EP2804594A1 - Formulierungen mit diclofenac als wirkstoff - Google Patents

Formulierungen mit diclofenac als wirkstoff

Info

Publication number: EP2804594A1
Authority: EP; European Patent Office
Prior art keywords: formulation; diclofenac; range; agent; effervescent
Prior art date: 2012-01-18
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 Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Withdrawn

Application number

EP13720143.0A

Other languages

English (en)

French (fr)

Inventor

Mahmut Bilgic

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Individual

Original Assignee

Individual

Priority date (The priority date 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 date listed.)

2012-01-18

Filing date

2013-01-18

Publication date

2014-11-26

2013-01-18 Application filed by Individual filed Critical Individual

2014-11-26 Publication of EP2804594A1 publication Critical patent/EP2804594A1/de

Status Withdrawn legal-status Critical Current

Links

239000000203 mixture Substances 0.000 title claims abstract description 140
238000009472 formulation Methods 0.000 title claims abstract description 109
DCOPUUMXTXDBNB-UHFFFAOYSA-N diclofenac Chemical compound OC(=O)CC1=CC=CC=C1NC1=C(Cl)C=CC=C1Cl DCOPUUMXTXDBNB-UHFFFAOYSA-N 0.000 title claims abstract description 84
229960001259 diclofenac Drugs 0.000 title claims abstract description 84
239000013543 active substance Substances 0.000 title claims description 36
230000000202 analgesic effect Effects 0.000 claims abstract description 6
230000003110 anti-inflammatory effect Effects 0.000 claims abstract description 6
230000001754 anti-pyretic effect Effects 0.000 claims abstract description 5
239000006172 buffering agent Substances 0.000 claims description 44
239000002253 acid Substances 0.000 claims description 22
230000002378 acidificating effect Effects 0.000 claims description 22
235000003599 food sweetener Nutrition 0.000 claims description 19
239000008194 pharmaceutical composition Substances 0.000 claims description 19
239000003765 sweetening agent Substances 0.000 claims description 19
239000003795 chemical substances by application Substances 0.000 claims description 11
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 9
239000000546 pharmaceutical excipient Substances 0.000 claims description 9
230000001105 regulatory effect Effects 0.000 claims description 9
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 8
238000005469 granulation Methods 0.000 claims description 8
230000003179 granulation Effects 0.000 claims description 8
239000002245 particle Substances 0.000 claims description 8
239000011230 binding agent Substances 0.000 claims description 7
239000007938 effervescent tablet Substances 0.000 claims description 7
239000000945 filler Substances 0.000 claims description 7
239000000314 lubricant Substances 0.000 claims description 7
239000002904 solvent Substances 0.000 claims description 7
239000000080 wetting agent Substances 0.000 claims description 7
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239000003826 tablet Substances 0.000 claims description 6
HRXKRNGNAMMEHJ-UHFFFAOYSA-K trisodium citrate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O HRXKRNGNAMMEHJ-UHFFFAOYSA-K 0.000 claims description 6
OROGSEYTTFOCAN-DNJOTXNNSA-N codeine Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC OROGSEYTTFOCAN-DNJOTXNNSA-N 0.000 claims description 5
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238000002360 preparation method Methods 0.000 claims description 4
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229910000021 magnesium carbonate Inorganic materials 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
229940091250 magnesium supplement Drugs 0.000 description 1
239000001630 malic acid Substances 0.000 description 1
235000011090 malic acid Nutrition 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
229940035034 maltodextrin Drugs 0.000 description 1
239000000594 mannitol Substances 0.000 description 1
235000010355 mannitol Nutrition 0.000 description 1
238000004519 manufacturing process Methods 0.000 description 1
229920000609 methyl cellulose Polymers 0.000 description 1
239000001923 methylcellulose Substances 0.000 description 1
