CN1154476C - 改进的迅速崩解片剂 - Google Patents
改进的迅速崩解片剂 Download PDFInfo
- Publication number
- CN1154476C CN1154476C CNB998138010A CN99813801A CN1154476C CN 1154476 C CN1154476 C CN 1154476C CN B998138010 A CNB998138010 A CN B998138010A CN 99813801 A CN99813801 A CN 99813801A CN 1154476 C CN1154476 C CN 1154476C
- Authority
- CN
- China
- Prior art keywords
- tablet
- weight
- ratio
- agent
- polyhydric alcohol
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 31
- 239000000203 mixture Substances 0.000 claims abstract description 30
- 239000002245 particle Substances 0.000 claims abstract description 10
- 239000000314 lubricant Substances 0.000 claims abstract description 9
- 210000003296 saliva Anatomy 0.000 claims abstract description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical group O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 25
- 150000005846 sugar alcohols Polymers 0.000 claims description 17
- 239000011248 coating agent Substances 0.000 claims description 13
- 238000000576 coating method Methods 0.000 claims description 13
- 239000003085 diluting agent Substances 0.000 claims description 13
- 239000000843 powder Substances 0.000 claims description 13
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 12
- 239000000377 silicon dioxide Substances 0.000 claims description 12
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 claims description 11
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims description 11
- 229930195725 Mannitol Natural products 0.000 claims description 11
- 239000000594 mannitol Substances 0.000 claims description 11
- 235000010355 mannitol Nutrition 0.000 claims description 11
- 230000000149 penetrating effect Effects 0.000 claims description 9
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 claims description 8
- 229960001680 ibuprofen Drugs 0.000 claims description 8
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 claims description 7
- 239000000600 sorbitol Substances 0.000 claims description 7
- 235000010356 sorbitol Nutrition 0.000 claims description 7
- WBZFUFAFFUEMEI-UHFFFAOYSA-M Acesulfame k Chemical compound [K+].CC1=CC(=O)[N-]S(=O)(=O)O1 WBZFUFAFFUEMEI-UHFFFAOYSA-M 0.000 claims description 6
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical group CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 claims description 6
- 235000010358 acesulfame potassium Nutrition 0.000 claims description 6
- 229960004998 acesulfame potassium Drugs 0.000 claims description 6
- 239000000619 acesulfame-K Substances 0.000 claims description 6
- 229960001138 acetylsalicylic acid Drugs 0.000 claims description 6
- 239000008187 granular material Substances 0.000 claims description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical group [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 6
- 229960005489 paracetamol Drugs 0.000 claims description 6
- -1 polyethylene pyrrolidone Polymers 0.000 claims description 6
- 239000004480 active ingredient Substances 0.000 claims description 5
- 239000003086 colorant Substances 0.000 claims description 5
- 238000004132 cross linking Methods 0.000 claims description 5
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 4
- 238000005056 compaction Methods 0.000 claims description 4
- 210000000214 mouth Anatomy 0.000 claims description 4
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 claims description 3
- 108010011485 Aspartame Proteins 0.000 claims description 3
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 claims description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 3
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 claims description 3
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 claims description 3
- 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 3
- 239000000605 aspartame Substances 0.000 claims description 3
- 235000010357 aspartame Nutrition 0.000 claims description 3
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical group OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 claims description 3
- 229960003438 aspartame Drugs 0.000 claims description 3
