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WO2013169218A1 - Pharmaceutical compositions of s-etodolac - Google Patents

Pharmaceutical compositions of s-etodolac Download PDF

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Publication number
WO2013169218A1
WO2013169218A1 PCT/TR2013/000151 TR2013000151W WO2013169218A1 WO 2013169218 A1 WO2013169218 A1 WO 2013169218A1 TR 2013000151 W TR2013000151 W TR 2013000151W WO 2013169218 A1 WO2013169218 A1 WO 2013169218A1
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WO
WIPO (PCT)
Prior art keywords
formulation
etodolac
range
formulation according
diluent
Prior art date
Application number
PCT/TR2013/000151
Other languages
French (fr)
Inventor
Mahmut Bilgic
Original Assignee
Mahmut Bilgic
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.)
Filing date
Publication date
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Publication of WO2013169218A1 publication Critical patent/WO2013169218A1/en

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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
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/407—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
    • A61K31/167—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
    • 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
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/425—Thiazoles
    • A61K31/426—1,3-Thiazoles
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds

Definitions

  • the present invention is related to pharmaceutical formulations comprising S-etodolac used in the treatment of symptoms and diagnoses of osteoarthritis, rheumatoid arthritis and ankylosing spondylitis; in the treatment of acute gouty arthritis, acute musculoskeletal pains, post-operative pain and dysmenorrhea.
  • Said formulations are characterized in being in tablet form.
  • S-etodolac was first disclosed in the patent application numbered US3939178.
  • antibacterial and antifungal activities of the molecule defined with the name 1,8- Diethyl-1, 3, 4,9-tetrahydropyrano(3,4-b)indol-l -acetic acid CAS was disclosed in addition to its anti-inflammatory and analgesic activities.
  • Etodolac is in 400 mg and 600 mg prolonged release tablet and 200, 300, 400, 500 mg film tablet forms on the market.
  • formulations comprising S-etodolac and/or its all pharmaceutically acceptable forms in the range of 10-80% in proportion to total weight of unit dose and formulated in tablet form can start their analgesic activity fast and effectively as they enter the blood stream fast and they increase drug efficiency by impeding potential side effects.
  • the first element of the present invention is pharmaceutical formulations which can be formulated in tablet form and comprise S-etodolac and/or all pharmaceutically acceptable forms thereof in the range of 10-80% in proportion to total weight of unit dose.
  • the present invention relates to pharmaceutical formulations which can be formulated in tablet form and comprise the active agent S-etodolac preferably in the range of 20-75%, more preferably in the range of 30-70% in proportion to total weight of unit dose.
  • subject of the present invention is that said formulation comprises the active agent S-etodolac in the range of 50-500 mg, preferably in the range of 100-450 mg, more preferably in the range of 150-350 mg.
  • the tablet formulations prepared according to the present invention can be in any of effervescent tablet, film coated tablet, enteric-coated tablet, prolonged release tablet, modified release tablet, delayed release tablet solid dosage forms.
  • the formulations prepared according to the present invention can preferably be in film coated tablet or modified release tablet forms.
  • the formulations prepared according to the present invention can comprise at least one pharmaceutically acceptable excipient in addition to S-etodolac which is used as the active agent.
  • excipients that can be used in the formulations of the present invention can be selected from a group comprising diluent, disintegrant, binder, glidant, lubricant, optionally coating agent or combinations thereof.
  • analgesic drugs such as S-etodolac are taken in high doses. Therefore, selection of the excipients that shall be used during formulation of the tablets comprising S-etodolac and the rate of these excipients used in the tablet formulation are significant for obtaining tablets which disperse fast and size of which do not pose any problems for patients during use.
  • the inventors have observed that they enable to obtain tablets which can disperse fast and have the required weight in the case that the formulations of the present invention comprise at least one diluent in the range of 10-50%, preferably in the range of 15- 40%.
  • the present invention relates to the formulations comprising S-etodolac to comprise at least one diluent in the range of 10-50%, preferably in the range of 15-40%.
  • the diluent that shall be used in said formulation is selected from a group comprising starch and starch derivatives, cellulose and cellulose derivatives, microcrystalline cellulose, lactose, sorbitol, silicon dioxide, dicalcium phosphate or a combination thereof.