235000010981 methylcellulose Nutrition 0.000 description 1
239000008108 microcrystalline cellulose Substances 0.000 description 1
229940016286 microcrystalline cellulose Drugs 0.000 description 1
235000019813 microcrystalline cellulose Nutrition 0.000 description 1
229940045641 monobasic sodium phosphate Drugs 0.000 description 1
229910000403 monosodium phosphate Inorganic materials 0.000 description 1
235000019799 monosodium phosphate Nutrition 0.000 description 1
235000011007 phosphoric acid Nutrition 0.000 description 1
229960000502 poloxamer Drugs 0.000 description 1
229920001983 poloxamer Polymers 0.000 description 1
229920001223 polyethylene glycol Polymers 0.000 description 1
-1 polyoxyethylene Polymers 0.000 description 1
229920002451 polyvinyl alcohol Polymers 0.000 description 1
235000019422 polyvinyl alcohol Nutrition 0.000 description 1
235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 1
229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 1
229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
239000004300 potassium benzoate Substances 0.000 description 1
235000010235 potassium benzoate Nutrition 0.000 description 1
229940103091 potassium benzoate Drugs 0.000 description 1
239000011736 potassium bicarbonate Substances 0.000 description 1
229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
235000015497 potassium bicarbonate Nutrition 0.000 description 1
239000001508 potassium citrate Substances 0.000 description 1
229960002635 potassium citrate Drugs 0.000 description 1
QEEAPRPFLLJWCF-UHFFFAOYSA-K potassium citrate (anhydrous) Chemical compound [K+].[K+].[K+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O QEEAPRPFLLJWCF-UHFFFAOYSA-K 0.000 description 1
235000011082 potassium citrates Nutrition 0.000 description 1
TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
235000011118 potassium hydroxide Nutrition 0.000 description 1
229940069328 povidone Drugs 0.000 description 1
235000019260 propionic acid Nutrition 0.000 description 1
IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
239000011734 sodium Substances 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
235000015424 sodium Nutrition 0.000 description 1
239000001632 sodium acetate Substances 0.000 description 1
235000017281 sodium acetate Nutrition 0.000 description 1
229960004249 sodium acetate Drugs 0.000 description 1
WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
239000004299 sodium benzoate Substances 0.000 description 1
235000010234 sodium benzoate Nutrition 0.000 description 1
229960001790 sodium citrate Drugs 0.000 description 1
AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
APSBXTVYXVQYAB-UHFFFAOYSA-M sodium docusate Chemical compound [Na+].CCCCC(CC)COC(=O)CC(S([O-])(=O)=O)C(=O)OCC(CC)CCCC APSBXTVYXVQYAB-UHFFFAOYSA-M 0.000 description 1
235000019333 sodium laurylsulphate Nutrition 0.000 description 1
229940045902 sodium stearyl fumarate Drugs 0.000 description 1
239000012453 solvate Substances 0.000 description 1
239000000600 sorbitol Substances 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch 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
229910021653 sulphate ion Inorganic materials 0.000 description 1
239000000829 suppository Substances 0.000 description 1
239000007939 sustained release tablet Substances 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
229940001496 tribasic sodium phosphate Drugs 0.000 description 1
RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 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
- A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
- A61K9/0007—Effervescent
- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/196—Carboxylic acids, e.g. valproic acid having an amino group the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/485—Morphinan derivatives, e.g. morphine, codeine
- 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
- A61K31/557—Eicosanoids, e.g. leukotrienes or prostaglandins
- A61K31/5575—Eicosanoids, e.g. leukotrienes or prostaglandins having a cyclopentane, e.g. prostaglandin E2, prostaglandin F2-alpha
- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
- A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca

