CA2482114C - Solid dosage form comprising caffeine - Google Patents
Solid dosage form comprising caffeine Download PDFInfo
- Publication number
- CA2482114C CA2482114C CA2482114A CA2482114A CA2482114C CA 2482114 C CA2482114 C CA 2482114C CA 2482114 A CA2482114 A CA 2482114A CA 2482114 A CA2482114 A CA 2482114A CA 2482114 C CA2482114 C CA 2482114C
- Authority
- CA
- Canada
- Prior art keywords
- caffeine
- dosage form
- cephalagic
- particle size
- microns
- 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 - Fee Related
Links
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 title claims abstract description 105
- 229960001948 caffeine Drugs 0.000 title claims abstract description 53
- LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 title claims abstract description 51
- VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 title claims abstract description 51
- 239000007909 solid dosage form Substances 0.000 title description 3
- 239000002245 particle Substances 0.000 claims abstract description 32
- 239000002552 dosage form Substances 0.000 claims abstract description 30
- 238000000034 method Methods 0.000 claims abstract description 10
- 239000007787 solid Substances 0.000 claims abstract description 6
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 claims description 21
- 239000000203 mixture Substances 0.000 claims description 17
- 238000005469 granulation Methods 0.000 claims description 10
- 230000003179 granulation Effects 0.000 claims description 10
- 229960005489 paracetamol Drugs 0.000 claims description 6
- 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 5
- 229960001680 ibuprofen Drugs 0.000 claims description 5
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 claims description 5
- SOYKEARSMXGVTM-UHFFFAOYSA-N chlorphenamine Chemical compound C=1C=CC=NC=1C(CCN(C)C)C1=CC=C(Cl)C=C1 SOYKEARSMXGVTM-UHFFFAOYSA-N 0.000 claims description 4
- 229960003291 chlorphenamine Drugs 0.000 claims description 4
- 229960000520 diphenhydramine Drugs 0.000 claims description 4
- ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical compound C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 claims description 4
- DKYWVDODHFEZIM-UHFFFAOYSA-N ketoprofen Chemical compound OC(=O)C(C)C1=CC=CC(C(=O)C=2C=CC=CC=2)=C1 DKYWVDODHFEZIM-UHFFFAOYSA-N 0.000 claims description 4
- 229960000991 ketoprofen Drugs 0.000 claims description 4
- 238000002156 mixing Methods 0.000 claims description 4
- 229940035676 analgesics Drugs 0.000 claims description 3
- 239000000730 antalgic agent Substances 0.000 claims description 3
- 239000000739 antihistaminic agent Substances 0.000 claims description 3
- 239000007891 compressed tablet Substances 0.000 claims description 3
- 229940125715 antihistaminic agent Drugs 0.000 claims description 2
- 239000000850 decongestant Substances 0.000 claims description 2
- 229940124581 decongestants Drugs 0.000 claims description 2
- 238000004090 dissolution Methods 0.000 abstract description 8
- 238000007907 direct compression Methods 0.000 abstract description 4
- 208000029618 autoimmune pulmonary alveolar proteinosis Diseases 0.000 description 9
- 239000007894 caplet 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
- 239000003826 tablet Substances 0.000 description 5
- 239000004480 active ingredient Substances 0.000 description 4
- 230000000202 analgesic effect Effects 0.000 description 4
- 239000004615 ingredient Substances 0.000 description 4
- 206010019233 Headaches Diseases 0.000 description 3
- 229920002472 Starch Polymers 0.000 description 3
- 231100000869 headache Toxicity 0.000 description 3
- 235000019359 magnesium stearate Nutrition 0.000 description 3
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 3
- 229920003109 sodium starch glycolate Polymers 0.000 description 3
- 239000008109 sodium starch glycolate Substances 0.000 description 3
- 229940079832 sodium starch glycolate Drugs 0.000 description 3
- 239000008107 starch Substances 0.000 description 3
- 229940032147 starch Drugs 0.000 description 3
- 235000019698 starch Nutrition 0.000 description 3
- 238000005550 wet granulation Methods 0.000 description 3
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 2
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 2
- 229920000881 Modified starch Polymers 0.000 description 2
- 235000021355 Stearic acid Nutrition 0.000 description 2
- -1 acidulants Substances 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 239000007884 disintegrant Substances 0.000 description 2
- 229940085392 excedrin Drugs 0.000 description 2
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 2
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 2
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 2
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 2
- 239000008108 microcrystalline cellulose Substances 0.000 description 2
- 229940016286 microcrystalline cellulose Drugs 0.000 description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 239000008117 stearic acid Substances 0.000 description 2
- TVYLLZQTGLZFBW-ZBFHGGJFSA-N (R,R)-tramadol Chemical compound COC1=CC=CC([C@]2(O)[C@H](CCCC2)CN(C)C)=C1 TVYLLZQTGLZFBW-ZBFHGGJFSA-N 0.000 description 1
- WBZFUFAFFUEMEI-UHFFFAOYSA-M Acesulfame k Chemical compound [K+].CC1=CC(=O)[N-]S(=O)(=O)O1 WBZFUFAFFUEMEI-UHFFFAOYSA-M 0.000 description 1
- 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 1
- 108010011485 Aspartame Proteins 0.000 description 1