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 claims description 3
- 125000004432 carbon atom Chemical group C* 0.000 claims description 3
- 235000019359 magnesium stearate Nutrition 0.000 claims description 3
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 claims description 3
- 235000012239 silicon dioxide Nutrition 0.000 claims description 3
- 239000000811 xylitol Substances 0.000 claims description 3
- 235000010447 xylitol Nutrition 0.000 claims description 3
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 claims description 3
- 229960002675 xylitol Drugs 0.000 claims description 3
- FTLYMKDSHNWQKD-UHFFFAOYSA-N (2,4,5-trichlorophenyl)boronic acid Chemical compound OB(O)C1=CC(Cl)=C(Cl)C=C1Cl FTLYMKDSHNWQKD-UHFFFAOYSA-N 0.000 claims description 2
- 239000001329 FEMA 3811 Substances 0.000 claims description 2
- 239000005913 Maltodextrin Substances 0.000 claims description 2
- 229920002774 Maltodextrin Polymers 0.000 claims description 2
- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims description 2
- 235000021355 Stearic acid Nutrition 0.000 claims description 2
- 239000003125 aqueous solvent Substances 0.000 claims description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 2
- MVPICKVDHDWCJQ-UHFFFAOYSA-N ethyl 3-pyrrolidin-1-ylpropanoate Chemical compound CCOC(=O)CCN1CCCC1 MVPICKVDHDWCJQ-UHFFFAOYSA-N 0.000 claims description 2
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 claims description 2
- 229940035034 maltodextrin Drugs 0.000 claims description 2
- ITVGXXMINPYUHD-CUVHLRMHSA-N neohesperidin dihydrochalcone Chemical compound C1=C(O)C(OC)=CC=C1CCC(=O)C(C(=C1)O)=C(O)C=C1O[C@H]1[C@H](O[C@H]2[C@@H]([C@H](O)[C@@H](O)[C@H](C)O2)O)[C@@H](O)[C@H](O)[C@@H](CO)O1 ITVGXXMINPYUHD-CUVHLRMHSA-N 0.000 claims description 2
- 229940089953 neohesperidin dihydrochalcone Drugs 0.000 claims description 2
- 235000010434 neohesperidine DC Nutrition 0.000 claims description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 claims description 2
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 claims description 2
- 229940085605 saccharin sodium Drugs 0.000 claims description 2
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 claims description 2
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 claims description 2
- 229940045902 sodium stearyl fumarate Drugs 0.000 claims description 2
- 239000008117 stearic acid Substances 0.000 claims description 2
- 239000000796 flavoring agent Substances 0.000 abstract description 5
- 239000004150 EU approved colour Substances 0.000 abstract 1
- 239000000969 carrier Substances 0.000 abstract 1
- 230000006835 compression Effects 0.000 abstract 1
- 238000007906 compression Methods 0.000 abstract 1
- 238000007865 diluting Methods 0.000 abstract 1
- 235000003599 food sweetener Nutrition 0.000 abstract 1
- 229940006093 opthalmologic coloring agent diagnostic Drugs 0.000 abstract 1
- 239000008191 permeabilizing agent Substances 0.000 abstract 1
- 239000003765 sweetening agent Substances 0.000 abstract 1
- 239000003826 tablet Substances 0.000 description 42
- 235000013355 food flavoring agent Nutrition 0.000 description 4
- 241000432824 Asparagus densiflorus Species 0.000 description 3
- 239000001856 Ethyl cellulose Substances 0.000 description 3
- 125000002252 acyl group Chemical group 0.000 description 3
- 239000007931 coated granule Substances 0.000 description 3
- 229920001249 ethyl cellulose Polymers 0.000 description 3
- 235000019325 ethyl cellulose Nutrition 0.000 description 3
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 3
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 3
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 3
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 150000004702 methyl esters Chemical class 0.000 description 3
- 235000005979 Citrus limon Nutrition 0.000 description 2
- 244000131522 Citrus pyriformis Species 0.000 description 2
- 229920002785 Croscarmellose sodium Polymers 0.000 description 2
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 2
