WO2014035356A1 - Tablet formulations comprising a quinone derivative active agent - Google Patents
Tablet formulations comprising a quinone derivative active agent Download PDFInfo
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- WO2014035356A1 WO2014035356A1 PCT/TR2013/000283 TR2013000283W WO2014035356A1 WO 2014035356 A1 WO2014035356 A1 WO 2014035356A1 TR 2013000283 W TR2013000283 W TR 2013000283W WO 2014035356 A1 WO2014035356 A1 WO 2014035356A1
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- formulations
- film coated
- coated tablet
- lactose
- pharmaceutically acceptable
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- 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
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
- A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
-
- 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
- A61K31/12—Ketones
- A61K31/122—Ketones having the oxygen directly attached to a ring, e.g. quinones, vitamin K1, anthralin
Definitions
- the present invention is related to pharmaceutical formulations in tablet form comprising a quinone derivative active agent, production method of said formulations and their areas of use.
- Idebenone is a quinone derivative drug which has the chemical formula of 2-(10- hydroxydecyl)-5,6-dimethoxy-3-methyl- cyclohexa-2,5-diene-l ,4-dione and developed by the firm Takeda in order to be used in the treatment of Alzheimer's disease and other mental disorders.
- the active agent is marketed in 45 mg oral tablet form (Mnesis®) in the treatment of central nervous system disorders in Europe and in 150 mg oral tablet form ( Catena®) in the treatment of Friedreich's ataxia in Canada.
- Idebenone is a lipophilic molecule which has very low solubility in aqueous media.
- the active agent in the drugs in tablet form obtained in the case that the formulations comprising the active agent are compressed in tablet form cannot dissolve in bodily fluid entirely.
- Water solubility of an active agent is one of the most critical factors influencing the bioavailability of the pharmaceutical formulation comprising the active agent.
- Lipophilic active agents such as idebenone have poor bioavailability as they cannot dissolve in water.
- Low absorption and bioavailability of a drug prevents enabling efficient treatment.
- the present invention is related to pharmaceutical formulations in tablet form comprising idebenone, production method of these formulations and their areas of use.
- the pharmaceutical formulations of the present invention are characterized in being in tablet form.
- tablet formulations of the present invention are in film coated tablet form.
- the tablet formulations of the present invention are more advantageous in comparison to parenteral dosage forms as they are patient friendly, have long shelf life and can be produced easily.
- the film coated tablet formulations of the present invention comprise idebenone as the active agent in the range of 1% and 50%, preferably in the range of 1% and 45%, more preferably in the range of 1% and 40% by weight.
- Idebenone comprised in the film coated tablet formulations of the present invention can be in the form of idebenone or its pharmaceutically acceptable salt, racemate, solvate, hydrate, anhydrate, different polymorphic form and amorphous form or combinations thereof.
- the film coated tablet formulations of the present invention comprise at least one pharmaceutically acceptable excipient in addition to the active agent selected form a group comprising disintegrant, diluent, liibricant, glidant, binder, effervescent couple composed of at least one effervescent acid and at least one effervescent base, coloring agent, pH regulating agent, surfactant, stabilizing agent, sweetener and/or taste regulating agent, flavoring agent.
- the active agent selected form a group comprising disintegrant, diluent, liibricant, glidant, binder, effervescent couple composed of at least one effervescent acid and at least one effervescent base, coloring agent, pH regulating agent, surfactant, stabilizing agent, sweetener and/or taste regulating agent, flavoring agent.
- a significant factor affecting the dissolution rate of pharmaceutical formulations is type and amount of the excipients in the formulations in addition the active agent.
- the film coated tablet formulations of the present invention comprise at least one filling agent selected from a group comprising calcium carbonate, dibasic calcium phosphate, tribasic calcium phosphate, calcium sulfate, microcrystalline cellulose, dextrose, fructose, lactitol, lactose or pharmaceutically acceptable derivatives thereof, magnesium carbonate, magnesium oxide, maltitol, maltodextrin, maltose, mannitol, simethicone, sorbitol, starch, sodium chloride, sucrose, talc, xylitol.