  • the disintegrant that shall be used in the formulation prepared according to the present invention can be selected from a group comprising sodium starch glycolate, carboxymethyl cellulose calcium, carboxymethylcellulose sodium, microcrystalline cellulose, silicon dioxide, croscarmellose sodium, crospovidone, hydroxypropyl cellulose, methyl cellulose, povidone, magnesium aluminum silicate, starch or combinations thereof.
  • the inventors have seen that they can produce tablets with optimum dispersion and weight which are durable to production process in the case that the ratio of diluen disintegrant is in the range of 10: 1 to 1 :5 by weight, preferably in the range of 8: 1 to 1 :2 by weight, more preferably in the range of 5:1 to 1 : 1 by weight.
  • one characteristic of the formulations prepared according to the present invention is that the ratio of diluent:disintegrant is in the range of 10:1 to 1 :5 by weight, preferably in the range of 8:1 to 1 :2 by weight, more preferably in the range of 5: 1 to 1 : 1 by weight.
  • the binder used in the formulations prepared according to the present invention can be selected from a group comprising ethyl cellulose, gelatin, hydroxyethyl cellulose, hydroxymethyl cellulose, hydroxypropyl cellulose, hypromellose, magnesium aluminum silicate, methyl cellulose, povidone, sorbitol salt or a combination thereof.
  • the glidant that shall be used in the formulations of the present invention can be selected from a group comprising magnesium silicate, silicon dioxide, colloidal silicon dioxide, starch, talc, tribasic calcium phosphate or a combination thereof.
  • the lubricant that shall be 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, potassium benzoate, sodium benzoate.
  • the film coating agent that shall be used in the formulations of the present invention can be selected from a group comprising titanium dioxide, polyvinyl alcohol, polyethylene glycol, talc, lecithin or a combination thereof.
  • the film coating agent marketed under the name Opadry Yellow® can be used.
  • formulations of the present invention comprises at least another active agent in addition to S-etodolac used as the active agent.
  • the second active agent that can be used in the formulations of the present invention can be selected from antiseptic, antipyretic, anti-inflammatory, muscle relaxant, analgesic, non-steroid anti-inflammatory, H2 receptor antagonist drugs or combinations thereof.
  • the formulations of the present invention can preferably comprise an analgesic and/or antipyretic drug, more preferably paracetamol or thiocolchicoside as the second active agent in addition to S-etodolac.
  • the formulations of the present invention can preferably comprise an H2 receptor antagonist, more preferably famotidine as the second active agent in addition to S-etodolac.
  • the formulations prepared according to the present invention can comprise S-etodolac in the range of 10-80%, diluent in the range of 10-50%, disintegrant in the range of 1 -25%, binder in the range of 0.5-5%, glidant in the range of 0.1-1%, lubricant in the range of 1 -5% and optionally the coating agent in the range of 0.5-5% in proportion to total weight of the unit dose amount.
  • S- etodolac, the diluent and the disintegrant are mixed, the mixture is granulated with a granulation solution comprising the binder.
  • the obtained granules are dried and mixed with the diluent, disintegrant and glidant.
  • the final mixture is lubricated with the lubricant.
  • tablet compression is started. The tablets compressed are coated with the coating solution comprising coating agent.
  • the formulations of the present invention can be used in the treatment of symptoms and diagnoses of osteoarthritis, rheumatoid arthritis and ankylosing spondylitis; in the treatment of acute gouty arthritis, acute musculoskeletal pains, postoperative pain and dysmenorrhea.
  • the example below is given in order to explain the invention in more detail yet it does not limit the present invention.
  • the formulation given above is prepared by wet granulation method. S-Etodolac, the diluent and the disintegrant are mixed and the mixture is granulated with a granulation solution comprising the binder. The obtained granules are dried and mixed with the diluent, disintegrant and glidant. This mixture is lubricated with the lubricant. After the lubrication, tablet compression is started. The compressed tablets are coated with a coating solution comprising the coating agent.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Medicinal Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pain & Pain Management (AREA)
  • Molecular Biology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The present invention is related to pharmaceutical formulations comprising S-etodolac used in the treatment of symptoms and diagnoses of osteoarthritis, rheumatoid arthritis and ankylosing spondylitis; in the treatment of acute gouty arthritis, acute musculoskeletal pains, postoperative pain and dysmenorrhea. Said formulations are characterized in being in tablet form.

