CN1251758A - 口服崩解的药物制剂 - Google Patents
口服崩解的药物制剂 Download PDFInfo
- Publication number
- CN1251758A CN1251758A CN99106617A CN99106617A CN1251758A CN 1251758 A CN1251758 A CN 1251758A CN 99106617 A CN99106617 A CN 99106617A CN 99106617 A CN99106617 A CN 99106617A CN 1251758 A CN1251758 A CN 1251758A
- Authority
- CN
- China
- Prior art keywords
- tablet
- pharmaceutical preparation
- disintegrate
- nafei
- preparation
- 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.)
- Pending
Links
- 238000002360 preparation method Methods 0.000 title claims description 10
- 239000011230 binding agent Substances 0.000 claims description 25
- 238000000034 method Methods 0.000 claims description 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 17
- 239000003513 alkali Substances 0.000 claims description 13
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 13
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 11
- ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical group [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 claims description 8
- 229910000013 Ammonium bicarbonate Inorganic materials 0.000 claims description 8
- 235000012538 ammonium bicarbonate Nutrition 0.000 claims description 8
- 239000001099 ammonium carbonate Substances 0.000 claims description 8
- 239000000203 mixture Substances 0.000 claims description 8
- 238000002156 mixing Methods 0.000 claims description 6
- 229930006000 Sucrose Natural products 0.000 claims description 5
- 239000000853 adhesive Substances 0.000 claims description 5
- 230000001070 adhesive effect Effects 0.000 claims description 5
- 239000005720 sucrose Substances 0.000 claims description 5
- 239000002202 Polyethylene glycol Substances 0.000 claims description 4
- 229920001223 polyethylene glycol Polymers 0.000 claims description 4
- -1 sucrose ester Chemical class 0.000 claims description 4
- 201000001881 impotence Diseases 0.000 claims description 3
- 239000000155 melt Substances 0.000 claims description 3
- 150000001298 alcohols Chemical class 0.000 claims description 2
- 235000014113 dietary fatty acids Nutrition 0.000 claims description 2
- 239000000194 fatty acid Substances 0.000 claims description 2
- 229930195729 fatty acid Natural products 0.000 claims description 2
- 150000004665 fatty acids Chemical class 0.000 claims description 2
- 150000001875 compounds Chemical class 0.000 abstract description 6
- BNRNXUUZRGQAQC-UHFFFAOYSA-N sildenafil Chemical compound CCCC1=NN(C)C(C(N2)=O)=C1N=C2C(C(=CC=1)OCC)=CC=1S(=O)(=O)N1CCN(C)CC1 BNRNXUUZRGQAQC-UHFFFAOYSA-N 0.000 abstract description 6
- 229960003310 sildenafil Drugs 0.000 abstract description 3
- 239000006186 oral dosage form Substances 0.000 abstract description 2
- 239000012458 free base Substances 0.000 abstract 1
- 239000008194 pharmaceutical composition Substances 0.000 abstract 1
- 235000019640 taste Nutrition 0.000 description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 239000004615 ingredient Substances 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- 239000000463 material Substances 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 5
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 239000002552 dosage form Substances 0.000 description 5
- 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 description 4
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 4