Definitions

the present invention has analgesic, anti-inflammatory and antipyretic activity and relates to pharmaceutical formulations comprising diclofenac that shall be used in the treatment of mild, moderate and severe pain, arthralgia, fever, toothache, dysmenorrhea, toothache, myalgia, osteoarthritis, rheumatoid arthritis, backache.
Diclofenac was first disclosed in the application numbered US3558690.
Diclofenac and/or its pharmaceutically acceptable salts are analgesic, anti-inflammatory and anti-rheumatic drugs belonging to the group of non-steroidal anti-inflammatory drugs (NSAID).
NSAID non-steroidal anti-inflammatory drugs
Diclofenac is available in the forms of 25 mg and 50 mg dragee; 75 mg/3ml ampoule; 1%,2% and 3% gel; 100 mg capsule; 0.1% eye drop; 50 mg and 100 mg suppository; 75 mg and 100 mg sustained release tablet; 25 mg, 50 mg and 100 mg enterically coated tablet and 100 mg retard tablet on the market.
Diclofenac is a hygroscopic molecule and thus its water solubility is quite low. Therefore, it is observed that effervescent formulations comprising diclofenac disperse slowly when they contact with water and the active agent does not dissolve sufficiently owing to these characteristics of the active agent diclofenac. Due to this, sufficient amount of the active agent cannot be absorbed; the required bioavailability cannot be obtained. Consequently, an effective treatment cannot be provided. In other aspect, it is required that the solutions obtained by dissolving the formulations comprising diclofenac in water should have a pH value in water in the range of 4,1-5 according to the specifications.
the effervescent formulations comprising diclofenac comprise at least two buffering agents having acidic and basic characteristics along with effervescent acid and effervescent base and the ratio of the acidic buffering agent to the basic buffering agent is in the range of 70: 1 to 10: 1; they have high water solubility, bioavailability and therapeutic activity and they do not cause any stomach disturbances since the solution obtained during use of said formulations is in optimal pH range for the stomach.
the present invention relates to pharmaceutical formulations comprising diclofenac.
diclofenac effervescent formulations which comprise at least two buffering agents having acidic and basic characteristics along with effervescent acid and effervescent base and wherein the ratio of the acidic buffering agent to the basic buffering agent is in the range of 70:1 to 10:1, have high water solubility, bioavailability and therapeutic activity.
the inventors have seen that since the solution obtained during use of said formulations is in optimal pH range for the stomach, it does not cause stomach disturbances and an effective treatment is obtained.
the first aspect of the present invention is that the effervescent formulations comprising diclofenac comprise at least two acidic and basic buffering agents along with effervescent acid and effervescent base and the ratio of the acidic buffering agent to the basic buffering agent is in the range of 70:1 to 10: 1.
said formulation comprises diclofenac in the range of 0.1-10%, preferably in the range of 0.5-8%, more preferably in the range of 1- 5 % as the active agent.
Diclofenac comprised in the pharmaceutical formulations of the present invention is in the form of its pharmaceutically acceptable organic and inorganic salts, hydrates, solvates, esters, enantiomers, racemates or combinations thereof in terms of chemical structure; in free form, crystalline, amorphous forms or combinations thereof in terms of polymorphic structure.
the particle size of diclofenac active agent is another parameter affecting on the dissolution and bioavailability of the formulation.
the inventors have found that in the case that diclofenac used as active agent has average particle size in the range of 1-100 ⁇ , preferably 3-60 ⁇ ⁇ , more preferably 5-40 ⁇ , the obtained effervescent formulation dissolves rapidly and thus a high bioavailability is obtained.
the present invention relates to the pharmaceutical formulations wherein diclofenac which is used as active agent has average particle size in the range of 1-100 ⁇ , preferably 3-60 ⁇ , more preferably 5-40 ⁇ .
the present invention relates to the pharmaceutical formulations wherein the ratio of di 0 value of diclofenac to d 90 value of diclofenac is in the range of 1 : 1 to 1 :100, preferably in the range of 1 : 10 to 1 :75, and more preferably in the range of 1 :20 to 1 :60.
d 10 value used herein signifies that 10% of the said substance by volume has a particle size below the value stated with di 0 .
