793 magnesium trisilicate Nutrition 0.000 description 1
- 229960002510 mandelic acid Drugs 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 229920003145 methacrylic acid copolymer Polymers 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-M methanesulfonate group Chemical group CS(=O)(=O)[O-] AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 1
- 239000011859 microparticle Substances 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 150000004682 monohydrates Chemical class 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 210000001577 neostriatum Anatomy 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000007935 oral tablet Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000008385 outer phase Substances 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 238000003921 particle size analysis Methods 0.000 description 1
- 239000011049 pearl Substances 0.000 description 1
- 238000005453 pelletization Methods 0.000 description 1
- 230000008447 perception Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229920002959 polymer blend Polymers 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 230000021317 sensory perception Effects 0.000 description 1
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
- 229960004029 silicic acid Drugs 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
- 239000004299 sodium benzoate Substances 0.000 description 1
- 235000010234 sodium benzoate Nutrition 0.000 description 1
- 230000003381 solubilizing effect Effects 0.000 description 1
- 229960002920 sorbitol Drugs 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 229960004793 sucrose Drugs 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000007916 tablet composition Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 229960001367 tartaric acid Drugs 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 210000001779 taste bud Anatomy 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 239000011882 ultra-fine particle Substances 0.000 description 1
- 239000004565 water dispersible tablet Substances 0.000 description 1
- 229920003176 water-insoluble polymer Polymers 0.000 description 1
- 238000005550 wet granulation Methods 0.000 description 1
Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5073—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals having two or more different coatings optionally including drug-containing subcoatings
- A61K9/5078—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals having two or more different coatings optionally including drug-containing subcoatings with drug-free core