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 2
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 229940071826 hydroxyethyl cellulose Drugs 0.000 description 2
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 2
- DKXULEFCEORBJK-UHFFFAOYSA-N magnesium;octadecanoic acid Chemical compound [Mg].CCCCCCCCCCCCCCCCCC(O)=O DKXULEFCEORBJK-UHFFFAOYSA-N 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 235000019629 palatability Nutrition 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 244000246386 Mentha pulegium Species 0.000 description 1
- 235000016257 Mentha pulegium Nutrition 0.000 description 1
- 235000004357 Mentha x piperita Nutrition 0.000 description 1
- VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 description 1
- 240000001890 Ribes hudsonianum Species 0.000 description 1
- 235000016954 Ribes hudsonianum Nutrition 0.000 description 1
- 235000001466 Ribes nigrum Nutrition 0.000 description 1
- 229940063834 carboxymethylcellulose sodium Drugs 0.000 description 1
- 239000007910 chewable tablet Substances 0.000 description 1
- 229940068682 chewable tablet Drugs 0.000 description 1
- 239000008119 colloidal silica Substances 0.000 description 1
- 239000001767 crosslinked sodium carboxy methyl cellulose Substances 0.000 description 1
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 1
- 239000004148 curcumin Substances 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- HXTFUVWJFLDLJP-UHFFFAOYSA-N ethyl 2-[4-(2-methylpropyl)phenyl]propanoate Chemical group CCOC(=O)C(C)C1=CC=C(CC(C)C)C=C1 HXTFUVWJFLDLJP-UHFFFAOYSA-N 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 235000001050 hortel pimenta Nutrition 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- PNJWIWWMYCMZRO-UHFFFAOYSA-N pent‐4‐en‐2‐one Natural products CC(=O)CC=C PNJWIWWMYCMZRO-UHFFFAOYSA-N 0.000 description 1
- 229940093429 polyethylene glycol 6000 Drugs 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
- STFSJTPVIIDAQX-LTRPLHCISA-M sodium;(e)-4-octadecoxy-4-oxobut-2-enoate Chemical group [Na+].CCCCCCCCCCCCCCCCCCOC(=O)\C=C\C([O-])=O STFSJTPVIIDAQX-LTRPLHCISA-M 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000007916 tablet composition Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
-
- 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
- A61K9/2072—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
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Zoology (AREA)
- Physiology (AREA)
- Nutrition Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Detergent Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Saccharide Compounds (AREA)
- General Preparation And Processing Of Foods (AREA)
Abstract
本发明涉及改进的可以在口腔内在与唾液接触不到40秒的时间内崩解的多颗粒片剂，其特征在于该片剂是基于具有固有压制特性的包衣活性成分颗粒和赋形剂的混合物，赋形剂混合物与包衣活性成分颗粒的比例为0.4至6重量份，所述赋形剂的混合物含有崩解剂、具有粘合特性的可溶性稀释剂、润滑剂、渗透剂、有利地润滑剂、甜味剂、矫味剂和着色剂，崩解剂的比例为1至15%(重量)，可溶性试剂的比例为30至90%(重量)，均以片剂的重量计。
Description
技术领域
本发明涉及可迅速崩解的片剂，该片剂可在口腔内在不到40秒的时间内崩解，所述片剂含有具有固有压制特性的包衣活性成分颗拉和赋形剂混合物。
背景技术
作为可用于生产本发明片剂的活性成分，可以列举例如布洛芬、对乙酰氨基酚和阿司匹林。
基于布洛芬的片剂是已知的。
美国专利5,215,755描述了其中布洛芬以带有基于羟乙基纤维素或羟乙基纤维素/羟丙甲基纤维素混合物的包衣的颗粒形式存在的咀嚼片剂。选择该包衣是为了克服在仅用乙基纤维素的现有技术的包衣中所观察到的缺点。
发明内容
本发明的目的是提供利用包衣的活性成分颗粒制得的片剂，该片剂不仅可以在口腔内在不到40秒的时间内迅速崩解，而且还具有良好的适口性，此外，该片剂还具有令人满意的硬度特性以便进行工业生产，并且在常规的存放条件下能够保持得足够好以便于患者使用，而且这些片剂还可以使活性成分的生物利用度达到最佳。
本发明片剂的特征在于，该片剂是基于具有固有压制特性的包衣活性成分颗粒和赋形剂混合物，赋形剂混合物与包衣活性成分的比例为0.4至6重量份，优选1至4重量份，所述赋形剂的混合物含有：|
-崩解剂；
-具有粘合特性的可溶性稀释剂，其由少于13个碳原子的多元醇组成，并且可以是平均颗粒直径为100至500μm的可直接压制的产品形式或是平均颗粒直径小于100μm的粉末形式，该多元醇优选选自甘露糖醇、木糖醇、山梨糖醇和麦芽糖醇，应当理解，山梨醇不能单独使用，并且当仅有一种其有粘合特性的可溶性稀释剂时，其以可直接压制的产品的形式使用，而当有至少两种具有粘合特性的可溶性稀释剂时，一种以可直接压制的形式存在，另一种以粉末的形式存在，并且多元醇可以相同，可直接压制的多元醇与粉末多元醇的比例为99/1至20/80，优选80/20至20/80；
-润滑剂；
-渗透剂；和
一有利地甜味剂、矫味剂和着色剂，
崩解剂的比例为1至15％(重量)，优选2至7％(重量)，可溶性试剂的比例为30至90％(重量)，优选40至70％(重量)，均以片剂的重量计。
具有粘合特性的可溶性稀释剂由少于13个碳原子的多元醇组成，其可以是平均颗粒直径在100至500μm之间的可直接压制的产品形式，或是平均颗粒直径小于100μm的粉末形式，该多元醇优选选自甘露糖醇、木糖醇、山梨糖醇和麦芽糖醇，并且不能单独使用山梨糖醇。
如果仅有一种具有粘合特性的可溶性稀释剂，则该稀释剂不能是山梨糖醇，并且以可直接压制的产品的形式使用。
如果使用至少两种具有粘合特性的可溶性稀释剂，则一种以可直接压制的产品的形式存在，可由相同多元醇组成的另一种以组成颗粒的平均直径小于100μm的粉末形式存在，可直接压制的多元醇与粉末多元醇的比例为99/1至20/80，优选80/20至20/80。
崩解剂尤其是选自交联的羧甲基纤维素钠、交联聚乙烯基吡咯烷酮及其混合物。凭借对崩解剂及其比例的选择，当将片剂在密封的包装中放置在至少30℃的温度下时，该片剂保持在常规片剂操作条件下可接受的硬度。