d 90 value used herein signifies that 90% of the said substance by volume has a particle size below the value stated with d 90.
the formulations of the present invention comprising diclofenac are in the form of effervescent tablet, granule or powder, preferably in effervescent tablet form.
the effervescent acid comprised in the formulation comprising diclofenac according to the present invention is less than 60%, preferably in the range of 10-59%, more preferably in the range of 20-40%.
the effervescent base in the formulation comprising diclofenac according to the present invention is more than 15%, preferably in the range of 15.1-58%, more preferably in the range of 20-55%
the effervescent acid in the formulation of the present invention can be selected from a group comprising acetic acid, citric acid, lactic acid, malic acid, phosphoric acid, propionic acid, tartaric acid and monosodium citrate or a combination thereof.
citric acid or monosodium citrate is used as the effervescent acid.
the effervescent base in the pharmaceutical formulations of the present invention can be selected from a group comprising sodium bicarbonate, sodium citrate dihydrate, sodium hydroxide or combinations thereof.
preferably sodium bicarbonate is used as the effervescent base.
the ratio of the basic buffering agent to the acidic buffering agent is in the range of 60.T to 20: 1, more preferably in the range of 55:l to 30:l .
the basic buffering agent can be selected from a group comprising potassium bicarbonate, potassium citrate, potassium hydroxide, sodium bicarbonate, sodium citrate dihydrate, sodium hydroxide or a combination thereof.
sodium carbonate is used as the basic buffering agent in the formulations of the present invention.
the acidic buffering agent used in the pharmaceutical formulations of the present invention can be selected from a group comprising sodium citrate, sodium acetate, dibasic sodium phosphate, tribasic sodium phosphate, monobasic sodium phosphate, sodium acid pyrophosphate and sodium acid sulphate or a combination thereof.
sodium citrate more preferably its sodium citrate dihydrate form is used as the acidic buffering agent in the formulations of the present invention.
the ratio of sodium carbonate: sodium citrate dihydrate is in the range of 70: 1 to 10:1, preferably in the range of 60: 1 to 20: 1, more preferably in the range of 55: 1 to 30: 1.
the inventors have also seen that the weight ratio of diclofenac active agent to buffering agents has an influence on the dissolution and homogeneity of the formulation. They have observed that when the ratio of diclofenac to the combination of the buffering agents is in the range of 1 : 10 to 9: 10, preferably 2:10 to 6: 10 by weight, homogeneous and rapidly dispersible effervescent formulations have been provided.
the present invention relates to the effervescent formulations wherein the ratio of diclofenac active agent to the combination of the buffering agents is in the range of 1 : 10 to 9:10, preferably 2:10 to 6: 10 by weight.
the formulations of the present invention can comprise at least one pharmaceutically acceptable excipient along with diclofenac, effervescent acid, effervescent base, basic buffering agent and acidic buffering agent.
the pharmaceutically acceptable excipients that can be used in the formulations of the present invention can be selected from lubricant, sweetener and/or taste regulating agent, wetting agent, filling agent, binder, solvent or combinations thereof.
composition comprising two different sweeteners is used as the sweetener and/or taste regulating agent.
the sweeteners used in the formulations of the present invention can be selected from a group comprising acesulfame potassium, aspartame, fructose, maltitol, xylitol, saccharine, sodium cyclamate, sucralose, sucrose.
the sweetener composition used as the sweetener and/or taste regulating agent is preferably composed of sodium cyclamate and aspartame.
the lubricant used in the formulations of the present invention can be selected from a group comprising calcium stearate, magnesium stearate, sodium stearyl fumarate, polyethylene glycol, PEG 6000, polyvinyl alcohol, adipic acid, potassium benzoate, sodium benzoate.
the wetting agent used in the formulations of the present invention can be selected from a group comprising benzalkonium chloride, poloxamer, docusate sodium, polyoxyethylene alkyl ester, sodium lauryl sulphate or combinations thereof.
the filling agent used in the formulations of the present invention can be selected from a group comprising D-manntiol, xylitol, microcrystalline cellulose, crospovidone, dibasic calcium phosphate anhydrous, lactose, starch, maltose, dextrin, maltodextrin, magnesium carbonate, talc and combinations thereof.