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
- 229920002785 Croscarmellose sodium Polymers 0.000 description 1
- 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 description 1
- 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 1
- 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 description 1
- 239000004386 Erythritol Substances 0.000 description 1
- UNXHWFMMPAWVPI-UHFFFAOYSA-N Erythritol Natural products OCC(O)C(O)CO UNXHWFMMPAWVPI-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 208000019695 Migraine disease Diseases 0.000 description 1
- 239000004368 Modified starch Substances 0.000 description 1
- 206010039897 Sedation Diseases 0.000 description 1
- 239000004376 Sucralose Substances 0.000 description 1
- 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 1
- 229930006000 Sucrose Natural products 0.000 description 1
- GUGOEEXESWIERI-UHFFFAOYSA-N Terfenadine Chemical compound C1=CC(C(C)(C)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 GUGOEEXESWIERI-UHFFFAOYSA-N 0.000 description 1
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
- 235000010358 acesulfame potassium Nutrition 0.000 description 1
- 229960004998 acesulfame potassium Drugs 0.000 description 1
- 239000000619 acesulfame-K Substances 0.000 description 1
- 229960001138 acetylsalicylic acid Drugs 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 230000001387 anti-histamine Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 239000000605 aspartame Substances 0.000 description 1
- 235000010357 aspartame Nutrition 0.000 description 1
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 1
- 229960003438 aspartame Drugs 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 239000004359 castor oil Substances 0.000 description 1
- 235000019438 castor oil Nutrition 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- HCFDWZZGGLSKEP-UHFFFAOYSA-N doxylamine Chemical compound C=1C=CC=NC=1C(C)(OCCN(C)C)C1=CC=CC=C1 HCFDWZZGGLSKEP-UHFFFAOYSA-N 0.000 description 1
- 229960005178 doxylamine Drugs 0.000 description 1
- 239000002706 dry binder Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 235000019414 erythritol Nutrition 0.000 description 1
- UNXHWFMMPAWVPI-ZXZARUISSA-N erythritol Chemical compound OC[C@H](O)[C@H](O)CO UNXHWFMMPAWVPI-ZXZARUISSA-N 0.000 description 1
- 229940009714 erythritol Drugs 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 229960001375 lactose Drugs 0.000 description 1
- 239000000845 maltitol Substances 0.000 description 1
- 235000010449 maltitol Nutrition 0.000 description 1
- VQHSOMBJVWLPSR-WUJBLJFYSA-N maltitol Chemical compound OC[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O VQHSOMBJVWLPSR-WUJBLJFYSA-N 0.000 description 1
- 229940035436 maltitol Drugs 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 229960001855 mannitol Drugs 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
- 235000019426 modified starch Nutrition 0.000 description 1
- 230000031990 negative regulation of inflammatory response Effects 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 229920003124 powdered cellulose Polymers 0.000 description 1
- 235000019814 powdered cellulose Nutrition 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 230000036280 sedation Effects 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 229960002920 sorbitol Drugs 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 235000019408 sucralose Nutrition 0.000 description 1
- BAQAVOSOZGMPRM-QBMZZYIRSA-N sucralose Chemical compound O[C@@H]1[C@@H](O)[C@@H](Cl)[C@@H](CO)O[C@@H]1O[C@@]1(CCl)[C@@H](O)[C@H](O)[C@@H](CCl)O1 BAQAVOSOZGMPRM-QBMZZYIRSA-N 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 229960004793 sucrose Drugs 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 229960004380 tramadol Drugs 0.000 description 1
- TVYLLZQTGLZFBW-GOEBONIOSA-N tramadol Natural products COC1=CC=CC([C@@]2(O)[C@@H](CCCC2)CN(C)C)=C1 TVYLLZQTGLZFBW-GOEBONIOSA-N 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000012178 vegetable wax Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 230000004584 weight gain Effects 0.000 description 1
- 235000019786 weight gain Nutrition 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- 235000010447 xylitol Nutrition 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
- 229960002675 xylitol Drugs 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—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
-
- 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
- A61K31/52—Purines, e.g. adenine
-
- 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
- A61K31/52—Purines, e.g. adenine
- A61K31/522—Purines, e.g. adenine having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
-
- 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
- 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
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
Landscapes
- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- Neurosurgery (AREA)
- General Chemical & Material Sciences (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pain & Pain Management (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
A solid pharmaceutical dosage form comprising caffeine and a cephalagic is provided. The caffeine is in the form of uncoated particles having an average particle size of about 70 to 600 microns. The dosage form may be made by direct compression methods, and advantageously provides fast dissolution of the caffeine.