- a filling agent selected from a group comprising calcium carbonate, dibasic calcium phosphate, tribasic calcium phosphate, calcium sulfate, microcrystalline cellulose, dextrose, fructose, lactitol, lactose or pharmaceutically acceptable derivatives thereof, magnesium carbonate, magnesium oxide, maltitol, maltodextrin, maltose, mannitol, si
- the inventors have discovered that the highest dissolution and therefore the highest bioavailability in the formulations can be obtained in the case that the formulations are prepared in tablet form and said tablet formulation comprises lactose or a pharmaceutically acceptable derivative thereof as the filling agent at least at 50% by weight.
- a characteristic feature of the film coated tablet formulations of the present invention is that said formulations comprise lactose or a pharmaceutically acceptable derivative thereof in the range of 50% and 85% by weight.
- a characteristic feature of the film coated tablet formulations of the present invention is that said formulations comprise lactose or a pharmaceutically acceptable derivative thereof in the range of 50% and 80% by weight.
- the ratio of lactose or a pharmaceutically acceptable derivative thereof and idebenone comprised in the formulations of the present invention to each other is in the range of 1.5 and 10, preferably in the range of 2 and 10, more preferably in the range of 2.5 and 10 by weight.
- lactose or a pharmaceutically acceptable derivative thereof used herein refers to lactose, lactose monohydrate or lactose anhydrate.
- the lactose derivative preferred in the film coated tablet formulations of the present invention is lactose monohydrate.
- alkali metal carbonates such as calcium carbonate
- alkali metal phosphates such as calcium phosphate
- alkali metal sulfates such as calcium sulfate
- cellulose derivatives such as cellulose, microcrystalline cellulose, cellulose acetate
- magnesium oxide dextrin, fructose, dextrose, glyceryl palmiostearate
- lactitol kaolin
- lactose, maltose, mannitol, simethicone, sorbitol, starch, pregelatinized starch, talc, xylitol and/or anhydrates, hydrates and/or pharmaceutically acceptable derivatives thereof or combinations thereof can be used in the film coated tablet formulations of the present invention.
- starches such as potato starch, corn starch, wheat starch; sugars such as sucrose, glucose, dextrose, lactose, ⁇ maltodextrin; natural and synthetic gums; gelatine; cellulose derivatives such as microcrystalline cellulose, hydroxypropyl cellulose, hydroxyethyl cellulose, hydroxypropyl methyl cellulose, carboxymethyl cellulose, methyl cellulose, ethyl cellulose; polyvinylpyrrolidone (povidone); polyethylene glycol (PEG); waxes; calcium carbonate; calcium phosphate; alcohols such as sorbitol, xylitol, mannitol and water or a combination thereof can be used in the film coated tablet formulations of the present invention.
- sugars such as sucrose, glucose, dextrose, lactose, ⁇ maltodextrin
- natural and synthetic gums gelatine
- cellulose derivatives such as microcrystalline cellulose, hydroxypropyl cellulose, hydroxye
- cellulose derivatives such as cross-linked carboxymethyl cellulose and/or its salts, microcrystalline cellulose, cellulose, hydroxy propyl cellulose, hydroxy ethyl cellulose, hydroxy propyl methyl cellulose, hydroxy propyl ethyl cellulose, methyl cellulose; sodium starch glycolate, alginic acid, sodium alginate, chitosan, colloidal silicon dioxide, starch, pregelatinized starch, polyvinylpyrrolidone, cross-linked polyvinylpyrrolidone or combinations thereof can be used in the film coated tablet formulations of the present invention.
- metallic stearates such as magnesium stearate, calcium stearate, aluminum stearate
- fatty acid esters such as sodium stearyl fumarate
- fatty acids such as stearic acid
- fatty alcohols glyceryl behenate, mineral oil, paraffins, hydrogenated vegetable oil, leucine, polyethylene glycols
- metallic lauryl sulfate such as sodium lauryl sulfate, magnesium lauryl sulfate
- sodium chloride sodium benzoate, sodium acetate and talc or a combination thereof
- the film coating agents that that can be used for flm coating of the film coated tablet formulations of the present invention can be selected from a group comprising cellulose derivatives such as hydroxypropyl cellulose, hydroxypropyl methyl cellulose, hydroxymethyl cellulose, ethyl cellulose, methyl hydroxyethyl cellulose and sodium carboxymethyl cellulose; synthetic polymers such as polyvinyl acetal diethyl amino acetate, aminoalkyl methacrylate copolymers and polyvinylpyrrolidone; polysaccharides such as pullulan; titanium dioxide, triacetin; black, yellow and/or red iron oxides or combinations thereof.