用于构成赋形剂的崩解剂和可溶性试剂的比例分别为1至15％(重量)和30至90％(重量)，均以片剂的重量计。
优选用于该赋形剂混合物的润滑剂选自硬脂酸镁、十八烷基富马酸钠、硬脂酸、微粒化的聚氧乙烯二醇(微粒化的聚乙二醇6000)及其混合物。其可以以0.05至2％的比例使用，以片剂的总重量计。
作为渗透剂，使用尤其选自对含水溶剂具有高亲和性的二氧化硅，例如商标为Syloid的沉淀法二氧化硅、麦芽糖糊精、β-环糊精及其混合物。
渗透剂可以产生亲水性网状结构，该结构可以促进唾液的渗透从而促进片剂更充分地崩解。
在一个非常有利的本发明片剂的实施方案中，渗透剂是商标为SyloidFP244的沉淀法二氧化硅，事实上，该二氧化硅不仅可以促进片剂更充分地崩解，而且还可以通过它的助流剂特性在压片的过程中有助于颗粒的重排，因此，它一方面可以减少为了保证在最佳条件进行生产所需的疏水性润滑剂的用量，另一方面还可以降低生产可以在工业条件下操作的片剂所需的压力强度。
渗透剂的比例在0.5至5％之间，以片剂的重量计。
作为本发明片剂组合物的组成部分的赋形剂混合物中还可以含有甜味剂和任选的矫味剂以及着色剂。
甜味剂可以尤其选自天冬酰苯丙氨酸甲酯、丁磺氨钾、糖精钠、新橙皮苷双氢查耳酮及其混合物。
矫味剂和着色剂是制药业中常用于制备片剂的那些。
与现有的所述类型的片剂相比，本发明的片剂具有改善的适口性，特别是改善了的味道和结构，并且可以降低片剂重量与活性成分剂量的比例。
本发明的片剂具有令人满意的硬度，可以在常规的操作条件下处理而无需采取特殊的操作预防措施。例如，满足这些条件的硬度通常在20至70牛顿之间。
本发明的片剂可以通过如下方式或其它适宜的方法制备。将具有固有压制特性的包衣活性成分颗粒以上述比例加入到含有崩解剂、具有粘合特性的可溶性稀释剂、渗透剂和有利地润滑剂、甜味剂、矫味剂和着色剂的赋形剂的混合物中。将得到的混合物在于混合器内匀化，然后对其施加压力以使得到的片剂具有令人满意的硬度，这一硬度可以使其生产以工业规模进行并在常规的操作条件下处理而无需特殊的操作防护；例如，满足这些条件的硬度通常在20至70牛顿之间。
具体实施方式
实施例
实施例1：含有200mg布洛芬的片剂
表I给出了该片剂的单位配方和百分比配方。
表I
| 成分 | 单位配方 | 百分比配方 |
| 包衣的布洛芬颗粒粒状甘露糖醇粉状甘露糖醇交联羧甲基纤维素钠沉淀法二氧化硅天冬酰苯丙氨酸甲酯丁磺氨钾柠檬矫味剂薄荷矫味剂硬脂酸镁 | 261.70186.65186.6521.007.009.606.4016.002.003.00 | 37.2426.7126.763.001.001.370.912.290.290.43 |
| 700.00mg | 100.00 |
该片剂按照如下描述制备。
将表I所列的赋形剂用筛孔尺寸为1000μm的网过筛。
将不同的成分分别在适宜容量的容器中称重。
将包衣的布洛芬颗粒(具有下表II所给出的配方)、粒状甘露糖醇、粉状甘露糖醇、交联类甲基纤维素钠、天冬酰苯丙氨酸甲酯、丁磺氨钾、沉淀法二氧化硅和矫味剂加入到旋转搅拌器内。
制备均匀的混合物。
停止搅拌，加入硬脂酸镁并根据混合物的重量继续搅拌1至5分钟。
将得到的混合物在回转机械上压制成具有如下特性的片剂：
-平均重量在665mg至735mg之间；
一断裂强度在20至50N之间；
-在口腔内的平均崩解时间少于40秒。
该崩解时间相对于从片剂被置于口腔内与唾液接触到由于片剂与唾液接触而崩解所形成的悬浮液被吞咽的时间。
表II
包衣布洛芬颗粒的配方
| 布洛芬乙基纤维素沉淀法二氧化硅羟丙甲基纤维素 | 200.0040.0013.708.00 |
| 261.70mg |
实施例2：含有50Omg阿司匹林的片剂
表III给出了该片剂的单位配方和百分比配方
表III
| 成分包衣的阿司匹林颗粒粒状甘露糖醇粉状甘露糖醇交联聚乙烯基吡咯烷酮沉淀法二氧化硅天冬酰苯丙氨酸甲酯丁磺氨钾柠檬矫味剂十八烷基富马酸钠 | 单位配方564.00333.00333.00120.0014.0014.409.605.007.00 | 百分比配方40.2623.7723.778.571.001.030.690.360.50 |
| 1400.00mg | 99.928622 |
按照与实施例1相同的方式用具有下表IV所示配方的包衣颗粒制备片剂。
表IV
包衣阿司匹林颗粒的配方
| 阿司匹林乙基纤维素羟丙甲基纤维素胶态二氧化硅 | 500.050.010.04.00 |
| 564.0mg |
实施例3：含有500mg对乙酰氨基酚的片剂。
表V给出了该片剂的单位配方和百分比配方。
表V
| 成分 | 单位配方 | 百分比配方 |
| 包衣的对乙酰氨基酚颗粒粒状甘露糖醇粉状甘露糖醇交联聚乙烯基吡咯烷酮沉淀法二氧化硅天冬酰苯丙氨酸甲酯丁磺氨钾黑茶藨子矫味剂硬脂酸镁 | 566.50331.30331.30120.0014.0019.2012.805.000.90 | 40.4423.6523.658.571.001.370.910.360.06 |
| 1401.00mg | 100.00 |
按照与实施例1相同的方式用具有下表VI所示配方的包衣颗粒制备片剂。
表VI
包衣对乙酰氨基酚颗粒的配方
| 对乙酰氨基酚30％聚(丙烯酸乙酯/甲基丙烯酸甲酯)分散液氨基烷基甲基丙烯酸共聚物沉淀法二氧化硅 | 500.017.033.016.5 |
| 566.5mg |
Claims (12)
1.改进的多颗粒片剂，该片剂可以在口腔内在与唾液接触不到40秒的时间内崩解，其特征在于，该片剂是基于具有固有压制特性的包衣活性成分颗粒和赋形剂的混合物，赋形剂混合物与包衣活性成分颗粒的比例为0.4至6重量份，所述赋形剂的混合物含有：
一崩解剂；
-具有粘合特性的可溶性稀释剂，其由少于13个碳原子的多元醇组成，并且可以是平均颗粒直径为100至500μm的可直接压制的产品形式或是平均颗粒直径小于100μm的粉末形式，并且当仅有一种具有粘合特性的可溶性稀释剂时，其以可直接压制的产品的形式使用，而当有至少两种具有粘合特性的可溶性稀释剂时，一种以可直接压制的形式存在，另一种以粉末形式存在，并且多元醇可以相同，可直接压制的多元醇与粉末多元醇的比例为99/1至20/80，
-润滑剂；
-渗透剂；和
-有利地润滑剂、甜味剂、矫味剂和着色剂，
崩解剂的比例为1至15％重量，可溶性稀释剂的比例为30至90％重量，均以片剂的重量计。
2.权利要求1的片剂，其特征在于活性成分选自阿司匹林、对乙酰氨基酚和布洛芬。
3.权利要求1或2的片剂，其特征在于崩解剂选自交联羧甲基纤维素钠、交联聚乙烯基吡咯烷酮及其混合物。
4.权利要求1或2的片剂，其特征在于渗透剂选自对含水溶剂具有高亲和性的二氧化硅、麦芽糖糊精、β-环糊精及其混合物。
5.权利要求1或2的片剂，其特征在于渗透剂是沉淀法二氧化硅。
6.权利要求1或2的片剂，其特征在于渗透剂的比例为0.1至10％，以片剂的重量计。
7.权利要求1或2的片剂，其特征在于润滑剂尤其选自硬脂酸镁、十八烷基富马酸钠、硬脂酸、微粒化的聚氧乙烯二醇及其混合物。
8.权利要求1或2的片剂，其特征在于甜味剂选自天冬酰苯丙氨酸甲酯、丁磺氨钾、糖精钠、新橙皮苷双氢查耳酮及其混合物。
9.根据权利要求1或2所述的片剂，其中多元醇选自选自甘露糖醇、木糖醇、山梨糖醇和麦芽糖醇，条件是山梨糖醇不能单独使用。
10.根据权利要求1或2所述的片剂，其中可直接压制的多元醇与粉末多元醇的比例为80/20到20/80。
11.根据权利要求1或2所述的片剂，其中崩解剂的比例为2-7％重量，可溶性稀释剂的比例为40-70％重量，均以片剂的重量计。
12.根据权利要求1或2所述的片剂，其中渗透剂的比例在0.5至5％之间，以片剂的重量计。
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR98/14034 | 1998-11-06 | ||
| FR9814034A FR2785538B1 (fr) | 1998-11-06 | 1998-11-06 | Comprime a delitement rapide perfectionne |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1328446A CN1328446A (zh) | 2001-12-26 |
| CN1154476C true CN1154476C (zh) | 2004-06-23 |
Family
ID=9532493
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB998138010A Expired - Lifetime CN1154476C (zh) | 1998-11-06 | 1999-11-03 | 改进的迅速崩解片剂 |
Country Status (28)
| Country | Link |
|---|---|
| US (2) | US7067149B1 (zh) |
| EP (1) | EP1126821B1 (zh) |
| JP (2) | JP2002529392A (zh) |
| KR (1) | KR100630465B1 (zh) |
| CN (1) | CN1154476C (zh) |
| AT (1) | ATE293954T1 (zh) |
| AU (1) | AU767703B2 (zh) |
| BG (1) | BG65011B1 (zh) |