Description
SOLID DOSAGE FORM COMPRISING CAFFEINE
The present invention relates to a solid pharmaceutical dosage form comprising caffeine and a cephalagic, such as an analgesic ~r an NSAID. The caffeine is in the form of uncoated-particles having an average particle size of about 70 to 600 microns. The dosage form may be made by direct compression methods, and advantageously provides fast dissolution of the caffeine.
Back round of the Invention The use of caffeine in combination with other active ingredients in pharmaceutical dosage forms is known. For example; Canadian Patent No.
1,336;687 discloses a process for preparing tablets containing ibuprofen, acetaminophen (APAP), and caffeine. The tablets are made by first preparing wet granulations of each ingredient, combining the three granulations into a mixture, and tabletting the mixture. This patent teaches that separate wet granulation of the ingredients is necessary and preferred over direct compression of the three active ingredients together.
U.S. Patent No. 4,943,565 relates to an analgesic tablet containing aspirin, APAP, caffeine and hydroxypropyl cellulose. The caffeine was cogranulated with the other active ingredients using hydroxypropyl cellulose.
U.S. Patent No. 4,486,436 relates to compositions comprising caffeine together with analgesics andlor non-steroidal anti-inflammatory drugs (NSAID's).
The '436 patent discloses that caffeine in anhydrous powder form, or any salt or derivative of caffeine or any compounded mixture thereof which is non-toxic, pharmaceutically acceptable, and capable of hastening and enhancing an analgesic or anti-inflammatory response when employed may be used.
Applicants have now discovered that when caffeine of a certain type is employed in dosage forms, the caffeine unexpectedly dissolves from the dosage form faster. In particular, dosage forms comprising caffeine in the form of uncoated particles having an average particle size of about 70-to 60U microns provide fast caffeine dissolution rates. Typically, at least 95 °~o of the caffeine dissolves in less than 5 minutes; when measured by the United States Pharmacopoeia (USP), Type II
Apparatus (Paddles) set at 50 rpm.
Summary of the Invention The invention provides a solid pharmaceutical dosage form comprising caffeine and a cephalagic, wherein said caffeine is in the form of uncoated particles having an average particle size of about 74 to 600 microns.
The invention also provides a process for making a solid, pharmaceutical dosage form, which comprises dry blending caffeine and a cephalagic into a blend, wherein said caffeine is in the form of uncoated particles having an average particle size of about 70 to 600 microns, and compressing the blend.
Detailed Description of the Invention The dosage form comprises caffeine and one or more cephalagics. The cephalagic may be selected for example from analgesics, NSAID's, decongestants, antihistamines, and other agents known to treat headache and headache-related disorders. In one embodiment, the cephalagic is an analgesic selected from acetaminophen (APAP) and tramadol. In another embodiment; the cephalagic is an NSA1D selected from ibuprofen and ketoprofen. In a further embodiment, the cephalagic is an antihistamine selected from diphenhydramine, chlorpheniramine and doxcylamine. Preferably, the cephalagic is selected from the group consisting of acetaminophen, ibuprofen, ketoprofen, chlorpheniramine, diphenhydramine and doxylamine.
In one embodiment, the cephalagic is in the form of a granulation. The average particle size of such granulation is preferably in the range of about 100 to about 400 microns. This particle size range allows for adequate flow during processing and content uniformity.
The amount of caffeine used is typically in the range of about 5 mg to about 400 mg, preferably about 15 mg to about 200 mg per unit dose. The amount of cephalagic such as acetaminophen is typically in the range of about 1 mg to about 750 mg, preferably about 2 mg to about 500 mg per unit dose.
The caffeine is in the form of uncoated, ungranulated, larger particles ("granular" in morphology) having an average particle size of about 70 to 600, preferably 180 to 500, more preferably 200 to 500, microns. This is critical to the invention. Applicants have discovered that use of uncoated, ungranulated caffeine of this relatively larger particle size results in faster dissolution rates than that of powdered caffeine, even when disintegrants are used with powdered caffeine as part of a wet granulation process. The surfaces of the caffeine particles according to the invention are substantially free, preferably free, of polymeric binders and coating materials. One commercially available form of such caffeine may be obtained from BASF under the designation anhydrous caffeine granular; 0.2/0.5.