the binder used in the formulations of the present invention can be selected from a group comprising ethyl cellulose, gelatine, hydroxyethyl cellulose, hydroxymethyl cellulose, hydroxypropyl cellulose, hypromellose, magnesium aluminium silicate, methyl cellulose and povidone.
the solvent used in the formulations of the present invention can be selected from a group comprising sorbitol, propylene glycol, methanol, ethanol, isopropyl alcohol, mannitol, ethylene glycol, butyl alcohol, penthanol or combinations thereof.
the effervescent formulations comprising diclofenac of the present invention can optionally comprise a second active agent in addition to diclofenac.
the second active agent that can be used along with diclofenac in the formulations of the present invention can be selected from analgesic, antipyretic, myorelaxant, non-steroidal antiinflammatory, prostaglandin analogue, gastric proton pump inhibitor (PPI), opiate agonist agents or combinations thereof.
PPI gastric proton pump inhibitor
the diclofenac effervescent formulations of the present invention can preferably comprise an opiate agonist, more preferably codeine as the second active agent in addition to diclofenac.
the diclofenac effervescent formulations of the present invention can preferably comprise a myorelaxant, more preferably thiocolchicoside as the second active agent in addition to diclofenac.
the diclofenac effervescent formulations of the present invention can preferably comprise a prostaglandin analogue, more preferably misoprostol as the second active agent in addition to diclofenac.
the diclofenac effervescent formulations of the present invention can preferably comprise a gastric proton pump inhibitor (PPI), more preferably rabeprazole as the second active agent in addition to diclofenac.
PPI gastric proton pump inhibitor
the effervescent formulation comprising diclofenac which is prepared according to the production method of the present invention can comprise diclofenac in the range of 0.1-10%, effervescent acid in the range of 10-59%, effervescent base in the range of 15.1-58%, binder in the range of 0.01-3%, lubricant in the range of 1-10%, sweetener and/or taste regulating agent in the range of 0.2-5%, filling agent in the range of 2-15%, acidic buffering agent in the range of 0.05-2%, basic buffering agent in the range of 1-10%, wetting agent in the range of 0.01-2%, solvent in the range of 0.05-4% and flavouring agent in the range of 0.2-3% in proportion to total weight of unit amount.
Preparation of the pharmaceutical formulations of the present invention can be performed by a process which is composed of the steps of:
the pharmaceutical formulation of the present invention has analgesic, anti-inflammatory and antipyretic activity and it can be used in the treatment of the diseases such as mild, moderate and severe pain, arthralgia, fever, toothache, dysmenorrhea, toothache, myalgia, osteoarthritis, rheumatoid arthritis, backache.
EXAMPLE 1 Formulation and process for preparation of effervescent tablet comprising diclofenac
Diclofenac, the effervescent acid and the effervescent base are mixed to obtain the formulation that shall be used in the present invention.
the 1 st mixture is obtained by granulating said mixture with a granulation solution obtained by dissolving the wetting agent and the binder in the solvent and water.
the effervescent acid and the sweetener are mixed and said mixture is granulated with the granulation solution obtained by dissolving the acidic buffering agent in water.
the 2 nd mixture is obtained by adding the effervescent base, the basic buffering agent and the lubricant into the granules obtained.
EXAMPLE 2 Formulation and process for preparation of effervescent tablet comprising diclofenac and codeine
Diclofenac, codeine, the effervescent acid and the effervescent base are mixed to obtain the formulation that shall be used in the present invention.
the 1 st mixture is obtained by granulating said mixture with the granulation solution obtained by dissolving the wetting agent and the binder in the solvent and water.
the effervescent acid and the sweetener are mixed and said mixture is granulated with the granulation solution obtained by dissolving the acidic buffering agent in water.
the 2 nd mixture is obtained by adding the effervescent base, the basic buffering agent and the lubricant into the granules obtained.
the 1 st mixture, the 2 nd mixture, the filling agent and the flavouring agent are mixed and the final mixture obtained is compressed in tablet form.