Description

PHARMACEUTICAL COMPOSITIONS OF S-ETODOLAC
The present invention is related to pharmaceutical formulations comprising S-etodolac used in the treatment of symptoms and diagnoses of osteoarthritis, rheumatoid arthritis and ankylosing spondylitis; in the treatment of acute gouty arthritis, acute musculoskeletal pains, post-operative pain and dysmenorrhea. Said formulations are characterized in being in tablet form.
S-etodolac was first disclosed in the patent application numbered US3939178. In said document, antibacterial and antifungal activities of the molecule defined with the name 1,8- Diethyl-1, 3, 4,9-tetrahydropyrano(3,4-b)indol-l -acetic acid CAS was disclosed in addition to its anti-inflammatory and analgesic activities.
Figure imgf000002_0001
Etodolac is in 400 mg and 600 mg prolonged release tablet and 200, 300, 400, 500 mg film tablet forms on the market.
For drugs having analgesic effect such as etodolac, their time to reach the minimum plasma concentration in blood when taken in body is quite effective on their time to show their analgesic effect. The slower the medications comprising etodolac reach to minimum plasma concentration when taken in the body, the slower they start their analgesic activity. Thus, the pain that the patient suffers takes longer to wear off The rate of reaching the minimum plasma concentration of etodolac depends on its half life. The longer the half lives of etodolac and its pharmaceutically acceptable derivatives are, the slower they enter the bloodstream and start their analgesic activity. This results in reaching the plasma concentration required to reach fast and sufficient level of drug efficiency by using higher doses of etodolac. Therefore, intake of high doses of the active agent etodolac causes several side effects such as increase in gastrointestinal adverse effects. Depending on that, various stomach disorders are seen in the patient and an ineffective treatment is obtained during use of medications comprising etodolac.
The patent application numbered W09527713 is related to preparation of meglumine salts of S-etodolac. In said document, it is claimed that the problems of S-etodolac such as reaching the minimum plasma level slowly and late analgesic activity as mentioned in the prior art can be solved by arguing that the disclosed form has the desired biological activity. However, it has been seen that the problems mentioned in the prior art maintain in the formulations comprising the free form of the molecule S-etodolac and/or its other pharmaceutically acceptable forms and the patients cannot be treated effectively as the analgesic activity of these medications is delayed.
According to this, there is need to develop new formulations which can enter the bloodstream fast and, thus, have analgesic activity; provide to reach sufficient drug efficiency by minimizing potential side effects; and comprise the free form of the molecule S-etodolac and/or its other pharmaceutically acceptable forms .
The inventors have surprisingly seen that formulations comprising S-etodolac and/or its all pharmaceutically acceptable forms in the range of 10-80% in proportion to total weight of unit dose and formulated in tablet form can start their analgesic activity fast and effectively as they enter the blood stream fast and they increase drug efficiency by impeding potential side effects.
Description of the Invention
The first element of the present invention is pharmaceutical formulations which can be formulated in tablet form and comprise S-etodolac and/or all pharmaceutically acceptable forms thereof in the range of 10-80% in proportion to total weight of unit dose. In another aspect, the present invention relates to pharmaceutical formulations which can be formulated in tablet form and comprise the active agent S-etodolac preferably in the range of 20-75%, more preferably in the range of 30-70% in proportion to total weight of unit dose.
In another aspect, subject of the present invention is that said formulation comprises the active agent S-etodolac in the range of 50-500 mg, preferably in the range of 100-450 mg, more preferably in the range of 150-350 mg.
The tablet formulations prepared according to the present invention can be in any of effervescent tablet, film coated tablet, enteric-coated tablet, prolonged release tablet, modified release tablet, delayed release tablet solid dosage forms.
The formulations prepared according to the present invention can preferably be in film coated tablet or modified release tablet forms. The formulations prepared according to the present invention can comprise at least one pharmaceutically acceptable excipient in addition to S-etodolac which is used as the active agent.
The excipients that can be used in the formulations of the present invention can be selected from a group comprising diluent, disintegrant, binder, glidant, lubricant, optionally coating agent or combinations thereof.
Analgesic drugs such as S-etodolac are taken in high doses. Therefore, selection of the excipients that shall be used during formulation of the tablets comprising S-etodolac and the rate of these excipients used in the tablet formulation are significant for obtaining tablets which disperse fast and size of which do not pose any problems for patients during use. In the studies they conducted, the inventors have observed that they enable to obtain tablets which can disperse fast and have the required weight in the case that the formulations of the present invention comprise at least one diluent in the range of 10-50%, preferably in the range of 15- 40%. According to this in another aspect, the present invention relates to the formulations comprising S-etodolac to comprise at least one diluent in the range of 10-50%, preferably in the range of 15-40%.