- 229930195725 Mannitol Natural products 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- 239000011248 coating agent Substances 0.000 description 4
- 238000000576 coating method Methods 0.000 description 4
- 239000000796 flavoring agent Substances 0.000 description 4
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 4
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 4
- 239000000594 mannitol Substances 0.000 description 4
- 235000010355 mannitol Nutrition 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 3
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 229910001873 dinitrogen Inorganic materials 0.000 description 3
- MVPICKVDHDWCJQ-UHFFFAOYSA-N ethyl 3-pyrrolidin-1-ylpropanoate Chemical compound CCOC(=O)CCN1CCCC1 MVPICKVDHDWCJQ-UHFFFAOYSA-N 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 239000000314 lubricant Substances 0.000 description 3
- 235000019359 magnesium stearate Nutrition 0.000 description 3
- 229910052751 metal Inorganic materials 0.000 description 3
- 239000002184 metal Substances 0.000 description 3
- 229940050929 polyethylene glycol 3350 Drugs 0.000 description 3
- 238000010926 purge Methods 0.000 description 3
- 229940045902 sodium stearyl fumarate Drugs 0.000 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 description 2
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 2
- 208000010228 Erectile Dysfunction Diseases 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- 229920002562 Polyethylene Glycol 3350 Polymers 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 235000010980 cellulose Nutrition 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 235000019634 flavors Nutrition 0.000 description 2
- 235000013355 food flavoring agent Nutrition 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 229940085605 saccharin sodium Drugs 0.000 description 2
- 239000000377 silicon dioxide Substances 0.000 description 2
- 235000012239 silicon dioxide Nutrition 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000007909 solid dosage form Substances 0.000 description 2
- 235000013599 spices Nutrition 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 239000003232 water-soluble binding agent Substances 0.000 description 2
- DSSYKIVIOFKYAU-XCBNKYQSSA-N (R)-camphor Chemical compound C1C[C@@]2(C)C(=O)C[C@@H]1C2(C)C DSSYKIVIOFKYAU-XCBNKYQSSA-N 0.000 description 1
- QIZPVNNYFKFJAD-UHFFFAOYSA-N 1-chloro-2-prop-1-ynylbenzene Chemical compound CC#CC1=CC=CC=C1Cl QIZPVNNYFKFJAD-UHFFFAOYSA-N 0.000 description 1
- RFVNOJDQRGSOEL-UHFFFAOYSA-N 2-hydroxyethyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCCO RFVNOJDQRGSOEL-UHFFFAOYSA-N 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 239000005913 Maltodextrin Substances 0.000 description 1
- 229920002774 Maltodextrin Polymers 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 229920002594 Polyethylene Glycol 8000 Polymers 0.000 description 1
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 235000019658 bitter taste Nutrition 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 238000007664 blowing Methods 0.000 description 1
- 239000010238 camphora Substances 0.000 description 1
- 229940025250 camphora Drugs 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 235000013877 carbamide Nutrition 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 238000005352 clarification Methods 0.000 description 1
- 239000004927 clay Substances 0.000 description 1