The dosage form is solid. In one embodiment, the dosage form is a compressed tablet or caplet. The dosage form may also be uncoated or coated with conventional coating materials. The dosage form may comprise conventional additives and excipients useful with solid dosage forms, such as fillers, including water soluble compressible carbohydrates such as sucrose, mannitol, sorbitol, maltitol, xylitol, erythritol, lactose, andmixtures thereof; conventional dry binders including cellulose, cellulosic derivatives;-polyvinyl pyrrolidone, starch, modified starch, and mixtures thereof; sweeteners including aspartame, acesulfame potassium, sucralose, saccharin and mixtures thereof; disintegrants such as microcrystalline cellulose, starch, sodium starch glycolate, crosslinked'polyvinylpyrrolidone, crosslinked carboxymethylcellulose; and lubricants, such as magnesium stearate, stearic acid, talc, vegetable oils and waxes. The dosage form may also incorporate pharmaceutically acceptable adjuvants, including for example preservatives, flavors, acidulants, antioxidants, glidants, surfactants, and coloring agents.
In one embodiment of the invention, the dosage form comprises a directly compressed blend of caffeine in the form of uncoated particles having an average particle size of about 200 to 500 microns and APAP in the form of a granulation having an average particle size of 100 to 400 microns, along with a lubricant such as magnesium stearate or stearic acid.
Advantageously, the dosage form may be made by dry, direct compression methods. In particular, the dosage form may be made by dry blending caffeine in the form of uncoated particles having an average particle size of about 70 to 600 microns and a cephalagic into a blend, and compressing the blend.
Typically, at least 9S % of the caffeine dissolves from a dosage form of the invention in less than 5 minutes, when measured by USP Type II Apparatus (Paddles) at 50 rpm. This is unexpected in hat the caffeine used is of a relatively large particle size as compared to powdered caffeine, which has a typical average particle size of about 50 microns. At the same time, uncoated caffeine according to the invention has been found to meet the content uniformity required by USP standards with commonly used cephalagics having particle sizes of from about 100 to about 400 microns.
This is useful to achieve faster therapeutic action of the caffeine, which is desirable when treating symptoms such as headache, migraines, or in cases where side effects such as sedation are undesirable.
The following non-limiting example further illustrates the invention:
Example A dosage form according to the invention was made by blending the following ingredients in dry form. The blend was directly compressed into caplets using a Fette 3090 tablet press set at 200, 360 or 400 thousand tablets per hour (61 station): The compressed caplets (with an average hardness of 13 KN or KiloNewtons of force) were coated with a mixture of hydroxypropylmethyl cellulose (HPMC E-5) and castor oil to a 2% weight gain. The caffeine was in the form of uncoated particles having an average particle size of 300-400 microns, commercially available from BASF as anhydrous caffeine, 0.2/0.5.
Ingredient mg/caplet APAP granulation 600:00*
Caffeine 65.00 Microcrystalline cellulose:PH-10166.86 Sodium starch glycolate 3.70 Magnesium stearate 4.44 Total 740.00 *APAP granulation (per 600 mg): 40 mg starch, 500 mg APAP, 40 mg powdered cellulose, 10 mg sodium starchglycolate; and lU mg pregelatinized starch.
The caplets were tested for caffeine and APAP dissolution rates using USP, Type II Apparatus (Paddles) set at 50 rpm and 100 rpm. Commercially available EXCEDRIN product, made by wet granulating caffeine and APAP together and compressing into dosage forms; was also tested for dissolution. In addition, commercially available NODOSE product, containing 200 mg of caffeine as the sole active ingredient, was tested for dissolution at a 50 rpm paddle speed.
The present invention relates to a solid pharmaceutical dosage form comprising caffeine and a cephalagic, such as an analgesic ~r an NSAID. The caffeine is in the form of uncoated-particles having an average particle size of about 70 to 600 microns. The dosage form may be made by direct compression methods, and advantageously provides fast dissolution of the caffeine.
Back round of the Invention The use of caffeine in combination with other active ingredients in pharmaceutical dosage forms is known. For example; Canadian Patent No.
1,336;687 discloses a process for preparing tablets containing ibuprofen, acetaminophen (APAP), and caffeine. The tablets are made by first preparing wet granulations of each ingredient, combining the three granulations into a mixture, and tabletting the mixture. This patent teaches that separate wet granulation of the ingredients is necessary and preferred over direct compression of the three active ingredients together.
U.S. Patent No. 4,943,565 relates to an analgesic tablet containing aspirin, APAP, caffeine and hydroxypropyl cellulose. The caffeine was cogranulated with the other active ingredients using hydroxypropyl cellulose.