| BR (1) | BR9915110A (zh) |
| CA (1) | CA2350054C (zh) |
| CZ (1) | CZ301589B6 (zh) |
| DE (1) | DE69925016T2 (zh) |
| DK (1) | DK1126821T3 (zh) |
| EA (1) | EA004239B1 (zh) |
| ES (1) | ES2241334T3 (zh) |
| FR (1) | FR2785538B1 (zh) |
| HK (1) | HK1039891B (zh) |
| HU (1) | HU226590B1 (zh) |
| IL (1) | IL142788A (zh) |
| MX (1) | MXPA01004518A (zh) |
| NZ (1) | NZ511480A (zh) |
| PL (1) | PL194526B1 (zh) |
| PT (1) | PT1126821E (zh) |
| SI (1) | SI1126821T1 (zh) |
| SK (1) | SK284645B6 (zh) |
| TR (1) | TR200101224T2 (zh) |
| WO (1) | WO2000027357A1 (zh) |
| ZA (1) | ZA200103629B (zh) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1303989C (zh) * | 2004-10-25 | 2007-03-14 | 北京科信必成医药科技发展有限公司 | 葡萄糖酸锌口腔崩解片及其制备工艺 |
| CN111759849A (zh) * | 2020-08-04 | 2020-10-13 | 重庆康刻尔制药有限公司 | 一种抗心绞痛的药物组合物及其制备方法和应用 |
Families Citing this family (65)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2790387B1 (fr) | 1999-03-01 | 2001-05-18 | Prographarm Laboratoires | Comprime orodispersible presentant une faible friabilite et son procede de preparation |
| DE10041478A1 (de) * | 2000-08-24 | 2002-03-14 | Sanol Arznei Schwarz Gmbh | Neue pharmazeutische Zusammensetzung |
| FR2824477B1 (fr) * | 2001-05-09 | 2005-09-09 | Ethypharm Lab Prod Ethiques | Granules enrobes a base d'inhibiteur de l'enzyme de conversion de l'anfiotensine, leur procede de preparation et comprimes orodispersibles contenant les granules enrobes |
| EP1279402B1 (en) * | 2001-07-26 | 2006-11-29 | Ethypharm | Coated granules of allylamine-or benzylamine-anti-mycotics, process for preparation thereof and orodispersible tablets containing said coated granules |
| GB0123400D0 (en) | 2001-09-28 | 2001-11-21 | Novartis Ag | Organic compounds |
| US6723348B2 (en) * | 2001-11-16 | 2004-04-20 | Ethypharm | Orodispersible tablets containing fexofenadine |
| JP2005298338A (ja) * | 2002-02-27 | 2005-10-27 | Eisai Co Ltd | 速崩壊性圧縮成形製剤 |
| GB0209265D0 (en) | 2002-04-23 | 2002-06-05 | Novartis Ag | Organic compounds |
| DE10232020A1 (de) | 2002-07-04 | 2004-02-26 | Friedrich-Alexander-Universität Erlangen-Nürnberg | Neurorezeptoraktive Heteroarencarboxamide |
| DE10232113A1 (de) | 2002-07-16 | 2004-01-29 | Bayer Ag | Vardenafil Hydrochlorid Trihydrat enthaltende Arzneimittel |
| CN100337628C (zh) * | 2002-08-07 | 2007-09-19 | 王登之 | 治疗痴呆症的尼莫地平口腔崩解片及其制备方法 |
| JP5062871B2 (ja) * | 2003-05-13 | 2012-10-31 | 東和薬品株式会社 | 苦味を低減した口腔内崩壊錠剤 |
| JP2006527184A (ja) | 2003-06-06 | 2006-11-30 | エティファーム | 口腔内分散性多層錠剤 |
| FR2855756B1 (fr) * | 2003-06-06 | 2005-08-26 | Ethypharm Sa | Comprime orodispersible multicouche |
| CN100450470C (zh) * | 2003-06-28 | 2009-01-14 | 南昌弘益科技有限公司 | 口腔内快速崩解片剂及其制备方法 |
| JP5062872B2 (ja) * | 2003-08-13 | 2012-10-31 | 東和薬品株式会社 | 不快な味を低減した口腔内崩壊錠剤 |
| US8349361B2 (en) | 2003-10-15 | 2013-01-08 | Fuji Chemical Industry Co., Ltd. | Composition for rapid disintegrating tablet in oral cavity |
| JP3841804B2 (ja) * | 2003-10-15 | 2006-11-08 | 富士化学工業株式会社 | 口腔内速崩壊性錠剤用の組成物 |
| CN100438914C (zh) * | 2003-10-15 | 2008-12-03 | 富士化学工业株式会社 | 用于口腔内快速崩解的片剂的组合物 |
| DE10359528A1 (de) * | 2003-12-18 | 2005-07-28 | Schwarz Pharma Ag | (S)-2-N-Propylamino-5-hydroxytetralin als D3-agonistisches Therapeutikum |
| EP1621187A1 (en) * | 2004-07-26 | 2006-02-01 | AstraZeneca AB | Pharmaceutical multiparticulate tablet formulations and process for their preparation |
| DE102005009240A1 (de) | 2005-03-01 | 2006-09-07 | Bayer Healthcare Ag | Arzneiformen mit verbesserten pharmakokinetischen Eigenschaften |
| TWI347942B (en) * | 2005-06-22 | 2011-09-01 | Lundbeck & Co As H | Crystalline base of escitalopram and orodispersible tablets comprising escitalopram base |
| KR20080080318A (ko) * | 2005-12-20 | 2008-09-03 | 에자이 알앤드디 매니지먼트 가부시키가이샤 | 지용성 약물을 함유하는 구강내 속붕정 |
| WO2008006534A2 (en) * | 2006-07-11 | 2008-01-17 | Lek Pharmaceuticals D.D. | Multiple unit tablets |
| CN101534792B (zh) | 2006-08-04 | 2013-02-20 | 爱的发 | 包含氧可酮的粒剂和口腔崩解片剂 |
| CA2659523C (en) | 2006-08-04 | 2014-01-28 | Ethypharm | Multilayer orally disintegrating tablet |