- 229920006037 cross link polymer Polymers 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 150000002016 disaccharides Chemical class 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- POULHZVOKOAJMA-UHFFFAOYSA-M dodecanoate Chemical compound CCCCCCCCCCCC([O-])=O POULHZVOKOAJMA-UHFFFAOYSA-M 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 229940070765 laurate Drugs 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229940035034 maltodextrin Drugs 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000002398 materia medica Substances 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
- 239000003094 microcapsule Substances 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 229920001206 natural gum Polymers 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 229940126701 oral medication Drugs 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 210000002381 plasma Anatomy 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 235000011185 polyoxyethylene (40) stearate Nutrition 0.000 description 1
- 239000001194 polyoxyethylene (40) stearate Substances 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 210000003296 saliva Anatomy 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 208000012201 sexual and gender identity disease Diseases 0.000 description 1
- 208000015891 sexual disease Diseases 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 229940035023 sucrose monostearate Drugs 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- MWOOGOJBHIARFG-UHFFFAOYSA-N vanillin Chemical compound COC1=CC(C=O)=CC=C1O MWOOGOJBHIARFG-UHFFFAOYSA-N 0.000 description 1
- FGQOOHJZONJGDT-UHFFFAOYSA-N vanillin Natural products COC1=CC(O)=CC(C=O)=C1 FGQOOHJZONJGDT-UHFFFAOYSA-N 0.000 description 1
- 235000012141 vanillin Nutrition 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
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—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
- A61K9/2095—Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/10—Drugs for genital or sexual disorders; Contraceptives for impotence
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- Zoology (AREA)
- Physiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Reproductive Health (AREA)
- Endocrinology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Nutrition Science (AREA)
- Gynecology & Obstetrics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Silicon Polymers (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
本发明涉及化合物昔得那非(sildenafil)的新的药物制剂,特别是含有以其游离碱形式存在的昔得那非的迅速崩解口服剂型。
Description
本发明涉及化合物昔得那非(sildenafil)的新的药物制剂，特别是含有以其游离碱形式存在的昔得那非的迅速崩解口服剂型。
欧洲专利EP-B-0463756公开了并且要求保护化合物昔得那非(5-[2-乙氧基-5-(4-甲基哌嗪-1-基磺酰基)-苯基]-1，6-二氢-1-甲基-3-丙基吡唑并[4，3-d]嘧啶-7-酮)和其可药用盐。国际专利申请WO94/28902公开了并且要求保护其在治疗男性勃起机能障碍(阳痿)和女性性功能障碍中的用途。象大多数朝着人类医疗用途发展的化合物一样，对于此化合物，口服给药是优选的，为了达到这个目的并且能保证迅速吸收和好的生物利用度，可溶性盐是最初优选的；这使得人们选择了具有很好的溶解性并且无毒的柠檬酸盐，其已经进入临床试验阶段并且在一些国家已经被批准上市。
虽然经证明此化合物的柠檬酸盐能以常规的胶囊或片剂形式非常令人满意地给药，但是人们注意到此产品确实具有不可口的苦味。
对于一些给药，人们希望有能在口中迅速崩解的制剂。增加药物在口中的崩解速度有利于对一些病人给药，并且能提高活性组分的吸收速度。美国专利3885026和4134943公开了多孔并且能迅速崩解的片剂的实例。欧洲专利EP-B-0620728公开了强度增加的、多孔的、并且能迅速崩解的片剂。这类片剂是用可熔性粘合剂、崩解剂和挥发性成份制成的，其中挥发性成份在片剂组分压片后从片剂中挥发出去以形成多孔片剂。
上述快速崩解固体剂型的一个问题是，当剂型在口中崩解时病人会尝到药用活性组分的味道。对于一些药用活性组分，如果其味道仅有轻微的不适，通过使用甜味剂或调味剂来掩饰其味道，可使其被病人接受。然而，这一方法不能全部掩饰住昔得那非柠檬酸盐的味道。另一掩饰味道的方法是使用在口中能保护活性组分的聚合物包衣将活性组分封闭在微胶囊中；然而此技术即复杂成本又高，还会带来生物等效问题。WO96/13252公开了另一种方法，即将药用活性组分以难溶于水的形式使用。虽然这种方法在理论上是可行的，但是在实践中，通常难以找到使活性组分的溶解性低到在口中完全没有味道的形式，因为舌头甚至能感觉到非常少量的物质，尤其是具有强烈味道的物质。此外，为了使活性组分吸收到血液中，也需要在药物吞咽后活性组分的不溶形式能立即溶解。