U.S. Patent No. 4,486,436 relates to compositions comprising caffeine together with analgesics andlor non-steroidal anti-inflammatory drugs (NSAID's).
The '436 patent discloses that caffeine in anhydrous powder form, or any salt or derivative of caffeine or any compounded mixture thereof which is non-toxic, pharmaceutically acceptable, and capable of hastening and enhancing an analgesic or anti-inflammatory response when employed may be used.
Applicants have now discovered that when caffeine of a certain type is employed in dosage forms, the caffeine unexpectedly dissolves from the dosage form faster. In particular, dosage forms comprising caffeine in the form of uncoated particles having an average particle size of about 70-to 60U microns provide fast caffeine dissolution rates. Typically, at least 95 °~o of the caffeine dissolves in less than 5 minutes; when measured by the United States Pharmacopoeia (USP), Type II
Apparatus (Paddles) set at 50 rpm.
Summary of the Invention The invention provides a solid pharmaceutical dosage form comprising caffeine and a cephalagic, wherein said caffeine is in the form of uncoated particles having an average particle size of about 74 to 600 microns.
The invention also provides a process for making a solid, pharmaceutical dosage form, which comprises dry blending caffeine and a cephalagic into a blend, wherein said caffeine is in the form of uncoated particles having an average particle size of about 70 to 600 microns, and compressing the blend.
Detailed Description of the Invention The dosage form comprises caffeine and one or more cephalagics. The cephalagic may be selected for example from analgesics, NSAID's, decongestants, antihistamines, and other agents known to treat headache and headache-related disorders. In one embodiment, the cephalagic is an analgesic selected from acetaminophen (APAP) and tramadol. In another embodiment; the cephalagic is an NSA1D selected from ibuprofen and ketoprofen. In a further embodiment, the cephalagic is an antihistamine selected from diphenhydramine, chlorpheniramine and doxcylamine. Preferably, the cephalagic is selected from the group consisting of acetaminophen, ibuprofen, ketoprofen, chlorpheniramine, diphenhydramine and doxylamine.
In one embodiment, the cephalagic is in the form of a granulation. The average particle size of such granulation is preferably in the range of about 100 to about 400 microns. This particle size range allows for adequate flow during processing and content uniformity.
The amount of caffeine used is typically in the range of about 5 mg to about 400 mg, preferably about 15 mg to about 200 mg per unit dose. The amount of cephalagic such as acetaminophen is typically in the range of about 1 mg to about 750 mg, preferably about 2 mg to about 500 mg per unit dose.
The caffeine is in the form of uncoated, ungranulated, larger particles ("granular" in morphology) having an average particle size of about 70 to 600, preferably 180 to 500, more preferably 200 to 500, microns. This is critical to the invention. Applicants have discovered that use of uncoated, ungranulated caffeine of this relatively larger particle size results in faster dissolution rates than that of powdered caffeine, even when disintegrants are used with powdered caffeine as part of a wet granulation process. The surfaces of the caffeine particles according to the invention are substantially free, preferably free, of polymeric binders and coating materials. One commercially available form of such caffeine may be obtained from BASF under the designation anhydrous caffeine granular; 0.2/0.5.
The dosage form is solid. In one embodiment, the dosage form is a compressed tablet or caplet. The dosage form may also be uncoated or coated with conventional coating materials. The dosage form may comprise conventional additives and excipients useful with solid dosage forms, such as fillers, including water soluble compressible carbohydrates such as sucrose, mannitol, sorbitol, maltitol, xylitol, erythritol, lactose, andmixtures thereof; conventional dry binders including cellulose, cellulosic derivatives;-polyvinyl pyrrolidone, starch, modified starch, and mixtures thereof; sweeteners including aspartame, acesulfame potassium, sucralose, saccharin and mixtures thereof; disintegrants such as microcrystalline cellulose, starch, sodium starch glycolate, crosslinked'polyvinylpyrrolidone, crosslinked carboxymethylcellulose; and lubricants, such as magnesium stearate, stearic acid, talc, vegetable oils and waxes. The dosage form may also incorporate pharmaceutically acceptable adjuvants, including for example preservatives, flavors, acidulants, antioxidants, glidants, surfactants, and coloring agents.
In one embodiment of the invention, the dosage form comprises a directly compressed blend of caffeine in the form of uncoated particles having an average particle size of about 200 to 500 microns and APAP in the form of a granulation having an average particle size of 100 to 400 microns, along with a lubricant such as magnesium stearate or stearic acid.
Advantageously, the dosage form may be made by dry, direct compression methods. In particular, the dosage form may be made by dry blending caffeine in the form of uncoated particles having an average particle size of about 70 to 600 microns and a cephalagic into a blend, and compressing the blend.