- cellulose derivatives such as hydroxypropyl cellulose, hydroxypropyl methyl cellulose, hydroxymethyl cellulose, ethyl cellulose, methyl hydroxyethyl cellulose and sodium carboxymethyl cellulose
- synthetic polymers such as polyvinyl acetal diethyl amino acetate, aminoalkyl meth
- compositions of the present invention can optionally comprise at least another active agent.
- the other active agent that can be used in the formulations can be selected from antacid, anticholinergic, antispasmodic, antiemetic, antibiotic, antipropulsive, antiallergic, antidiarrheal, antiobesity, antithrombotic, antifibrinolytic, antianemic, antihypertensive, antifungal, antipruritic, antipsoriatic, antibiotic, antiseptic, antiacne, antibacterial, antimycotic, anti-dementia, antiviral, antineoplastic, antiarrhythmic, antiadrenergic, antiepileptic,- anti- parkinson, antiprotozoal, anthelmintic, anti-inflammatory, diuretic, laxative, sulphonamide, imidazole, corticosteroid, thiazolidinedione, biguanide, immunostimulant, immunosuppressant, myorelaxant, analgesic, psycholeptic, psychoanaleptic peripheral vaso
- the other active agent or active agent group preferred for the formulations of the present invention is at least one anti-dementia agent and said anti-dementia agents are selected from a group comprising donepezil, galantamine, memantine, rivastigmine, ginkgo biloba extract, tacrine and or their pharmaceutically acceptable salts, enantiomers, hydrates, anhydrates etc. derivatives or binary or ternary combinations thereof.
- the present invention presents a method for production of idebenone tablet formulations.
- a characteristic feature of the formulations of the present invention is that said formulations are produced by wet granulation method.
- Said production method comprises the steps of mixing the active agent or if available at least one other active agent with lactose monohydrate and at least another excipient; wet- granulating the mixture; drying and sieving the granules; adding at least another pharmaceutically acceptable excipient into the dried granules; compressing the final mixture in tablet form and film-coating the obtained tablet.
- the film coated idebenone tablet formulations of the present invention are used in the treatment of cerebral arteriosclerosis, symptoms following stroke and cerebral hemorrhage, age-associated cognitive decline, chronic cerebrovascular disease, multi-infarct dementia and mild and moderate Alzheimer's type dementia and frailty, speech disorders, memory loss, short attention span associated with these diseases, symptoms of vascular and degenerative cerebral pathologies such as psychomotor activity and depression.
- Idebenone, diluent and lactose monohydrate are mixed.
- the mixture is wet-granulated with a granulation solution comprising the binder and at least one solvent.
- the granules are dried and sieved.
- the disintegrant is added to the obtained dry granules and they are mixed.
- the mixture is treated with the lubricant.
- the final mixture is compressed in tablet form and the tablets are coated with film.
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Abstract
The present invention is related to pharmaceutical formulations in tablet form comprising a quinone derivative active agent, production method of said formulations and their areas of use.
Description
DESCRIPTION
TABLET FORMULATIONS COMPRISING A QUINONE DERIVATIVE ACTIVE AGENT
The present invention is related to pharmaceutical formulations in tablet form comprising a quinone derivative active agent, production method of said formulations and their areas of use.
The Prior Art
Idebenone is a quinone derivative drug which has the chemical formula of 2-(10- hydroxydecyl)-5,6-dimethoxy-3-methyl- cyclohexa-2,5-diene-l ,4-dione and developed by the firm Takeda in order to be used in the treatment of Alzheimer's disease and other mental disorders.
The active agent is marketed in 45 mg oral tablet form (Mnesis®) in the treatment of central nervous system disorders in Europe and in 150 mg oral tablet form ( Catena®) in the treatment of Friedreich's ataxia in Canada.
In addition to the indications given, effective use of the active agent in other indications (such as neuromuscular diseases, MELAS syndrome, primary MS, Leber 's Hereditary Optic Neuropathy and DMD-Duchenne muscular dystrophy) is also being investigated.
Idebenone is a lipophilic molecule which has very low solubility in aqueous media. In line with this, it is seen that the active agent in the drugs in tablet form obtained in the case that the formulations comprising the active agent are compressed in tablet form cannot dissolve in bodily fluid entirely.
Water solubility of an active agent is one of the most critical factors influencing the bioavailability of the pharmaceutical formulation comprising the active agent. Lipophilic active agents such as idebenone have poor bioavailability as they cannot dissolve in water. Low absorption and bioavailability of a drug prevents enabling efficient treatment.