Another characteristic of the present invention is that the diluent that shall be used in said formulation is selected from a group comprising starch and starch derivatives, cellulose and cellulose derivatives, microcrystalline cellulose, lactose, sorbitol, silicon dioxide, dicalcium phosphate or a combination thereof.
In another aspect, the disintegrant that shall be used in the formulation prepared according to the present invention can be selected from a group comprising sodium starch glycolate, carboxymethyl cellulose calcium, carboxymethylcellulose sodium, microcrystalline cellulose, silicon dioxide, croscarmellose sodium, crospovidone, hydroxypropyl cellulose, methyl cellulose, povidone, magnesium aluminum silicate, starch or combinations thereof.
In addition to the indispensability of fast dispersion and optimum weight, sufficient hardness to endure the production process is another characteristic feature required for tablets comprising S-etodolac. As a result of the studies they conducted, the inventors have observed that the ratio of the diluent to the disintegrant used in the formulation by weight is a significant parameter to obtain tablets which have the required hardness and thus optimum dispersion time. The inventors have seen that they can produce tablets with optimum dispersion and weight which are durable to production process in the case that the ratio of diluen disintegrant is in the range of 10: 1 to 1 :5 by weight, preferably in the range of 8: 1 to 1 :2 by weight, more preferably in the range of 5:1 to 1 : 1 by weight. According to this, one characteristic of the formulations prepared according to the present invention is that the ratio of diluent:disintegrant is in the range of 10:1 to 1 :5 by weight, preferably in the range of 8:1 to 1 :2 by weight, more preferably in the range of 5: 1 to 1 : 1 by weight.
In another aspect, the binder used in the formulations prepared according to the present invention can be selected from a group comprising ethyl cellulose, gelatin, hydroxyethyl cellulose, hydroxymethyl cellulose, hydroxypropyl cellulose, hypromellose, magnesium aluminum silicate, methyl cellulose, povidone, sorbitol salt or a combination thereof.
The glidant that shall be used in the formulations of the present invention can be selected from a group comprising magnesium silicate, silicon dioxide, colloidal silicon dioxide, starch, talc, tribasic calcium phosphate or a combination thereof.
The lubricant that shall be 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, potassium benzoate, sodium benzoate.
The film coating agent that shall be used in the formulations of the present invention can be selected from a group comprising titanium dioxide, polyvinyl alcohol, polyethylene glycol, talc, lecithin or a combination thereof. For example, the film coating agent marketed under the name Opadry Yellow® can be used.
Another characteristic of the formulations of the present invention is that said formulation comprises at least another active agent in addition to S-etodolac used as the active agent. According to this, the second active agent that can be used in the formulations of the present invention can be selected from antiseptic, antipyretic, anti-inflammatory, muscle relaxant, analgesic, non-steroid anti-inflammatory, H2 receptor antagonist drugs or combinations thereof. Optionally, the formulations of the present invention can preferably comprise an analgesic and/or antipyretic drug, more preferably paracetamol or thiocolchicoside as the second active agent in addition to S-etodolac.
Optionally, the formulations of the present invention can preferably comprise an H2 receptor antagonist, more preferably famotidine as the second active agent in addition to S-etodolac.
The formulations prepared according to the present invention can comprise S-etodolac in the range of 10-80%, diluent in the range of 10-50%, disintegrant in the range of 1 -25%, binder in the range of 0.5-5%, glidant in the range of 0.1-1%, lubricant in the range of 1 -5% and optionally the coating agent in the range of 0.5-5% in proportion to total weight of the unit dose amount.
According to the method used for preparation of the formulations of the present invention, S- etodolac, the diluent and the disintegrant are mixed, the mixture is granulated with a granulation solution comprising the binder. The obtained granules are dried and mixed with the diluent, disintegrant and glidant. The final mixture is lubricated with the lubricant. Following the lubrication, tablet compression is started. The tablets compressed are coated with the coating solution comprising coating agent.
The formulations of the present invention can be used in the treatment of symptoms and diagnoses of osteoarthritis, rheumatoid arthritis and ankylosing spondylitis; in the treatment of acute gouty arthritis, acute musculoskeletal pains, postoperative pain and dysmenorrhea. The example below is given in order to explain the invention in more detail yet it does not limit the present invention.
EXAMPLE: Film coated tablet formulations comprising S-etodolac
Figure imgf000007_0001
The formulation given above is prepared by wet granulation method. S-Etodolac, the diluent and the disintegrant are mixed and the mixture is granulated with a granulation solution comprising the binder. The obtained granules are dried and mixed with the diluent, disintegrant and glidant. This mixture is lubricated with the lubricant. After the lubrication, tablet compression is started. The compressed tablets are coated with a coating solution comprising the coating agent.