根据本发明，我们惊奇地发现，昔得那非在其游离碱的形式下，在水以及唾液中具有非常小的溶解度，这使其特别适于以口服崩解的剂型使用，而基本上没有味道。此外，我们现在发现，出乎意料的是，昔得那非游离碱除了具有低的溶解度以外，还能从胃或胃肠道中被有效地吸收，并且这种制剂能向血浆提供与昔得那非柠檬酸盐口服液或昔得那非柠檬酸盐的常规片剂或胶囊基本上相同的活性组分水平。
因此，本发明提供了一种口服崩解的药物制剂，其中含有昔得那非游离碱和可药用载体。
特别优选的是口服崩解的药物制剂，其中含有昔得那非游离碱和能在口中迅速崩解的可药用载体。
本发明中使用的术语“迅速崩解”，对于口服药物制剂表示，片剂、囊剂或其它固体剂型在37℃的水中能在60秒或少于60秒的时间内崩解，优选5-10秒或更少。任何具体制剂的崩解度都可以用标准药学方法测定，例如在WO96/13252中描述的方法，和与其相似的、在英国专利1548022中描述的英国药典(B.P.)1973版的片剂崩解测试。这些测试方法在下面全文引用。
在本发明的一个具体实施方案中，可以使用水溶性粘合剂和挥发性组分制备含有昔得那非游离碱的迅速崩解口服固体剂型，其中挥发性成份在片剂组分混合并压片后从片剂中挥发出去以形成高度多孔的片剂。
在此实施方案中，片剂是按照EP-B-0620728中的方法制备的。此方法包括以下步骤(a)将水溶性及可熔性粘合剂、至少一种赋形剂、和昔得那非游离碱混合并压制成片，(b)将所说片剂中的粘合剂熔化，(c)使所说的粘合剂凝固。
用于增加片剂成品强度的水溶性及可熔性粘合剂通常的熔点是20-100℃，优选40-70℃。此粘合剂的熔点通常高于20℃，因为各组分的混合通常在此温度进行并且粘合剂在此混合温度应保持固体形态。当然，如果混合是在较低温度下进行的，在此混合温度能保持固体形态的熔点较低的粘合剂也可以使用。
粘合剂的熔点温度一般不高于100℃，因为粘合剂应当在药用活性组分的活性不受不利影响的温度下熔化。例如，粘合剂应当在低于药用活性组分以及任意含有的赋形剂分解的温度下熔化。
在本发明的这个实施方案的片剂中，水溶性及可熔性粘合剂加入的量为5％-40％重量比，优选8％-25％重量比，其中重量百分比是基于片剂的重量。应当避免加入过量的水溶性及可熔性粘合剂，因为片剂可能在熔化时变形，而如果粘合剂使用的量不足时，就不能获得所需的强度。
合适的水溶性及可熔性粘合剂包括分子量约为1500-约20000的聚乙二醇(PEG)，如PEG 3350(熔点58℃)和PEG 8000(熔点62℃)，蔗糖酯如蔗糖一硬脂酸酯(熔点49-56℃)和蔗糖一棕榈酸酯(熔点40-48℃)，乙氧基化脂肪酸如聚氧乙烯(40)硬脂酸酯(熔点47℃)(Myrj-52S)，乙氧基化醇如聚氧乙烯(23)月桂酸酯。这些可熔性及水溶性粘合剂使片剂在口中的崩解速度增加，例如小于10秒的快速崩解速度，以及快至1-5秒的崩解速度。
水溶性及可熔性粘合剂可以与一种或多种赋形剂和药用活性组分以任意顺序混合。粘合剂可以以干燥的形式或在合适的溶剂如乙醇、异丙醇或水中与其它组分混合。将溶解的粘合剂加到其它片剂组分中以形成湿颗粒。如果需要的话，昔得那非在湿颗粒干燥后加入。通常，在干燥的颗粒压制成片以前，将混合的片剂组分磨碎并且与片剂润滑剂混合。
用于本发明片剂中的赋形剂是本领域已知的常规赋形剂，即如Remington药物学(Pharmaceutical Sciences)第18版(1990)、特别是在第1633-1638页中描述的赋形剂。它们使制片前的片剂和片剂成品具有加工和压片所需的特性。赋形剂的实例有稀释剂、粘合剂、润滑剂、调味剂、和甜味剂。用于本发明的具体的稀释剂是水溶性稀释剂，例如甘露糖醇、木糖醇、蔗糖、乳糖、和氯化钠。适用于本发明的粘合剂，除了所用的水溶性及可熔性粘合剂以外，还有具有其粘合特性的粘合剂，包括淀粉、明胶、微晶纤维素和糖如蔗糖、葡萄糖、葡萄糖、右旋糖和乳糖。如上所清楚描述的，同一赋形剂可以在同一片剂中起不同的作用。
可以添加崩解剂以增加口服摄取后片剂的崩解速度。崩解剂的实例有纤维素如羧甲基纤维素、淀粉、粘土、藻胶、树胶和交联聚合物如交联聚乙烯吡咯烷酮(PVP-XL)。
在本发明此方面的具体实施方案中，片剂中含有挥发性组分。片剂组分混合以及压片后，通过在常压或减压条件下加热，将挥发性组分从片剂中挥发出去以形成多孔片剂。在一个优选的制备方法中，将片剂在连续氮气吹洗下加热到50-60℃直到挥发性组分全部经升华挥发出去。使用氮气吹洗有助于保护昔得那非在这些条件下免于降解，然而，对于50-55℃，也可使用空气吹洗。合适的挥发性组分包括能升华的物质例如甲醇、樟脑、尿素、和香草醛、以及在等于或低于粘合剂的熔点能分解的物质如碳酸氢铵。挥发性组分的用量为1％-95％重量比，这是基于混合的片剂组分的重量。例如，当使用碳酸氢铵时，其用量为50％-90％重量比，当使用甲醇时，其典型用量为30％-55％重量比。挥发性组分优选在熔化阶段挥发出去，即当压制成的片剂在粘合剂的熔点以上加热一段时间足以使可熔性粘合剂熔化并且除去挥发性组分时。当使用甲醇时，通过在真空中加热到约40℃来除去挥发性组分；当使用碳酸氢铵时，通过在真空中加热到60℃来除去挥发性组分。
用任一方法制备的片剂都可以包上一薄层包衣材料以改善片剂的表面整体性。合适的包衣材料包括二糖如蔗糖、多糖如麦芽糖糊精和果胶、和纤维素衍生物如羟丙基甲基纤维素和羟丙基纤维素，然而，任一包衣都应充分薄并且是水溶性的，以免妨碍片剂在口中的迅速崩解能力。
下面用实施例来更具体地描述本发明：实施例1
按照如下所示的欧洲专利EP-B-0620728中的方法，制备高度多孔的、能在口中迅速崩解的片剂：
将组分2、3、4和5混合并且用乙醇制成湿颗粒。将干燥的颗粒磨碎并且与组分1、6、7、8、9和10混合。最后，将组分11与得到的混合物混合。将最终的混合物压制成直径为12.7mm(0.5英寸)的片剂。将片剂在连续氮气吹洗下在50-60℃加热直到碳酸氢铵全部升华。
注解：(1)在最终的剂型中不含有成孔剂。(4)PEG 3350是一种可溶性聚乙二醇，熔点为58℃。在此片剂中用作可熔性粘合剂。(11)片剂润滑剂
| 组分 | mg/片 | |
| 1 | 昔得那非(游离碱) | 50.00 |
| 2 | 碳酸氢铵 | 308.00 |
| 3 | 甘露糖醇 | 44.7 |
| 4 | 聚乙二醇3350 | 5.6 |
| 5 | 羟丙基纤维素 | 11.2 |
| 6 | 糖精钠 | 3.6 |
| 7 | 可压缩的糖 | 19.00 |
| 8 | 二氧化硅 | 2.4 |
| 9 | 香蕉味香料 | 23.90 |
| 10 | 硬脂酰延胡索酸钠 | 4.8 |
| 11 | 硬脂酸镁 | 4.8 |
此片剂具有高度多孔的结构，口服给药时，在口中能迅速崩解并且具有可接受味道。实施例2
按照实施例1中的方法制备片剂，其中赋形剂以选自下面范围的量使用：
| 组分 | mg/片 | |
| 1 | 昔得那非(游离碱) | 50 |
| 2 | 碳酸氢铵 | 240-360 |
| 3 | 甘露糖醇 | 40-100 |
| 4 | 聚乙二醇3350 | 5-20 |
| 5 | 羟丙基纤维素 | 0-15 |
| 6 | 糖精钠 | 0-6 |
| 7 | 可压缩的糖 | 0-40 |
| 8 | 二氧化硅 | 0-5 |
| 9 | 香蕉味香料 | 0-50 |
| 10 | 硬脂酰延胡索酸钠 | 2-7 |
| 11 | 硬脂酸镁 | 2-7 |
获得了具有高度多孔的结构、口服给药时在口中能迅速崩解并且具有可接受味道的片剂。实施例3
按照实施例1中的方法制备片剂，其中赋形剂以选自下面范围的量使用：
| 组分 | mg/片 | |
| 1 | 昔得那非(游离碱) | 50 |
| 2 | 碳酸氢铵 | 240-360 |