In the prior art, a method which is frequently used for active agents having low bioavailability could be formulating the active agent in parenteral form. The patent applications US2010130619 and US2010129431 disclose parenteral idebenone formulations. However, it requires pretty hard and laborious production steps to formulate an active agent having low
water-solubility for parenteral use. On the other hand, parental formulations are not generally preferred by patients due to their manner of application. Therefore, it is not preferable to produce this type of active agents in parenteral form.
In the prior art, there are other solutions in order to improve bioavailability of lipophilic drugs. The most known ones of these methods can be listed as changing the crystalline structure of the active agent by one of micronization, spraying or freezing methods or solubilize the active agent by using solubility enhancing agents, surfactants, complexing agents etc. in the formulations.
However, these methods are considerably laborious and costly as well as not certain to provide bioavailability in the obtained product.
For this reason, there is need to develop new formulations comprising idebenone which can provide high bioavailability, can be produced easily and are patient-friendly.
Detailed Description of the Invention
The present invention is related to pharmaceutical formulations in tablet form comprising idebenone, production method of these formulations and their areas of use.
The pharmaceutical formulations of the present invention are characterized in being in tablet form.
Another characteristic feature of the tablet formulations of the present invention is that the formulations are in film coated tablet form. The tablet formulations of the present invention are more advantageous in comparison to parenteral dosage forms as they are patient friendly, have long shelf life and can be produced easily.
The film coated tablet formulations of the present invention comprise idebenone as the active agent in the range of 1% and 50%, preferably in the range of 1% and 45%, more preferably in the range of 1% and 40% by weight.
Idebenone comprised in the film coated tablet formulations of the present invention can be in the form of idebenone or its pharmaceutically acceptable salt, racemate, solvate, hydrate, anhydrate, different polymorphic form and amorphous form or combinations thereof.
The film coated tablet formulations of the present invention comprise at least one pharmaceutically acceptable excipient in addition to the active agent selected form a group
comprising disintegrant, diluent, liibricant, glidant, binder, effervescent couple composed of at least one effervescent acid and at least one effervescent base, coloring agent, pH regulating agent, surfactant, stabilizing agent, sweetener and/or taste regulating agent, flavoring agent.
A significant factor affecting the dissolution rate of pharmaceutical formulations is type and amount of the excipients in the formulations in addition the active agent.
The film coated tablet formulations of the present invention comprise at least one filling agent selected from a group comprising calcium carbonate, dibasic calcium phosphate, tribasic calcium phosphate, calcium sulfate, microcrystalline cellulose, dextrose, fructose, lactitol, lactose or pharmaceutically acceptable derivatives thereof, magnesium carbonate, magnesium oxide, maltitol, maltodextrin, maltose, mannitol, simethicone, sorbitol, starch, sodium chloride, sucrose, talc, xylitol.
During their studies for new formulations comprising idebenone, the inventors have discovered that the highest dissolution and therefore the highest bioavailability in the formulations can be obtained in the case that the formulations are prepared in tablet form and said tablet formulation comprises lactose or a pharmaceutically acceptable derivative thereof as the filling agent at least at 50% by weight.
A characteristic feature of the film coated tablet formulations of the present invention is that said formulations comprise lactose or a pharmaceutically acceptable derivative thereof in the range of 50% and 85% by weight.
A characteristic feature of the film coated tablet formulations of the present invention is that said formulations comprise lactose or a pharmaceutically acceptable derivative thereof in the range of 50% and 80% by weight.
The ratio of lactose or a pharmaceutically acceptable derivative thereof and idebenone comprised in the formulations of the present invention to each other is in the range of 1.5 and 10, preferably in the range of 2 and 10, more preferably in the range of 2.5 and 10 by weight.
"Lactose or a pharmaceutically acceptable derivative thereof used herein refers to lactose, lactose monohydrate or lactose anhydrate.
The lactose derivative preferred in the film coated tablet formulations of the present invention is lactose monohydrate.
As the diluent; alkali metal carbonates such as calcium carbonate; alkali metal phosphates such as calcium phosphate; alkali metal sulfates such as calcium sulfate; cellulose derivatives such as cellulose, microcrystalline cellulose, cellulose acetate; magnesium oxide, dextrin, fructose, dextrose, glyceryl palmiostearate, lactitol, kaolin, lactose, maltose, mannitol, simethicone, sorbitol, starch, pregelatinized starch, talc, xylitol and/or anhydrates, hydrates and/or pharmaceutically acceptable derivatives thereof or combinations thereof can be used in the film coated tablet formulations of the present invention.