Typically, at least 9S % of the caffeine dissolves from a dosage form of the invention in less than 5 minutes, when measured by USP Type II Apparatus (Paddles) at 50 rpm. This is unexpected in hat the caffeine used is of a relatively large particle size as compared to powdered caffeine, which has a typical average particle size of about 50 microns. At the same time, uncoated caffeine according to the invention has been found to meet the content uniformity required by USP standards with commonly used cephalagics having particle sizes of from about 100 to about 400 microns.
This is useful to achieve faster therapeutic action of the caffeine, which is desirable when treating symptoms such as headache, migraines, or in cases where side effects such as sedation are undesirable.
The following non-limiting example further illustrates the invention:
Example A dosage form according to the invention was made by blending the following ingredients in dry form. The blend was directly compressed into caplets using a Fette 3090 tablet press set at 200, 360 or 400 thousand tablets per hour (61 station): The compressed caplets (with an average hardness of 13 KN or KiloNewtons of force) were coated with a mixture of hydroxypropylmethyl cellulose (HPMC E-5) and castor oil to a 2% weight gain. The caffeine was in the form of uncoated particles having an average particle size of 300-400 microns, commercially available from BASF as anhydrous caffeine, 0.2/0.5.
Ingredient mg/caplet APAP granulation 600:00*
Caffeine 65.00 Microcrystalline cellulose:PH-10166.86 Sodium starch glycolate 3.70 Magnesium stearate 4.44 Total 740.00 *APAP granulation (per 600 mg): 40 mg starch, 500 mg APAP, 40 mg powdered cellulose, 10 mg sodium starchglycolate; and lU mg pregelatinized starch.
The caplets were tested for caffeine and APAP dissolution rates using USP, Type II Apparatus (Paddles) set at 50 rpm and 100 rpm. Commercially available EXCEDRIN product, made by wet granulating caffeine and APAP together and compressing into dosage forms; was also tested for dissolution. In addition, commercially available NODOSE product, containing 200 mg of caffeine as the sole active ingredient, was tested for dissolution at a 50 rpm paddle speed.
The caplets according to the invention demonstrated a significantly faster rate of caffeine dissolution at earlier time points than both the EXCEDRIN and NODOSE
products. The average percent of caffeine released from the two formulations is given in the Table below.
~ m o r .
~
c~
o U
~
n y Q
Q '~a'o~'oooo Z
D
c d ~ ~ ~~o oo , U
a o a h o Q mm~ ~
c U
O
.C o N
O
N
C
fl.
t0 N
N
N~t~ ~rv ~ ooo oo .. ,-ia U
U
p_ ~ dW~ ~o Z Q
LLl U ~
li!tGc0Nr f0lO
ctSMI~O'~OO~
U
m o .~
a a oo oo n ~
.
Q
o ~ Ua~
~a o ' c ~ ~00 00 U
~OtnMO
c D
M
O
U
products. The average percent of caffeine released from the two formulations is given in the Table below.
~ m o r .
~
c~
o U
~
n y Q
Q '~a'o~'oooo Z
D
c d ~ ~ ~~o oo , U
a o a h o Q mm~ ~
c U
O
.C o N
O
N
C
fl.
t0 N
N
N~t~ ~rv ~ ooo oo .. ,-ia U
U
p_ ~ dW~ ~o Z Q
LLl U ~
li!tGc0Nr f0lO
ctSMI~O'~OO~
U
m o .~
a a oo oo n ~
.
Q
o ~ Ua~
~a o ' c ~ ~00 00 U
~OtnMO
c D
M
O
U
Claims (13)
1. A solid pharmaceutical, dosage form comprising caffeine and a cephalagic, wherein said caffeine is in the form of uncoated particles having an average particle size of about 70 to 600 microns.
2. The dosage form of claim 1, wherein the cephalagic is selected from analgesics, non-steroidal anti-inflammatory drugs, decongestants, and antihistamines.
3. The dosage form of claim 1, wherein the cephalagic is selected from the group consisting of acetaminophen, ibuprofen, ketoprofen, chlorpheniramine, diphenhydramine, and doxcylamine.
4. The dosage form of claim 1, wherein the cephalagic is in the form of a granulation.
5. The dosage form of claim 4, wherein the granulation has an average particle size of about 100 to 400 microns.
6. The dosage form of claim 1 in the form of a directly compressed tablet.
7. The dosage form of claim 1, wherein at least 95 % of the caffeine dissolves within 5 minutes, when measured by USP, Type II Apparatus (Paddles) set at 50 rpm.