| 3 | 甘露糖醇 | 40-100 |
| 4 | 聚乙二醇3350 | 5-20 |
| 5 | 羟丙基纤维素 | 0-15 |
| 6 | 硬脂酰延胡索酸钠 | 2-7 |
| 7 | 硬脂酸镁 | 2-7 |
获得了具有高度多孔的结构、口服给药时在口中能迅速崩解并且具有可接受味道的片剂。崩解速度的测定仪器
一根玻璃管或合适的塑料管，管长80-100mm，内径28mm，外径30-31mm，在底部末端安装上符合No.1.70筛要求的不锈金属丝网圆盘(英国药典(B.P.)1973版第A136页)，以形成吊篮。
一个玻璃圆筒，具有平底，内径约为45mm，其中含有水并且至少15cm深，水温为36-38℃。
将吊篮悬浮在圆筒中央，使其能以恒定的方式上下重复移动，在最高处金属丝网正好接触到水面，在最低处吊篮的上边缘正好保持在水的澄清部位。方法
将一个药片放置在吊篮中，将吊篮以每分钟完成上下移动重复30次的速度上下移动。当金属丝网上面没有任何颗粒时，剂型崩解完全。
Claims (9)
1.口服崩解的药物制剂，其中含有昔得那非游离碱和可药用载体。
2.根据权利要求1的口服崩解的药物制剂，其中含有昔得那非游离碱和在口中能迅速崩解的可药用载体。
3.根据权利要求2的药物制剂，其中所说的制剂是按照包括如下步骤的方法制备的：(a)将水溶性及可熔性粘合剂、至少一种赋形剂、和昔得那非游离碱混合并压制成片，(b)将所说片剂中的粘合剂熔化，(c)使所说的粘合剂凝固。
4.根据权利要求3的药物制剂，其中所说的粘合剂是聚乙二醇、蔗糖酯、乙氧基化脂肪酸或乙氧基化醇。
5.根据权利要求3的药物制剂，其中所说的步骤(a)包括与在压片步骤后从片剂中除去的挥发性组分混合。
6.根据权利要求5的药物制剂，其中所说的挥发性组分是碳酸氢铵。
7.治疗人性功能障碍的方法，包括用如权利要求1所述的口服崩解的药物制剂给药，并且让所说的制剂在口中崩解。
8.根据权利要求7的方法，其中将药物制剂对男性阳痿患者给药。
9.根据权利要求7的方法，其中将药物制剂对女性给药。
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US8564698P | 1998-05-15 | 1998-05-15 | |
| US085,646 | 1998-05-15 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1251758A true CN1251758A (zh) | 2000-05-03 |
Family
ID=22193027
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN99106617A Pending CN1251758A (zh) | 1998-05-15 | 1999-05-14 | 口服崩解的药物制剂 |
Country Status (32)
| Country | Link |
|---|---|
| US (1) | US20020002172A1 (zh) |
| EP (1) | EP0960621A3 (zh) |
| JP (1) | JPH11349483A (zh) |
| KR (1) | KR19990088249A (zh) |
| CN (1) | CN1251758A (zh) |
| AP (1) | AP9901534A0 (zh) |
| AR (1) | AR016481A1 (zh) |
| AU (1) | AU753478B2 (zh) |
| BG (1) | BG103396A (zh) |
| BR (1) | BR9902086A (zh) |
| CA (1) | CA2272042A1 (zh) |
| CO (1) | CO5060503A1 (zh) |
| DZ (1) | DZ2786A1 (zh) |
| EA (1) | EA002830B1 (zh) |
| GT (1) | GT199900061A (zh) |
| HN (1) | HN1999000066A (zh) |
| HR (1) | HRP990144A2 (zh) |
| HU (1) | HUP9901606A2 (zh) |
| ID (1) | ID23299A (zh) |
| IS (1) | IS5046A (zh) |
| MA (1) | MA26629A1 (zh) |
| NO (1) | NO992339L (zh) |
| NZ (1) | NZ335772A (zh) |
| OA (1) | OA11040A (zh) |
| PA (1) | PA8472901A1 (zh) |
| PE (1) | PE20000546A1 (zh) |
| PL (1) | PL333118A1 (zh) |
| SG (1) | SG79255A1 (zh) |
| SK (1) | SK61599A3 (zh) |
| TR (1) | TR199901077A3 (zh) |
| YU (1) | YU21999A (zh) |
| ZA (1) | ZA993338B (zh) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105769887A (zh) * | 2014-12-23 | 2016-07-20 | 上海星泰医药科技有限公司 | 一种复方果糖二磷酸钠果糖口崩片及其制备方法 |
| CN114246835A (zh) * | 2022-01-05 | 2022-03-29 | 河北龙海药业有限公司 | 一种枸橼酸西地那非口腔崩解片的制备方法 |
Families Citing this family (43)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6743443B1 (en) * | 1998-10-05 | 2004-06-01 | Eisai Co., Ltd. | Tablets immediately disintegrating in the oral cavity |
| AU3724400A (en) * | 1999-03-08 | 2000-09-28 | Merck & Co., Inc. | Methods and compositions for treating erectile dysfunction |
| AU3744800A (en) * | 1999-03-16 | 2000-10-04 | Pentech Pharmaceuticals, Inc. | Controlled release of sildenafil delivered by sublingual or buccal administration |
| WO2000057857A1 (en) * | 1999-03-25 | 2000-10-05 | Yuhan Corporation | Rapidly disintegrable tablet for oral administration |
| KR100344198B1 (ko) * | 1999-10-08 | 2002-07-19 | 일양약품주식회사 | 실데나필 시트레이트의 속효제형 |
| US7501409B2 (en) * | 2000-09-06 | 2009-03-10 | Mitsubishi Tanabe Pharma Corporation | Preparations for oral administration |
| US6733781B2 (en) * | 2000-12-06 | 2004-05-11 | Wyeth | Fast dissolving tablet |