As the binder; starches such as potato starch, corn starch, wheat starch; sugars such as sucrose, glucose, dextrose, lactose,■ maltodextrin; natural and synthetic gums; gelatine; cellulose derivatives such as microcrystalline cellulose, hydroxypropyl cellulose, hydroxyethyl cellulose, hydroxypropyl methyl cellulose, carboxymethyl cellulose, methyl cellulose, ethyl cellulose; polyvinylpyrrolidone (povidone); polyethylene glycol (PEG); waxes; calcium carbonate; calcium phosphate; alcohols such as sorbitol, xylitol, mannitol and water or a combination thereof can be used in the film coated tablet formulations of the present invention.
As the disintegrant; cellulose derivatives such as cross-linked carboxymethyl cellulose and/or its salts, microcrystalline cellulose, cellulose, hydroxy propyl cellulose, hydroxy ethyl cellulose, hydroxy propyl methyl cellulose, hydroxy propyl ethyl cellulose, methyl cellulose; sodium starch glycolate, alginic acid, sodium alginate, chitosan, colloidal silicon dioxide, starch, pregelatinized starch, polyvinylpyrrolidone, cross-linked polyvinylpyrrolidone or combinations thereof can be used in the film coated tablet formulations of the present invention.
As the lubricant; metallic stearates (such as magnesium stearate, calcium stearate, aluminum stearate), fatty acid esters (such as sodium stearyl fumarate), fatty acids (such as stearic acid), fatty alcohols, glyceryl behenate, mineral oil, paraffins, hydrogenated vegetable oil, leucine, polyethylene glycols, metallic lauryl sulfate (such as sodium lauryl sulfate, magnesium lauryl sulfate), sodium chloride, sodium benzoate, sodium acetate and talc or a combination thereof can be used in the film coated tablet formulations of the present invention.
The film coating agents that that can be used for flm coating of the film coated tablet formulations of the present invention can be selected from a group comprising cellulose derivatives such as hydroxypropyl cellulose, hydroxypropyl methyl cellulose, hydroxymethyl cellulose, ethyl cellulose, methyl hydroxyethyl cellulose and sodium carboxymethyl cellulose;
synthetic polymers such as polyvinyl acetal diethyl amino acetate, aminoalkyl methacrylate copolymers and polyvinylpyrrolidone; polysaccharides such as pullulan; titanium dioxide, triacetin; black, yellow and/or red iron oxides or combinations thereof.
The formulations of the present invention can optionally comprise at least another active agent.
The other active agent that can be used in the formulations can be selected from antacid, anticholinergic, antispasmodic, antiemetic, antibiotic, antipropulsive, antiallergic, antidiarrheal, antiobesity, antithrombotic, antifibrinolytic, antianemic, antihypertensive, antifungal, antipruritic, antipsoriatic, antibiotic, antiseptic, antiacne, antibacterial, antimycotic, anti-dementia, antiviral, antineoplastic, antiarrhythmic, antiadrenergic, antiepileptic,- anti- parkinson, antiprotozoal, anthelmintic, anti-inflammatory, diuretic, laxative, sulphonamide, imidazole, corticosteroid, thiazolidinedione, biguanide, immunostimulant, immunosuppressant, myorelaxant, analgesic, psycholeptic, psychoanaleptic peripheral vasodilator, beta blocker, calcium channel blocker and lipid modifying agents; alpha- glucosidase inhibitors, aldose reductase inhibitors, ACE inhibitors; multivitamin and minerals, vitamin A, vitamin D and its analogues, vitamin Bis vitamin C, vitamin E, vitamin B3, vitamin B5, vitamin B6> vitamin B7, vitamin B9, vitamin B12, vitamin B2> vitamin K, calcium, potassium, sodium, zinc, magnesium, fluoride, selenium or binary, ternary etc. combinations thereof. -
The other active agent or active agent group preferred for the formulations of the present invention is at least one anti-dementia agent and said anti-dementia agents are selected from a group comprising donepezil, galantamine, memantine, rivastigmine, ginkgo biloba extract, tacrine and or their pharmaceutically acceptable salts, enantiomers, hydrates, anhydrates etc. derivatives or binary or ternary combinations thereof.