Claims

1. A pharmaceutical formulation that can be formulated in tablet form, characterized in that said formulation comprises S-etodolac and/or pharmaceutically acceptable forms thereof in the range of 10-80% in proportion to total weight of the unit dose amount.
2. The formulation according to claim 1, characterized in that said formulation comprises S-etodolac and/or pharmaceutically acceptable forms thereof in the range of 20-75% in proportion to total weight of the unit dose amount.
3. The formulation according to claim 2, characterized in that said formulation comprises S-etodolac and/or pharmaceutically acceptable forms thereof in the range of 30-70% in proportion to total weight of the unit dose amount.
4. The formulation according to claims 1-3, characterized in that said formulation comprises S-etodolac and/or pharmaceutically acceptable forms thereof in doses of 50-500 mg.
5. The formulation according to claim 4, characterized in that said formulation comprises the active agent S-etodolac in doses of 100-450 mg.
6. The formulation according to claim 5, characterized in that said formulation comprises the active agent S-etodolac in doses of 150-350 mg.
7. The formulation according to claims 1-6, characterized in that the tablet formulations can be in any of the solid dosage forms of effervescent tablet, film coated tablet, enteric-coated tablet, prolonged release tablet, modified release tablet, delayed release tablet.
8. The formulation according to claim 7, characterized in that the tablet formulations are in forms of film coated tablet or modified release tablet.
9. The formulation according to any preceding claims, characterized in that the excipients that can be used in said formulation are selected from a group comprising diluent, disintegrant, binder, glidant, lubricant, optionally coating agent or combinations thereof.
10. The formulation according to claim 9, characterized in that said formulation comprises at least one diluent in the range of 10-50%.
1 1. The formulation according to claim 10, characterized in that said formulation comprises at least one diluent in the range of 15-40%.
12. The formulation according to claims 9-1 1, characterized in that the diluent that can be used in said formulation is selected from a group comprising starch and starch derivatives, cellulose and cellulose derivatives, microcrystalline cellulose, lactose, sorbitol, silicon dioxide, dicalcium phosphate or a combination thereof.
13. The formulation according to claim 9, characterized in that the disintegrant that can be used in said formulation is selected from a group comprising sodium starch glycolate, carboxymethyl cellulose calcium, carboxymethylcellulose sodium, microcrystalline cellulose, silicon dioxide, croscarmellose sodium, crospovidone, hydroxypropyl cellulose, methyl cellulose, povidone, magnesium aluminum silicate, starch or combinations thereof.
14. The formulation according to claims 9-13, characterized in that the ratio of the diluent to the disintegrant is in the range of 10: 1 to 1 :5 by weight.
15. The formulation according to claim 14, characterized in that the ratio of the diluent to the disintegrant is in the range of 8:1 to 1 :2 by weight.
16. The formulation according to claim 15 characterized in that the ratio of the diluent to the disintegrant is in the range of 5:1 to 1 : 1 by weight.
17. The formulation according to any preceding claims, characterized in that said formulation optionally comprises at least one more active agent in addition to S- etodolac used as the active agent.
18. The formulation according to claim 17 characterized in that the second active agent that can be used in said formulation is selected from antiseptic, antipyretic, antiinflammatory, muscle relaxant, analgesic, non-steroid anti-inflammatory, H2 receptor antagonist drugs or combinations thereof.
19. The formulation according to claim 18 characterized in that said formulation optionally comprises an analgesic and/or antipyretic drug as the second active agent in addition to S-etodolac.
20. The formulation according to claim 19 characterized in said formulation optionally comprises paracetamol or thiocolchicoside as the second active agent in addition to S- etodolac.
21. The formulation according to claims 17-20 characterized in that said formulation optionally comprises an H2 receptor antagonist as the second active agent in addition to S-etodolac.
22. The formulation according to claim 21 characterized in said formulation preferably comprises famotidine as the second active agent in addition to S-etodolac.
23. The formulation according to any preceding claims, characterized in that said formulation comprises S-etodolac in the range of 10-80%, diluent in the range of 10- 50%, disintegrant in the range of 1-25%, binder in the range of 0.5-5%, glidant in the range of 0.1 -1%, lubricant in the range of 1 -5% and optionally the coating agent in the range of 0.5-5% in proportion to total weight of the unit dose amount.
24. The formulation according to any preceding claims, characterized in that the method used to prepare the formulation comprises the steps of
• Mixing S-etodolac, the diluent and the disintegrant,
• Granulating the mixture by using the granulation solution comprising the binder,
• Drying the obtained granules and mixing them with the diluent, disintegrant and the glidant,
• Lubricating the mixture with the lubricant and compressing it in tablet form,
• Coating the compressed tablets with the coating solution comprising the coating agent.
PCT/TR2013/000151 2012-05-08 2013-05-08 Pharmaceutical compositions of s-etodolac WO2013169218A1 (en)