| AR058580A1 (es) | 2006-12-20 | 2008-02-13 | Makuc Ruben Antonio | Particulas solidas comprimibles , procedimientos para obtenerlas y procedimientos para utilizar las particulas solidas en tabletas o comprimidos para la higiene corporal |
| FR2910319B1 (fr) | 2006-12-20 | 2011-06-03 | Substipharm Dev | Formulations pharmaceutiques dispersibles contenant de la fluoxetine |
| WO2008089772A1 (fr) * | 2007-01-22 | 2008-07-31 | Crd Saidal | Formulation d'un comprime orodispersible a base d'acide acetylsalicylique enrobe |
| WO2008089773A1 (fr) * | 2007-01-22 | 2008-07-31 | Crd Saidal | Formulation d'une matrice a desintegration rapide |
| US20080181932A1 (en) * | 2007-01-30 | 2008-07-31 | Drugtech Corporation | Compositions for oral delivery of pharmaceuticals |
| CA2617688C (en) * | 2007-02-22 | 2015-08-18 | Alpex Pharma S.A. | Solid dosage formulations containing weight-loss drugs |
| CA2680536A1 (en) | 2007-03-13 | 2008-10-09 | Dainippon Sumitomo Pharma Co., Ltd. | Oral disintegrating tablet |
| JP5766899B2 (ja) * | 2007-04-11 | 2015-08-19 | ニプロ株式会社 | 口腔内崩壊剤及びその製造方法 |
| KR101109633B1 (ko) * | 2007-08-03 | 2012-01-31 | 제이더블유중외제약 주식회사 | 활성성분의 코팅막이 보호되는 구강내붕해제형을 제조하기위한 조성물 |
| FR2920311B1 (fr) * | 2007-08-31 | 2010-06-18 | Galenix Innovations | Composition solide, orodispersible et/ou dispersible, sans excipient a effet notoire et son procede de preparation |
| JP2009114113A (ja) * | 2007-11-06 | 2009-05-28 | Nipro Corp | 口腔内崩壊錠及びその製造方法 |
| DE102008014237A1 (de) * | 2008-03-14 | 2009-09-17 | J. Rettenmaier & Söhne Gmbh + Co. Kg | Direktverpressbares Tablettierhilfsmittel |
| CN102083418A (zh) * | 2008-04-24 | 2011-06-01 | 伊万斯彻有限公司 | 口服避孕药剂及其制备方法 |
| EP2385769A4 (en) * | 2008-12-15 | 2014-08-20 | Valeant Pharmaceuticals Luxembourg S R L | QUICKLY SOLUBLE VITAMIN FORMULATION AND METHOD FOR THEIR USE |
| ES2422281T3 (es) | 2009-04-09 | 2013-09-10 | E Pharma Trento Spa | Granulado para la formulación de comprimidos bucodispersables |
| CN102396237B (zh) * | 2009-04-14 | 2014-11-26 | 松下电器产业株式会社 | 影像显示装置、影像收看用眼镜以及具备这些的系统 |
| FR2962550B1 (fr) | 2010-07-06 | 2013-06-14 | Ethypharm Sa | Methode pour lutter contre la soumission chimique, utilisation d'agent colorant pour lutter contre la soumission chimique et composition pharmaceutique permettant la mise en oeuvre de la methode |
| FR2962331B1 (fr) | 2010-07-06 | 2020-04-24 | Ethypharm | Forme pharmaceutique pour lutter contre la soumission chimique, methode la mettant en oeuvre |
| CN102440971A (zh) * | 2010-10-15 | 2012-05-09 | 重庆市力扬医药开发有限公司 | 伊潘立酮口腔崩解片 |
| US10004691B2 (en) | 2013-05-21 | 2018-06-26 | Takeda Pharmaceuticals Company Limited | Orally disintegrable tablet |
| JP6128160B2 (ja) * | 2015-05-07 | 2017-05-17 | ニプロ株式会社 | 口腔内崩壊錠の製造方法 |
| CN106389339B (zh) * | 2015-08-12 | 2020-08-04 | 北京科信必成医药科技发展有限公司 | 一种阿司匹林无水吞服掩味颗粒及其制备方法 |
| FR3055800B1 (fr) * | 2016-09-15 | 2020-06-26 | Unither Pharmaceuticals | Composition solide a ingestion rapide et deglutition facilitee, sous forme de particules solides non agglomerees, comprenant deux differents types de particules |
| US10543205B2 (en) | 2016-11-18 | 2020-01-28 | Fertin Pharma A/S | Oral delivery vehicle containing nicotine |
| US10632076B2 (en) | 2016-11-18 | 2020-04-28 | Fertin Pharma A/S | Tablet comprising separate binder and erythritol |
| CA3002181C (en) * | 2017-04-18 | 2020-05-05 | Kashiv Pharma Llc | Food independent immediate release drug formulation with abuse deterrence and overdose protection |
| US11090263B2 (en) | 2018-05-22 | 2021-08-17 | Fertin Pharma A/S | Tableted chewing gum suitable for active pharmaceutical ingredients |
| US11058633B2 (en) | 2018-05-17 | 2021-07-13 | Fertin Pharma A/S | Disintegrating oral tablet suitable for active pharmaceutical ingredients |
| US11135157B2 (en) | 2018-05-17 | 2021-10-05 | Fertin Pharma A/S | Oral tablet for delivery of active ingredients to the throat |
| US20190350858A1 (en) | 2018-05-17 | 2019-11-21 | Fertin Pharma A/S | Oral tablet for delivery of active ingredients to the gastrointestinal tract |
| US11096895B2 (en) | 2018-05-17 | 2021-08-24 | Fertin Pharma A/S | Oral tablet suitable for active pharmaceutical ingredients |