In another aspect, the present invention presents a method for production of idebenone tablet formulations.
A characteristic feature of the formulations of the present invention is that said formulations are produced by wet granulation method.
Said production method comprises the steps of mixing the active agent or if available at least one other active agent with lactose monohydrate and at least another excipient; wet- granulating the mixture; drying and sieving the granules; adding at least another
pharmaceutically acceptable excipient into the dried granules; compressing the final mixture in tablet form and film-coating the obtained tablet.
The film coated idebenone tablet formulations of the present invention are used in the treatment of cerebral arteriosclerosis, symptoms following stroke and cerebral hemorrhage, age-associated cognitive decline, chronic cerebrovascular disease, multi-infarct dementia and mild and moderate Alzheimer's type dementia and frailty, speech disorders, memory loss, short attention span associated with these diseases, symptoms of vascular and degenerative cerebral pathologies such as psychomotor activity and depression.
There are examples given below for these formulations. The invention cannot be restricted to these examples.
Example. Film Coated Idebenone Formulation
Production Method:
Idebenone, diluent and lactose monohydrate are mixed. The mixture is wet-granulated with a granulation solution comprising the binder and at least one solvent. The granules are dried and sieved. The disintegrant is added to the obtained dry granules and they are mixed. The mixture is treated with the lubricant. The final mixture is compressed in tablet form and the tablets are coated with film.
Claims
1. Film coated tablet formulations comprising idebenone as the active agent.
2. The film coated tablet formulations according to claim 1 , characterized in that said formulations comprise idebenone in the range of 1% and 50% by weight.
3. The film coated tablet formulations according to claims 1-2, characterized in that said formulations comprise idebenone in the range of 1% and 45% by weight.
4. The film coated tablet formulations according to claims 1-3, characterized in that said formulations comprise idebenone in the range of 1% and 40% by weight.
5. The film coated tablet formulations according to any- preceding claims, -characterized - - in that the active agent idebenone in said formulations is in form of idebenone or a pharmaceutically acceptable salt, racemate, solvate, hydrate, arihydrate, different polymorphic form and amorphous form of idebenone or- combinations thereof
6. The film coated tablet formulations according to any preceding claims, characterized in that said formulations comprise at least one pharmaceutically acceptable excipient in addition to the active agent selected form a group comprising disintegrant, diluent, lubricant, glidant, binder, effervescent couple composed of at least one effervescent acid and at least one effervescent base, coloring agent, pH regulating agent, surfactant, stabilizing agent, sweetener and/or taste regulating agent, flavoring agent.
7. The film coated tablet formulations according to claim 6, characterized in that said
formulations comprise at least one filling agent selected from a group comprising calcium carbonate, dibasic calcium phosphate, tribasic calcium phosphate, calcium sulfate, microcrystalline cellulose, dextrose, fructose, lactitol, lactose or pharmaceutically acceptable derivatives thereof, magnesium carbonate, magnesium oxide, maltitol, maltodextrin, maltose, mannitol, simethicone, sorbitol, starch, sodium chloride, sucrose, talc, xylitol. - - - - -
8. The film coated tablet formulation according to- claim 7? characterized in that said
formulations comprise lactose or a pharmaceutically acceptable derivative thereof as the filling agent at least at 50% by weight- · - - ■ ' . · ■ ■ - · · ·
9. The film coated tablet formulation according to claim 8, characterized in that said
formulations comprise lactose or a pharmaceutically acceptable derivative thereof as the filling agent in the range of 50% and 85% by weight.
10. The film coated tablet formulation according to claim 9, characterized in that said formulations comprise lactose or a pharmaceutically acceptable derivative thereof as the filling agent in the range of 50% and 80% by weight.
11. The film coated tablet formulation according to claims 8-10, characterized in that the ratio of lactose or a pharmaceutically acceptable derivative thereof and idebenone to each other is in the range of 1.5 and 10 by weight.
12. The film coated tablet formulation according to claims 1 1, characterized in that the ratio of lactose or a pharmaceutically acceptable derivative thereof and idebenone to each other is in the range of 2 and 10 by weight.