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Veterinary Medicine (AREA)
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Bioinformatics & Cheminformatics (AREA)
Emergency Medicine (AREA)
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Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

EP13720143.0A 2012-01-18 2013-01-18 Formulierungen mit diclofenac als wirkstoff Withdrawn EP2804594A1 (de)

Applications Claiming Priority (4)

Application Number	Priority Date	Filing Date	Title
TR201200602		2012-01-18
TR201205008		2012-04-30
TR201205319		2012-05-08
PCT/TR2013/000034 WO2013109222A1 (en)	2012-01-18	2013-01-18	Formulations comprising diclofenac as the active agent

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Publication Number	Publication Date
EP2804594A1 true EP2804594A1 (de)	2014-11-26

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WO2013165327A1 (en) *	2012-04-30	2013-11-07	Mahmut Bilgic	Pharmaceutical formulations comprising thiocolchicoside

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US3558690A (en)	1965-04-08	1971-01-26	Gelgy Chemical Corp	Substituted derivatives of 2-anilinophenylacetic acids and a process of preparation
US5211957A (en) *	1988-03-25	1993-05-18	Ciba-Geigy Corporation	Solid rapidly disintegrating dosage form
EP0642784B1 (de) *	1993-09-07	1999-05-19	Gerhard Dr. Gergely	Brausemischung mit Alkalisalzen oder Lysinaten saurer, unlöslicher oder schwer löslicher Wirkstoffe
EP2307022A4 (de) *	2007-10-31	2011-08-24	Equitech Corp	Verbesserte nsaid-formulierungen
WO2013052019A1 (en) *	2011-08-19	2013-04-11	Mahmut Bilgic	Production method for effervescent formulations comprising diclofenac

2013
- 2013-01-18 EP EP13720143.0A patent/EP2804594A1/de not_active Withdrawn
- 2013-01-18 WO PCT/TR2013/000034 patent/WO2013109222A1/en active Application Filing

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Title
See references of WO2013109222A1 *

Also Published As

Publication number	Publication date
WO2013109222A1 (en)	2013-07-25

Publication	Publication Date	Title
WO1998029137A1 (fr)	1998-07-09	Compositions medicinales immediatement desintegrables
US11013736B2 (en)	2021-05-25	Oral solid preparation and use thereof
EP2563340A2 (de)	2013-03-06	Wasserlösliche pharmazeutische zusammensetzung
WO2013052019A1 (en)	2013-04-11	Production method for effervescent formulations comprising diclofenac
US9717692B2 (en)	2017-08-01	Effervescent formulations comprising dexketoprofen
WO2011078821A1 (en)	2011-06-30	Effervescent tablet and granule formulation comprising cefixime
WO2011129792A1 (en)	2011-10-20	Water dispersible formulations comprising cefpodoxime proxetil
WO2013109222A1 (en)	2013-07-25	Formulations comprising diclofenac as the active agent
WO2012060786A2 (en)	2012-05-10	Cefpodoxime proxetil formulations comprising viscosity agent
EP2608776A2 (de)	2013-07-03	Cefpodoximproxetil-formulierungen
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WO2014104989A1 (en)	2014-07-03	Pharmaceutical compositions comprising aripiprazole
EP2515859A1 (de)	2012-10-31	Schnell dispergierende brauseformulierung
EP3173077B1 (de)	2020-05-06	Tablettenformulierungen aus nimesulid und thiocolchicosid
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WO2012158127A2 (en)	2012-11-22	Water-soluble formulations comprising dexketoprofen
EP2793855B1 (de)	2015-12-16	Flurbiprofen-formulierungen
EP2793856B1 (de)	2015-12-16	Im mund zerfallende formulierungen aus flurbiprofen
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