-
- 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
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin
-
- 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
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
- A61K9/2077—Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
- A61K9/2081—Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets with microcapsules or coated microparticles according to A61K9/50
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Zoology (AREA)
- Nutrition Science (AREA)
- Physiology (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
【選択図】なし
Description
a.サフィナミド又はその薬学的に許容される塩を含むコア
b.前記コア上にコーティングを形成する味覚マスキングポリマー組成物
を含み、前記コアは、結合剤の存在下で、前記サフィナミド又はその薬学的に許容される塩により積層された不活性粒子を含む。
a.不活性粒子上に活性医薬成分を積層してコアを得る工程と、
b.味覚マスキングポリマー組成物により前記コアをコーティングする工程。
a.流動床(トップスプレー式添加):
連続的に撹拌しながら30℃で水に結合剤賦形剤を添加し、可溶化終了後、サフィナミドメタンスルホン酸塩、次に凝集防止剤賦形剤を添加することにより、結合溶液を調製した。
コア1
サフィナミドメタンスルホン酸塩 68.6%
MCC100 25.0%
PVP K30 4.3%
タルク 2.1%
コア2
サフィナミドメタンスルホン酸塩 70.1%
MCC100 24.0%
α化デンプン RX 1500 3.8%
タルク 2.1%
コア3
サフィナミドメタンスルホン酸塩 69.2%
MCC100 24.0%
PEG 6000 4.5%
タルク 2.3%
コア4
サフィナミドメタンスルホン酸塩 68.7%
MCC100 24.8%
PVP K90 4.3%
タルク 2.2%
コア5
サフィナミドメタンスルホン酸塩 70.9%
MCC100 23.0%
ヒドロキシプロピルメチルセルロース 4.0%
タルク 2.1%
コア6
サフィナミドメタンスルホン酸塩 69.5%
MCC100 24.1%
PEG 6000 4.4%
タルク 2.0%
a.流動床(ローター):
連続的に撹拌しながら室温で水に結合剤賦形剤を添加し、完全に可溶化させることにより、結合溶液を調製した。不活性粒子を流動床(GXR−35ローターインサートを備えたVFC−LAB3、Freund Vactor社製)に置き、350rpmで駆動させ、室温でそれを維持した。サフィナミドメタンスルホン酸塩をK−tron圧気粉体供給システムに投入し、約25g/分の流速で流動床に添加し、同時に、約15g/分の流速で結合溶液を噴霧し、工程終了後、得られたコアを約30分間60℃で乾燥させた。造粒工程終了後、生成物を吐出させ、篩分けを行い、200〜450μmの範囲の粒度のフラクションを回収した。上記の手順を用い、以下の組成のコアを調製した。
コア10
サフィナミドメタンスルホン酸塩 67.2%
MCC100 26.0%
PEG6000 4.8%
タルク 2.0%
コア11
サフィナミドメタンスルホン酸塩 68.0%
MCC100 2.0%
PVP K30 4.3%
タルク2.7%
コア12
サフィナミドメタンスルホン酸塩 67.8%
MCC100 24.9%
デンプン RX1500 5.2%
タルク 2.1%
a.ポリマーコーティング組成物:pH依存的
実施例1及び2の教示に従い調製したサフィナミドメタンスルホン酸塩のコアを流動層システム(GPCG 1.1)に投入し、Eudragit(登録商標)EPO及び機能性賦形剤の懸濁液によりコーティングした。コーティング工程は、コアの温度を約30〜35℃に維持しつつ、4〜5ml/分の噴霧速度及び2.0barの噴霧圧により行った。堆積工程終了後、粒子を流動床内部で45〜50℃で約30分間乾燥させた。
実施例1及び2の教示に従い調製したサフィナミドメタンスルホン酸塩のコアを流動層システム(GPCG 1.1)に投入し、エチルセルロース/ヒドロキシプロピルメチルセルロース(Clear/Methocel(登録商標)E5)の懸濁液によりコーティングした。コーティング工程は、造粒物の温度を約44〜48℃に維持しつつ、7〜10ml/分の噴霧速度及び2.0barの噴霧圧により行った。堆積工程終了後、造粒物を流動床内部で45〜50℃で約30分間乾燥させた。
実施例3に記載の手順の後、以下の組成を有する本発明の粒子を調製した。
粒子1
コア1 52.5%
Eudragit(登録商標) EPO 31.5%
ドデシル硫酸ナトリウム 2.5%
ステアリン酸 3.5%
タルク 10.0%
粒子2
コア1 68.40%
Surelease(登録商標)クリア 26.90%
Methocel(登録商標)E5 4.70%
粒子3
コア1 63.90%
Surelease(登録商標)クリア 27.30%