13. The film coated tablet formulation according to claims 12, characterized in that the ratio of lactose or a pharmaceutically acceptable derivative thereof and- idebenone to each other is in the range of 2.5 and 10 by weight. · · · ·· — ·
14. The film coated tablet formulation according to claims 7-13, characterized in that lactose or a pharmaceutically acceptable derivative thereof used in said formulations as the filling agent is lactose, lactose monohydrate or lactose anhydrate. -■ . _
15. The film coated tablet formulation according to claims 14, characterized in that lactose or a pharmaceutically acceptable derivative thereof used in said formulations as the filling agent is lactose monohydrate.
16. The film coated tablet formulation according to any preceding claims, characterized in that said formulations optionally comprise at least another active agent.
17. The film coated tablet formulation according to claim 16, characterized in that at least another active agent that can be used in said formulations is at least one anti-dementia agent.
18. The film coated tablet formulation according to claim 17, characterized in that at least one anti-dementia agent that can be used in said formulations is selected from a group comprising donepezil, galantamine, rivastigmine, ginkgo biloba extract, tacrine and/or their pharmaceutically acceptable salts, enantiomers, hydrates, anhydrates etc. derivatives or binary or ternary combinations thereof,
19. A production method of film coated tablet formulations according to claim 1, characterized in that said method is wet-granulation method.
20. The production method according to claim 19, characterized in that said method comprises the steps of mixing the active agent and if available at least one other active agent with lactose monohydrate and at least another exeipient; wet- granulating the mixture; drying and sieving the granules; adding at least another pharmaceutically
014/035356 acceptable excipient into the dried granules; compressing the final mixture in tablet form and film-coating the obtained tablet.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| TR2012/09943 | 2012-08-31 | ||
| TR201209943 | 2012-08-31 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2014035356A1 true WO2014035356A1 (en) | 2014-03-06 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/TR2013/000283 WO2014035356A1 (en) | 2012-08-31 | 2013-08-29 | Tablet formulations comprising a quinone derivative active agent |
Country Status (1)
| Country | Link |
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| WO (1) | WO2014035356A1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9750705B2 (en) | 2012-08-31 | 2017-09-05 | The Regents Of The University Of California | Agents useful for treating obesity, diabetes and related disorders |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0629400A1 (en) * | 1993-06-18 | 1994-12-21 | Takeda Chemical Industries, Ltd. | Idebenone compositions for treating Alzheimer's disease |
| EP0788793A1 (en) * | 1996-02-01 | 1997-08-13 | Takeda Chemical Industries, Ltd. | Idebenone for the treatment of dementia |
| WO1998002149A2 (en) * | 1996-07-11 | 1998-01-22 | Takeda Chemical Industries, Ltd. | Use of idebenone and analogues against beta amyloid induced cytotoxicity |
| US5962535A (en) * | 1997-01-17 | 1999-10-05 | Takeda Chemical Industries, Ltd. | Composition for alzheimer's disease |
| EP2108366A1 (en) * | 2008-04-09 | 2009-10-14 | Santhera Pharmaceuticals (Schweiz) AG | Quinone derivative 2,3-dimethoxy-5-methyl-6-(10-hydroxydecyl)-1,4-benzoquinone for the treatment of respiratory illness in muscular dystrophy |
-
2013
- 2013-08-29 WO PCT/TR2013/000283 patent/WO2014035356A1/en active Application Filing
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0629400A1 (en) * | 1993-06-18 | 1994-12-21 | Takeda Chemical Industries, Ltd. | Idebenone compositions for treating Alzheimer's disease |
| EP0788793A1 (en) * | 1996-02-01 | 1997-08-13 | Takeda Chemical Industries, Ltd. | Idebenone for the treatment of dementia |
| WO1998002149A2 (en) * | 1996-07-11 | 1998-01-22 | Takeda Chemical Industries, Ltd. | Use of idebenone and analogues against beta amyloid induced cytotoxicity |
| US5962535A (en) * | 1997-01-17 | 1999-10-05 | Takeda Chemical Industries, Ltd. | Composition for alzheimer's disease |
| EP2108366A1 (en) * | 2008-04-09 | 2009-10-14 | Santhera Pharmaceuticals (Schweiz) AG | Quinone derivative 2,3-dimethoxy-5-methyl-6-(10-hydroxydecyl)-1,4-benzoquinone for the treatment of respiratory illness in muscular dystrophy |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9750705B2 (en) | 2012-08-31 | 2017-09-05 | The Regents Of The University Of California | Agents useful for treating obesity, diabetes and related disorders |
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