| IN192750B (zh) * | 2000-12-15 | 2004-05-15 | Ranbaxy Lab Ltd | |
| US6544552B2 (en) * | 2001-01-11 | 2003-04-08 | Particle And Coating Technologies, Inc. | Method of producing porous tablets with improved dissolution properties |
| EP1226818A1 (en) * | 2001-01-26 | 2002-07-31 | Pfizer Products Inc. | Pharmaceutical dosage forms with enhanced cohesive and compressibility properties |
| DE50209015D1 (de) * | 2001-05-09 | 2007-02-01 | Bayer Healthcare Ag | NEUE VERWENDUNG VON 2-Ä2-Ethoxy-5-(4-methyl-piperazin-1-sulfonyl)-phenylÜ-5-methyl-7-propyl-3H-imidazoÄ5,1-fÜÄ1,2,4Ütriazin-4-on |
| LV12978B (en) * | 2001-09-07 | 2003-05-20 | Ivars Kalvins | Pharmaceutical composition |
| JPWO2003028706A1 (ja) * | 2001-09-28 | 2005-01-13 | 株式会社三和化学研究所 | 有核型速溶崩壊性成型品 |
| US7118765B2 (en) | 2001-12-17 | 2006-10-10 | Spi Pharma, Inc. | Co-processed carbohydrate system as a quick-dissolve matrix for solid dosage forms |
| DE10232113A1 (de) * | 2002-07-16 | 2004-01-29 | Bayer Ag | Vardenafil Hydrochlorid Trihydrat enthaltende Arzneimittel |
| SE0202365D0 (sv) * | 2002-08-05 | 2002-08-05 | Pharmacia Ab | New formulation and use thereof |
| WO2004073729A1 (ja) | 2003-02-21 | 2004-09-02 | Translational Research Ltd. | 薬物の経鼻投与用組成物 |
| EP1607117A4 (en) | 2003-03-27 | 2007-10-24 | Bioactis Ltd | APPLICATOR FOR POWDER MEDICATION IN THE NOSE CAVE |
| US20050042177A1 (en) * | 2003-07-23 | 2005-02-24 | Elan Pharma International Ltd. | Novel compositions of sildenafil free base |
| US7670624B2 (en) | 2004-01-29 | 2010-03-02 | Astella Pharma Inc. | Gastrointestinal-specific multiple drug release system |
| DE102004023069A1 (de) * | 2004-05-11 | 2005-12-08 | Bayer Healthcare Ag | Neue Darreichungsformen des PDE 5-Inhibitors Vardenafil |
| US8673360B2 (en) * | 2004-08-10 | 2014-03-18 | Shin Nippon Biomedical Laboratories, Ltd. | Compositions that enable rapid-acting and highly absorptive intranasal administration |
| DE102005001989A1 (de) * | 2005-01-15 | 2006-07-20 | Bayer Healthcare Ag | Intravenöse Formulierungen von PDE-Inhibitoren |
| DE102005009240A1 (de) | 2005-03-01 | 2006-09-07 | Bayer Healthcare Ag | Arzneiformen mit verbesserten pharmakokinetischen Eigenschaften |
| DE102005009241A1 (de) * | 2005-03-01 | 2006-09-07 | Bayer Healthcare Ag | Arzneiformen mit kontrollierter Bioverfügbarkeit |
| CA2612917A1 (en) * | 2005-06-23 | 2007-01-04 | Schering Corporation | Rapidly absorbing oral formulations of pde5 inhibitors |
| US20090186896A1 (en) * | 2005-09-29 | 2009-07-23 | Bayer Healthcare Ag | PDE Inhibitors and Combinations Thereof for the Treatment of Urological Disorders |
| WO2008078730A1 (ja) * | 2006-12-26 | 2008-07-03 | Translational Research, Ltd. | 経鼻投与用製剤 |
| BRPI0807281A2 (pt) * | 2007-02-12 | 2014-04-29 | Dmi Biosciences Inc | Reduzindo os efeitos colaterais de tramadol |
| EP2167057A1 (en) * | 2007-06-13 | 2010-03-31 | Bayer HealthCare AG | Pde inhibitors for the treatment of hearing impairment |
| FR2932682B1 (fr) * | 2008-06-23 | 2013-07-12 | Bionetwork | Nouvelles formes pharmaceutiques a effet rapide et les utilisations des compositions pharmaceutiques ainsi obtenus. |
| US8617588B2 (en) | 2009-03-09 | 2013-12-31 | Spi Pharma, Inc. | Highly compactable and durable direct compression excipients and excipient systems |
| DE102009016584A1 (de) | 2009-04-06 | 2010-10-07 | Ratiopharm Gmbh | Schmelztablette, enthaltend ein Sildenafil-Salz |