8. A process for making a olid, pharmaceutical dosage form, which comprises dry blending caffeine and a cephalagic into a blend, wherein said caffeine is in the form of uncoated particles haying an average particle size of about 70 to 600 microns, and compressing the blend.
9. The process of claim 8, wherein the cephalagic is selected from the group consisting of acetaminophen, ibuprofen, ketoprofen, chlorpheniramine, diphenhydramine, and doxcylamine.
10. The process of claim 8, wherein the cephalagic is in the form of a granulation:
11. The process of claim 10, wherein the granulation has an average particle size of about 100 to 400 microns.
12. The process of claim 8, wherein at least 95 % of the caffeine in the compressed blend dissolves within 5 minutes, when measured by USP, Type II
Apparatus (Paddles) set at 50 rpm.
Apparatus (Paddles) set at 50 rpm.
13. A compressed tablet made by the process of claim 8.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US10/671,138 US20050065172A1 (en) | 2003-09-23 | 2003-09-23 | Solid dosage form comprising caffeine |
| US10/671,138 | 2003-09-23 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2482114A1 CA2482114A1 (en) | 2005-03-23 |
| CA2482114C true CA2482114C (en) | 2011-12-13 |
Family
ID=34194840
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2482114A Expired - Fee Related CA2482114C (en) | 2003-09-23 | 2004-09-21 | Solid dosage form comprising caffeine |
Country Status (11)
| Country | Link |
|---|---|
| US (1) | US20050065172A1 (en) |
| EP (1) | EP1518551B1 (en) |
| KR (1) | KR20050030157A (en) |
| CN (1) | CN100441224C (en) |
| AT (1) | ATE376827T1 (en) |
| CA (1) | CA2482114C (en) |
| DE (1) | DE602004009731T2 (en) |
| ES (1) | ES2295787T3 (en) |
| MX (1) | MXPA04009258A (en) |
| PL (1) | PL1518551T3 (en) |
| PT (1) | PT1518551E (en) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0525029D0 (en) * | 2005-12-08 | 2006-01-18 | Univ Hull | Receptor Antagonist |
| US20150209360A1 (en) * | 2014-01-30 | 2015-07-30 | Orbz, Llc | Oral caffeine delivery composition |
| US20210274828A1 (en) * | 2014-06-06 | 2021-09-09 | Nicholas J. Singer | Quick dissolve drinks and edibles and machine for manufacturing the same |
| AU2024293629A1 (en) * | 2023-07-07 | 2026-01-22 | Lyrus Life Sciences Pvt. Ltd. | Taste masked granule composition of caffeine and its process of preparation |
Family Cites Families (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1287431A (en) * | 1969-04-16 | 1972-08-31 | Aspro Nicholas Ltd | Improvements in pharmaceutical formulations |
| US4049803A (en) * | 1976-04-26 | 1977-09-20 | Bristol-Myers Company | Augmentation of blood levels of aspirin |
| US4486436A (en) * | 1982-07-22 | 1984-12-04 | Analgesic Associates | Analgesic and anti-inflammatory compositions comprising caffeine and methods of using same |
| US4420483A (en) * | 1982-07-22 | 1983-12-13 | Richardson-Vicks, Inc. | Analgesic and anti-inflammatory compositions comprising ibuprofen and methods of using same |
| SE457326B (en) * | 1986-02-14 | 1988-12-19 | Lejus Medical Ab | PROCEDURES FOR PREPARING A QUICK SUBSTANTIAL CANDLES CONTAINING BLA MICROCRISTALLIN CELLULOSA |
| US4943565A (en) * | 1986-09-15 | 1990-07-24 | Bristol-Myers Squibb Company | Analgesic tablet of aspirin and caffeine containing low-substituted hydroxypropyl cellulose |
| SG80535A1 (en) * | 1991-09-06 | 2001-05-22 | Mcneilab Inc | Composition comprising a tramadol material and acetaminophen and its use |
| ES2046097B1 (en) * | 1991-10-28 | 1994-09-01 | S A L V A T Lab Sa | PROCEDURE FOR PREPARING AN ANTIDESMENORRHEA COMPOSITION. |
| US5409709A (en) * | 1991-11-29 | 1995-04-25 | Lion Corporation | Antipyretic analgesic preparation containing ibuprofen |
| US6020002A (en) * | 1994-06-14 | 2000-02-01 | Fuisz Technologies Ltd. | Delivery of controlled-release system(s) |
| US5958453A (en) * | 1996-10-31 | 1999-09-28 | Takeda Chemical Industries, Ltd. | Solid pharmaceutical preparation with improved buccal disintegrability and/or dissolubility |