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TR201205322 2012-05-08

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2018004498A1 (en) * 2016-06-30 2018-01-04 Imuneks Farma Ilac San. Ve Tic. A.S. Nsaid and h2 receptor antagonist combinations for the treatment of pain and inflammation
WO2019203759A3 (en) * 2018-01-03 2020-01-23 Pisak Mehmet Nevzat Combinations of etodolac with h2 receptor antagonists for the treatment of pain and inflammation.
CN114699380A (en) * 2021-12-27 2022-07-05 南京联智医药科技有限公司 Etodolac tablet and preparation method thereof

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3939178A (en) 1971-06-01 1976-02-17 American Home Products Corporation Certain pyrano [3,4-b]indoles and thiopyrano[3,4-b]indoles
WO1995027713A1 (en) 1994-04-12 1995-10-19 Chiroscience Limited Process for the resolution of etodolac using glucamine derivatives
EP0748628A2 (en) * 1995-06-13 1996-12-18 American Home Products Corporation Oral formulations of S(+)-Etodolac

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3939178A (en) 1971-06-01 1976-02-17 American Home Products Corporation Certain pyrano [3,4-b]indoles and thiopyrano[3,4-b]indoles
WO1995027713A1 (en) 1994-04-12 1995-10-19 Chiroscience Limited Process for the resolution of etodolac using glucamine derivatives
EP0748628A2 (en) * 1995-06-13 1996-12-18 American Home Products Corporation Oral formulations of S(+)-Etodolac

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2018004498A1 (en) * 2016-06-30 2018-01-04 Imuneks Farma Ilac San. Ve Tic. A.S. Nsaid and h2 receptor antagonist combinations for the treatment of pain and inflammation
WO2019203759A3 (en) * 2018-01-03 2020-01-23 Pisak Mehmet Nevzat Combinations of etodolac with h2 receptor antagonists for the treatment of pain and inflammation.
CN114699380A (en) * 2021-12-27 2022-07-05 南京联智医药科技有限公司 Etodolac tablet and preparation method thereof

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