| EP2429495A4 (en) * | 2009-05-15 | 2014-01-22 | Shin Nippon Biomedical Lab Ltd | INTRANASAL PHARMACEUTICAL COMPOSITIONS WITH ENHANCED PHARMACOKINETICS |
| US8827946B2 (en) * | 2009-07-31 | 2014-09-09 | Shin Nippon Biomedical Laboratories, Ltd. | Intranasal granisetron and nasal applicator |
| WO2011030351A2 (en) | 2009-09-03 | 2011-03-17 | Rubicon Research Private Limited | Taste - masked pharmaceutical compositions |
| EP2338474A1 (de) * | 2009-12-23 | 2011-06-29 | Ratiopharm GmbH | Oral dispersible Tablette enthaltend kompaktierte Sildenafil-Base |
| DE102010024866A1 (de) * | 2010-06-24 | 2011-12-29 | Pharmatech Gmbh | Formulierung zur Geschmacksmaskierung |
| CN103402504B (zh) * | 2011-02-11 | 2015-10-14 | 西梯茜生命工学股份有限公司 | 包含西地那非游离碱的膜制剂及其生产方法 |
| KR101418406B1 (ko) * | 2011-08-24 | 2014-07-10 | 한미약품 주식회사 | 실데나필 유리 염기를 포함하는 구강 붕해정 |
| MX366768B (es) * | 2011-12-08 | 2019-07-17 | Laboratorios Liomont S A De C V | Tableta orodispersable de sildenafil y metodo para preparar la misma. |
| KR102239291B1 (ko) | 2013-06-28 | 2021-04-14 | 한미약품 주식회사 | 타다라필 또는 이의 약학적으로 허용가능한 염을 포함하는 저작정 제제 |
| US11744967B2 (en) | 2017-09-26 | 2023-09-05 | Shin Nippon Biomedical Laboratories, Ltd. | Intranasal delivery devices |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2246013A1 (de) * | 1972-09-20 | 1974-03-28 | Boehringer Mannheim Gmbh | Verfahren zur herstellung von poroesen tabletten |
| US5624677A (en) * | 1995-06-13 | 1997-04-29 | Pentech Pharmaceuticals, Inc. | Controlled release of drugs delivered by sublingual or buccal administration |
| DE19532142A1 (de) * | 1995-08-31 | 1997-03-06 | Siemens Ag | Verfahren und Vorrichtung zur Regelung eines vierdimensionalen Vektors einer Strecke mittels eines wertediskreten Stellgliedes mit begrenzter Schaltfrequenz |
| GB9523752D0 (en) * | 1995-11-21 | 1996-01-24 | Pfizer Ltd | Pharmaceutical formulations |
| WO1998053819A1 (fr) * | 1997-05-29 | 1998-12-03 | Mochida Pharmaceutical Co., Ltd. | Agent therapeutique destine a traiter l'anerection |
| TW542719B (en) * | 1998-02-23 | 2003-07-21 | Pfizer Res & Dev | Method of treating impotence due to spinal cord injury |
| US6124461A (en) * | 1998-05-26 | 2000-09-26 | Saint Louis University, Health Services Center, Research Administration | Compounds, compositions, and methods for treating erectile dysfunction |
| AU3744800A (en) * | 1999-03-16 | 2000-10-04 | Pentech Pharmaceuticals, Inc. | Controlled release of sildenafil delivered by sublingual or buccal administration |
-
1999
- 1999-04-23 GT GT199900061A patent/GT199900061A/es unknown
- 1999-04-30 OA OA9900091A patent/OA11040A/en unknown
- 1999-05-06 SK SK615-99A patent/SK61599A3/sk unknown
- 1999-05-06 EP EP99303559A patent/EP0960621A3/en not_active Withdrawn
- 1999-05-07 IS IS5046A patent/IS5046A/is unknown
- 1999-05-10 HN HN1999000066A patent/HN1999000066A/es unknown
- 1999-05-10 PE PE1999000385A patent/PE20000546A1/es not_active Application Discontinuation
- 1999-05-12 BG BG103396A patent/BG103396A/bg unknown
- 1999-05-12 SG SG9902427A patent/SG79255A1/en unknown
- 1999-05-12 MA MA25577A patent/MA26629A1/fr unknown
- 1999-05-12 DZ DZ990086A patent/DZ2786A1/xx active
- 1999-05-13 KR KR1019990017127A patent/KR19990088249A/ko not_active Application Discontinuation
- 1999-05-13 HR HR60/085,646A patent/HRP990144A2/hr not_active Application Discontinuation
- 1999-05-13 YU YU21999A patent/YU21999A/sh unknown