| US11052047B2 (en) | 2018-05-17 | 2021-07-06 | Fertin Pharma A/S | Oral tablet suitable for fast release of active pharmaceutical ingredients |
| US11058641B2 (en) | 2018-05-17 | 2021-07-13 | Fertin Pharma A/S | Oral tablet for taste masking of active ingredients |
| US11096896B2 (en) | 2018-05-17 | 2021-08-24 | Fertin Pharma A/S | Tablet dosage form for buccal absorption of active ingredients |
| US11096894B2 (en) | 2018-05-17 | 2021-08-24 | Fertin Pharma A/S | Oral tablet for induced saliva generation |
| US10925853B2 (en) | 2019-04-17 | 2021-02-23 | Nordiccan A/S | Oral cannabinoid tablet |
| FR3099881B1 (fr) * | 2019-08-13 | 2022-08-26 | Ethypharm Sa | Comprimé orodispersible d’opioide à faible dosage et son procédé de préparation. |
| FR3095762A1 (fr) * | 2020-05-07 | 2020-11-13 | Unither Pharmaceuticals | Composition solide à ingestion rapide et déglutition facilitée, sous forme de particules solides non agglomérées, comprenant deux différents types de particules |
Family Cites Families (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4832956A (en) * | 1985-09-25 | 1989-05-23 | Gerhard Gergely | Disintegrating tablet and process for its preparation |
| US4837031A (en) * | 1987-09-17 | 1989-06-06 | Mallinckrodt, Inc. | Compositions containing ibuprofen |
| US5084278A (en) * | 1989-06-02 | 1992-01-28 | Nortec Development Associates, Inc. | Taste-masked pharmaceutical compositions |
| NZ234587A (en) * | 1989-08-04 | 1991-11-26 | Mcneil Ppc Inc | A chewable pharmaceutical tablet of compressed coated granules |
| US5064656A (en) * | 1989-11-14 | 1991-11-12 | Dr. Gergely & Co. | Uncoated pharmaceutical reaction tablet |
| JPH05506011A (ja) * | 1990-04-11 | 1993-09-02 | ジ・アップジョン・カンパニー | 流動床コーティングによるイブプロフェンの味覚マスキング |
| CA2103443C (en) * | 1991-05-28 | 1998-12-22 | Robert P. Geyer | Chewable drug-delivery composition |
| FR2679451B1 (fr) * | 1991-07-22 | 1994-09-09 | Prographarm Laboratoires | Comprime multiparticulaire a delitement rapide. |
| US5324848A (en) * | 1993-03-11 | 1994-06-28 | Nec Research Institute, Inc. | Vanadium phosphate materials |
| CA2128820A1 (en) * | 1993-07-27 | 1995-01-28 | Walter G. Gowan, Jr. | Rapidly disintegrating pharmaceutical dosage form and process for preparation thereof |
| ZA945944B (en) * | 1993-08-13 | 1996-02-08 | Eurand America Inc | Procedure for encapsulating nsaids |
| PL187160B1 (pl) * | 1994-01-31 | 2004-05-31 | Yamanouchi Pharma Co Ltd | Sposób wytwarzania rozpuszczalnej wewnątrzustnie formowanej tłocznie wypraski |
| US5567439A (en) * | 1994-06-14 | 1996-10-22 | Fuisz Technologies Ltd. | Delivery of controlled-release systems(s) |
| US5994348A (en) * | 1995-06-07 | 1999-11-30 | Sanofi | Pharmaceutical compositions containing irbesartan |
| EP0839526A3 (en) * | 1996-10-31 | 1999-01-07 | Takeda Chemical Industries, Ltd. | Solid pharmaceutical preparation with fast buccal disintegration or dissolution |
| JPH10167958A (ja) * | 1996-12-09 | 1998-06-23 | Sankyo Co Ltd | ロキソプロフェンナトリウム類を含有する口腔内速溶性製剤及びその製造方法 |
| FR2766089B1 (fr) * | 1997-07-21 | 2000-06-02 | Prographarm Lab | Comprime multiparticulaire perfectionne a delitement rapide |
| US5869098A (en) * | 1997-08-20 | 1999-02-09 | Fuisz Technologies Ltd. | Fast-dissolving comestible units formed under high-speed/high-pressure conditions |
| US6465009B1 (en) * | 1998-03-18 | 2002-10-15 | Yamanouchi Pharmaceutical Co., Ltd. | Water soluble polymer-based rapidly dissolving tablets and production processes thereof |
| US6099865A (en) * | 1998-07-08 | 2000-08-08 | Fmc Corporation | Croscarmellose taste masking |
-
1998
- 1998-11-06 FR FR9814034A patent/FR2785538B1/fr not_active Expired - Lifetime
-
1999
- 1999-11-03 DE DE69925016T patent/DE69925016T2/de not_active Expired - Lifetime
- 1999-11-03 MX MXPA01004518A patent/MXPA01004518A/es active IP Right Grant
- 1999-11-03 CN CNB998138010A patent/CN1154476C/zh not_active Expired - Lifetime
- 1999-11-03 CZ CZ20011433A patent/CZ301589B6/cs not_active IP Right Cessation
- 1999-11-03 ES ES99954046T patent/ES2241334T3/es not_active Expired - Lifetime