Methocel(登録商標)E5 4.80%
TEC 4.00%
粒子4
コア5 63.70%
Surelease(登録商標)クリア 22.50%
Methocel(登録商標)E5 9.70%
TEC 4.10%
粒子5
コア11 66.20%
Surelease(登録商標)クリア 25.10%
Methocel(登録商標)E5 4.40%
PEG 6000 4.30%
粒子6
コア1 80.00%
Surelease(登録商標)クリア 12.40%
Methocel(登録商標)E5 5.30%
TEC 2.30%
粒子7
コア11 80.10%
Surelease(登録商標)クリア 15.00%
Methocel(登録商標)E5 2.70%
TEC 2.20%
粒子8
コア4 81.60%
Surelease(登録商標)クリア 15.60%
Methocel(登録商標)E5 2.80%
実施例5に記載の手順の後、以下の組成を有する口腔内崩壊錠剤を調製した。
錠剤1
粒子2 57.60%
マンニトール 21.80%
デンプン 4.40%
PEG 6000 3.70%
クロスポビドン 10.00%
ステアリン酸マグネシウム 2.50%
錠剤2
粒子3 56.00%
マンニトール 23.50%
デンプン 4.80%
PEG 6000 3.20%
クロスポビドン 10.00%
ステアリン酸マグネシウム 2.50%
錠剤3
粒子5 58.60%
マンニトール 20.00%
デンプン 4.30%
PEG 6000 3.80%
クロスポビドン 10.00%
ステアリン酸マグネシウム 2.50%
錠剤4
粒子8 53.80%
マンニトール 25.10%
デンプン 5.10%
PEG 6000 4.00%
クロスポビドン 9.60%
ステアリン酸マグネシウム 2.40%
実施例7に記載の手順の後、以下の組成物を有するサシェを調製した。
口腔内分散性紛体1
粒子1 36.6%
マンニトール 38.0%
炭酸カルシウム 25.4%
口腔内分散性紛体2
粒子4 29.2%
マンニトール 42.5%
炭酸カルシウム 28.3%
口腔内分散性紛体3
粒子5 29.3%
マンニトール 42.4%
炭酸カルシウム 28.3%
活性医薬成分であるサフィナミドメタンスルホン酸の不快な味覚及び刺激感を評価するため、100mgのサフィナミド塩基と当量の、サフィナミドメタンスルホン酸を用いたインビボ試験を実施した。
活性医薬成分(サフィナミドメタンスルホン酸塩)の味覚マスキングを評価するため、実施例6に記載される教示に従い調製した口腔内崩壊錠剤を用いた試験をインビボで実施した。
1=不快な味覚も刺激感もない
2=苦みのノート及び若干の知覚可能な刺激あり
3=苦み及び明らかに知覚可能な刺激あり
4=苦み及び非常に強い刺激あり
5=極度の苦み及び耐え難い刺激あり
活性医薬成分(サフィナミドメタンスルホン酸塩)の味覚マスキングを評価するため、実施例8に記載の教示に従い調製した口腔内分散性粉末を用いた試験をインビボで実施した。
1=不快な味覚も刺激感もない
2=苦みのノート及び若干の知覚可能な刺激あり
3=苦み及び明らかに知覚可能な刺激あり
4=苦み及び非常に強い刺激あり
5=極度の苦み及び耐え難い刺激あり
引用文献の中国特許出願公開第104546747号の実施例5及び6の教示に従い調製した口腔内崩壊錠剤を用いて比較試験をインビボで実施した。
引用文献の中国特許出願第104546747の実施例5の教示に従い調製した口腔内崩壊錠剤の味覚マスキング特性を、pH約6.8の人工唾液における前記剤形の溶解性を試験した際の有効成分の放出(%)を測定することにより評価した。該試験では、服用後1分以内の10%以下の放出を良好であると考えるものである。
Claims (15)
- a.サフィナミド又はその薬学的に許容される塩を含むコア
b.前記コアの上にコーティングされた味覚マスキングポリマー組成物
を各々含み、
前記コアが、結合剤の存在下で前記サフィナミド又はその薬学的に許容される塩により積層された不活性粒子を含む、複数の粒子。 - 前記粒子が500μm以下の粒子サイズを有する、請求項1に記載の複数の粒子。
- 前記コアがサフィナミドメタンスルホン酸塩を含む、請求項1又は2に記載の複数の粒子。
- 前記結合剤が、ポビドン(PVP)、ポリエチレングリコール(PEG)、α化デンプン、ヒドロキシプロピルメチルセルロース(HPMC)、微結晶性セルロース及びそれらの混合物から選択される、請求項1に記載の複数の粒子。
- 前記不活性粒子が微結晶性セルロースの粒子である、請求項1に記載の複数の粒子。
- 前記味覚マスキングポリマー組成物が、10〜70%の量で存在する、請求項1に記載の複数の粒子。
- 前記味覚マスキングポリマー組成物が、20〜40%の量で存在する、請求項6に記載の複数の粒子。
- 前記味覚マスキングポリマー組成物が、不溶性及び水溶性のセルロース系ポリマーの混合物を含む、請求項1に記載の複数の粒子。
- 前記味覚マスキングポリマー組成物が可塑剤を含む、請求項1に記載の複数の粒子。
- 前記可塑剤が少なくとも2%の量で存在する、請求項9に記載の複数の粒子。
- a.医薬有効成分を不活性粒子に積層させてコアを形成することと、
b.味覚マスキングポリマー組成物により前記コアをコーティングすることと、
を含む、請求項1に記載の複数の粒子の調製方法。 - 結合剤の存在下で、水性ビヒクル中に前記医薬有効成分を溶解させるか、又は分散させることを更に含む、請求項11に記載の方法。
- 請求項1に記載の複数の粒子を含む、口腔内崩壊錠剤。
- 経口投与製剤の調製における、請求項1に記載の複数の粒子の使用。
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