| JP2001508493A (en) * | 1998-01-13 | 2001-06-26 | ザ、プロクター、エンド、ギャンブル、カンパニー | Detergent granules with improved solubility |
| GB9816899D0 (en) * | 1998-08-05 | 1998-09-30 | Boots Co Plc | Therapeutic agents |
| DE19931708A1 (en) * | 1999-07-08 | 2001-01-18 | Bayer Ag | Process for the preparation of rapidly disintegrating solid pharmaceutical preparations |
-
2003
- 2003-09-23 US US10/671,138 patent/US20050065172A1/en not_active Abandoned
-
2004
- 2004-09-21 CA CA2482114A patent/CA2482114C/en not_active Expired - Fee Related
- 2004-09-22 EP EP04255750A patent/EP1518551B1/en not_active Expired - Lifetime
- 2004-09-22 PT PT04255750T patent/PT1518551E/en unknown
- 2004-09-22 AT AT04255750T patent/ATE376827T1/en not_active IP Right Cessation
- 2004-09-22 ES ES04255750T patent/ES2295787T3/en not_active Expired - Lifetime
- 2004-09-22 PL PL04255750T patent/PL1518551T3/en unknown
- 2004-09-22 DE DE602004009731T patent/DE602004009731T2/en not_active Expired - Lifetime
- 2004-09-23 KR KR1020040076642A patent/KR20050030157A/en not_active Withdrawn
- 2004-09-23 MX MXPA04009258A patent/MXPA04009258A/en active IP Right Grant
- 2004-09-23 CN CNB2004100826412A patent/CN100441224C/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| CA2482114A1 (en) | 2005-03-23 |
| ES2295787T3 (en) | 2008-04-16 |
| DE602004009731D1 (en) | 2007-12-13 |
| EP1518551B1 (en) | 2007-10-31 |
| PL1518551T3 (en) | 2008-03-31 |
| US20050065172A1 (en) | 2005-03-24 |
| ATE376827T1 (en) | 2007-11-15 |
| CN100441224C (en) | 2008-12-10 |
| MXPA04009258A (en) | 2005-07-05 |
| CN1616103A (en) | 2005-05-18 |
| PT1518551E (en) | 2007-12-06 |
| KR20050030157A (en) | 2005-03-29 |
| DE602004009731T2 (en) | 2008-08-28 |
| EP1518551A1 (en) | 2005-03-30 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US6797732B2 (en) | Pharmaceutical composition comprising entracapone, levodopa, and carbidopa | |
| EP0749308B1 (en) | Film coated tablet of paracetamol and domperidone | |
| RU2485947C2 (en) | Pharmaceutical compositions of entacapone, levodopa and carbidopa with improved bioavailability | |
| NO330270B1 (en) | Immediately dissolving pharmaceutical dosage form and process for forming granules | |
| WO2009151072A1 (en) | Tablet quickly disintegrating in the oral cavity and method for producing the same | |
| MX2012015091A (en) | Pharmaceutical compositions comprising 4-amino-5-fluoro-3-[6-(4-m ethylpiperazin-1-yl)-1h-benzimidazol-2-yl]-1h-quinolin-2-one lactate monohydrate. | |
| WO2008072534A1 (en) | Solid medicinal preparation containing mannitol or lactose | |
| JPH1017497A (en) | Sustained release pharmaceutical preparation and its production | |
| KR20000075897A (en) | Swallow tablet comprising paracetamol | |
| WO2009150665A1 (en) | Orally disintegrating pharmaceutical compositions of escitalopram and salts thereof | |
| US20060222703A1 (en) | Pharmaceutical composition and preparation method thereof | |
| CA2482114C (en) | Solid dosage form comprising caffeine | |
| JPH08310969A (en) | Solid pharmaceutical composition and method for producing the same | |
| JP4519444B2 (en) | Orally disintegrating tablets | |
| JP4848140B2 (en) | Stabilized solid formulations containing vitamin Cs | |
| JP2000063269A (en) | Solid preparation | |
| WO2005120463A1 (en) | Rapidly disintegrating tablets of risperidone | |
| EP0975337B1 (en) | Fast release compressed tablet of flurbiprofen | |
| JP2012046454A (en) | Tablet for internal use and method for producing the same | |
| WO2005077341A1 (en) | Orally disintegrating pharmaceutical compositions of ondansetron | |
| JP2025023577A (en) | Solid preparations | |
| JP2003300874A (en) | Solid preparation containing pseudoephedrine hydrochloride | |
| JP2022087085A (en) | Solid preparation containing ibuprofen | |
| WO2007113371A1 (en) | Pharmaceutical composition and preparation method thereof | |
| HK1010687B (en) | Film coated tablet of paracetamol and domperidone |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKLA | Lapsed |
Effective date: 20200921 |