- 1999-11-03 NZ NZ511480A patent/NZ511480A/en not_active IP Right Cessation
- 1999-11-03 WO PCT/FR1999/002681 patent/WO2000027357A1/fr active IP Right Grant
- 1999-11-03 CA CA2350054A patent/CA2350054C/fr not_active Expired - Lifetime
- 1999-11-03 EP EP99954046A patent/EP1126821B1/fr not_active Expired - Lifetime
- 1999-11-03 TR TR2001/01224T patent/TR200101224T2/xx unknown
- 1999-11-03 KR KR1020017005750A patent/KR100630465B1/ko active IP Right Grant
- 1999-11-03 SI SI9930794T patent/SI1126821T1/xx unknown
- 1999-11-03 SK SK567-2001A patent/SK284645B6/sk not_active IP Right Cessation
- 1999-11-03 EA EA200100492A patent/EA004239B1/ru not_active IP Right Cessation
- 1999-11-03 BR BR9915110-3A patent/BR9915110A/pt not_active Application Discontinuation
- 1999-11-03 DK DK99954046T patent/DK1126821T3/da active
- 1999-11-03 PT PT99954046T patent/PT1126821E/pt unknown
- 1999-11-03 PL PL99347550A patent/PL194526B1/pl unknown
- 1999-11-03 JP JP2000580588A patent/JP2002529392A/ja active Pending
- 1999-11-03 US US09/830,946 patent/US7067149B1/en not_active Expired - Lifetime
- 1999-11-03 AU AU10507/00A patent/AU767703B2/en not_active Expired
- 1999-11-03 HU HU0104393A patent/HU226590B1/hu unknown
- 1999-11-03 AT AT99954046T patent/ATE293954T1/de active
-
2001
- 2001-04-24 IL IL142788A patent/IL142788A/en not_active IP Right Cessation
- 2001-04-25 BG BG105475A patent/BG65011B1/bg unknown
- 2001-05-04 ZA ZA200103629A patent/ZA200103629B/xx unknown
-
2002
- 2002-02-01 HK HK02100788.4A patent/HK1039891B/zh not_active IP Right Cessation
-
2006
- 2006-03-06 US US11/368,767 patent/US7695735B2/en not_active Expired - Fee Related
-
2011
- 2011-09-12 JP JP2011198153A patent/JP2012001557A/ja active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1303989C (zh) * | 2004-10-25 | 2007-03-14 | 北京科信必成医药科技发展有限公司 | 葡萄糖酸锌口腔崩解片及其制备工艺 |
| CN111759849A (zh) * | 2020-08-04 | 2020-10-13 | 重庆康刻尔制药有限公司 | 一种抗心绞痛的药物组合物及其制备方法和应用 |
| CN111759849B (zh) * | 2020-08-04 | 2021-10-01 | 重庆康刻尔制药股份有限公司 | 一种抗心绞痛的药物组合物及其制备方法和应用 |
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN1154476C (zh) | 改进的迅速崩解片剂 | |
| CN1183903C (zh) | 低易碎性的口服溶散片及其生产方法 | |
| CN1186098C (zh) | 在口腔中迅速崩解的片剂 | |
| CN1168440C (zh) | 左旋多巴/卡比多巴/恩他卡朋药物制剂 | |
| JP5788056B2 (ja) | 低置換度ヒドロキシプロピルセルロース水分散液を用いた湿式造粒打錠法 | |
| CN1225017A (zh) | 可迅速崩解的压模物质及其生产方法 | |
| CN1317309A (zh) | 快速溶化口服药物制剂 | |
| JP2002060338A (ja) | 直接圧縮された固体剤形 | |
| CN1042299C (zh) | 二脱氧嘌呤核苷类药物改进的口服剂型的制备方法 | |
| CN1224348A (zh) | 用于制备含有大量药物的快速崩解和快速溶解的组合物的颗粒 | |
| CN1622804A (zh) | 包含阿戈美拉汀的可在口中分散的药物组合物 | |
| CN1198615C (zh) | 可再现释放活性组分加替沙星或其可药用盐或水合物的口服药物剂型 | |
| AU2007328390B2 (en) | Method of forming a tablet comprising pre-blend of ibupropen and silicon dioxide | |
| CN1301151A (zh) | 控释制剂 | |
| CN1278688C (zh) | 包含伊伐布雷定的可在口中分散的药物组合物 | |
| CN1700910A (zh) | 甲福明控释片剂 | |
| EA006008B1 (ru) | Способ получения таблеток из фармацевтически активных веществ | |
| CN1658898A (zh) | 包含培哚普利的口腔分散药物组合物 | |
| CN1568991A (zh) | 一种地氯雷他定分散片及其制备方法 | |
| JP2901635B2 (ja) | アルギネートとポリアクリレートの混合物及びその使用 | |
| CN1732905A (zh) | 可直接压片的木糖醇颗粒及其制法 | |
| JP2669517B2 (ja) | ロキソプロフェン・ナトリウム含有固形製剤 | |
| CN1582927A (zh) | 一种尼莫地平口腔崩解片剂及其制备方法 | |
| CN1042832A (zh) | 药物组合物及其制备方法 | |
| US20080214677A1 (en) | Chitosan-Silicon Dioxide Coprecipitate and Use as Excipient in Solid Dosage Forms |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| C10 | Entry into substantive examination | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| ASS | Succession or assignment of patent right |
Owner name: EDVA Free format text: FORMER OWNER: ROOM #, AIDIKEAIDIFAMUYAOPINSHIYAN Effective date: 20030604 |
|
| C41 | Transfer of patent application or patent right or utility model | ||
| TA01 | Transfer of patent application right |
Effective date of registration: 20030604 Address after: Wudang, France Applicant after: Ai Defa Address before: Wudang, France Applicant before: LABORATOIRES DES PRODUITS ETHIQUES ETHYPHARM |
|
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CX01 | Expiry of patent term |
Granted publication date: 20040623 |
|
| CX01 | Expiry of patent term |