- 1999-05-13 AR ARP990102274A patent/AR016481A1/es not_active Application Discontinuation
- 1999-05-13 CA CA002272042A patent/CA2272042A1/en not_active Abandoned
- 1999-05-13 EA EA199900373A patent/EA002830B1/ru not_active IP Right Cessation
- 1999-05-13 AU AU28126/99A patent/AU753478B2/en not_active Ceased
- 1999-05-13 AP APAP/P/1999/001534A patent/AP9901534A0/en unknown
- 1999-05-14 NZ NZ335772A patent/NZ335772A/xx unknown
- 1999-05-14 US US09/311,960 patent/US20020002172A1/en not_active Abandoned
- 1999-05-14 CN CN99106617A patent/CN1251758A/zh active Pending
- 1999-05-14 ZA ZA9903338A patent/ZA993338B/xx unknown
- 1999-05-14 HU HU9901606A patent/HUP9901606A2/hu unknown
- 1999-05-14 NO NO992339A patent/NO992339L/no not_active Application Discontinuation
- 1999-05-14 PA PA19998472901A patent/PA8472901A1/es unknown
- 1999-05-14 PL PL99333118A patent/PL333118A1/xx unknown
- 1999-05-14 TR TR1999/01077A patent/TR199901077A3/tr unknown
- 1999-05-14 BR BR9902086-6A patent/BR9902086A/pt not_active IP Right Cessation
- 1999-05-14 ID IDP990444D patent/ID23299A/id unknown
- 1999-05-17 JP JP11135193A patent/JPH11349483A/ja active Pending
- 1999-05-18 CO CO99030493A patent/CO5060503A1/es unknown
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105769887A (zh) * | 2014-12-23 | 2016-07-20 | 上海星泰医药科技有限公司 | 一种复方果糖二磷酸钠果糖口崩片及其制备方法 |
| CN105769887B (zh) * | 2014-12-23 | 2019-04-30 | 上海复星星泰医药科技有限公司 | 一种复方果糖二磷酸钠果糖口崩片及其制备方法 |
| CN114246835A (zh) * | 2022-01-05 | 2022-03-29 | 河北龙海药业有限公司 | 一种枸橼酸西地那非口腔崩解片的制备方法 |
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN1251758A (zh) | 口服崩解的药物制剂 | |
| ES2399810T3 (es) | Forma de dosificación farmacéutica sólida que comprende una dispersión sólida de ritonavir y lopinavir | |
| RU2193879C1 (ru) | Фармацевтическая композиция для лечения острых нарушений | |
| EP0804170B1 (en) | Method for making freeze dried drug dosage forms | |
| KR100843001B1 (ko) | 구강점막 부착형 필름제제 | |
| RU2376983C2 (ru) | Гастроретентивные композиции и способ их изготовления | |
| JP4439499B2 (ja) | アムロジピン含有粒子およびそれからなる口腔内崩壊錠 | |
| US20020119196A1 (en) | Texture masked particles containing an active ingredient | |
| EP1283703A1 (en) | Rapidly disintegrating tablet and process for the manufacture thereof | |
| JP2013511565A (ja) | フィルム様医薬剤形 | |
| CA2121038C (en) | Oral preparation for release in lower digestive tracts | |
| JPH04346930A (ja) | 安定なアスピリン腸溶錠 | |
| KR101046789B1 (ko) | 안정성이 개선된 암로디핀 속붕해성 정제 및 그의 제조방법 | |
| KR100675081B1 (ko) | 아세틸시스테인 함유 경구용 제제 | |
| KR100503949B1 (ko) | 염산 온단세트론의 쓴맛을 효과적으로 은폐한 경구용 구강속붕해정 조성물 | |
| TW200826962A (en) | Oral solid composition masking bitterness | |
| KR102209104B1 (ko) | 멜록시캄을 포함하는 구강붕해필름 제조방법 및 이에 의해 제조된 멜록시캄을 포함하는 구강붕해필름 | |
| JP5241681B2 (ja) | アムロジピン含有粒子およびそれからなる口腔内崩壊錠 | |
| CN1931168A (zh) | 盐酸地芬尼多口腔崩解片及其制备工艺 | |
| CN113952312A (zh) | 经口腔粘膜吸收的赛洛多辛药物 | |
| CZ159199A3 (cs) | Farmaceutický přípravek rozpadající se v ústech a způsob léčení sexuální dysfunkce | |
| KR20030027422A (ko) | 쓴맛의 은폐효과가 우수한 세푸록심 아세틸 약제 조성물과그 제조방법 | |
| KR20080071286A (ko) | 암로디핀 함유 입자 및 그것을 포함하는 구강 내 붕괴정 | |
| MXPA00006125A (en) | Flash-melt oral dosage formulation |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C06 | Publication | ||
| PB01 | Publication | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication | ||
| REG | Reference to a national code |
Ref country code: HK Ref legal event code: WD Ref document number: 1026634 Country of ref document: HK |