US20020031547A1 - Immediately disintegrable medicinal composition - Google Patents
Immediately disintegrable medicinal composition Download PDFInfo
- Publication number
- US20020031547A1 US20020031547A1 US09/331,235 US33123599A US2002031547A1 US 20020031547 A1 US20020031547 A1 US 20020031547A1 US 33123599 A US33123599 A US 33123599A US 2002031547 A1 US2002031547 A1 US 2002031547A1
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- United States
- Prior art keywords
- solution
- pharmaceutical composition
- alkali
- weak
- strong acid
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
-
- 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
- A61K9/2009—Inorganic compounds
-
- 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
- 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
-
- 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
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1617—Organic compounds, e.g. phospholipids, fats
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin
Definitions
- This invention relates to a pharmaceutical composition which comprises a sparingly soluble medicament held on a water soluble polymer as a solid dispersion and exhibits rapid disintegration.
- Known processes for improving solubility and absorption of a sparingly soluble medicament include a process of finely dividing the medicament, a process for forming a solid dispersion, and the like.
- the process for forming a solid dispersion is considered to be generally usable in practice for the improvement of solubility and absorption of a sparingly soluble medicament (cf. an examined Japanese patent publication 59-48810 corresponding to U.S. Pat. No. 4,673,564).
- the present inventors examined the disintegrable property of the preparation, which was obtained by adding to a composition having a newly developed sparingly soluble medicament held on a polymer base as a solid dispersion, with croscarmellose sodium which was ordinarily used as a general-purpose strong disintegrant, carboxymethylcellulose calcium, starch, low-substituted hydroxypropyl cellulose or the like. As a result, it was found that such a disintegrant could not impart a sufficient disintegrating property to the preparation.
- a disintegrant used for a preparation having a sparingly soluble medicament held on a polymer base as a solid dispersion can impart the preparation with a desired disintegrable property if it is a salt which comprises an alkali and a weak or strong acid and has an endothermic standard enthalpy of solution or heat of solution, not being limited to sodium bicarbonate. Based on this finding, the present invention was accomplished. The disintegrating mechanism upon the addition of the such a substance has not been made clear yet.
- thermodynamic effects suppress the gelation of a water-soluble polymer and, moreover, the suppression of gelation by salting-out effects of the substance having an endothermic standard enthalpy of solution accelerates the disintegration.
- the present invention relates to a rapidly disintegrable pharmaceutical composition which comprises a sparingly soluble medicament held on a gel-forming water-soluble polymer as a solid dispersion, wherein it contains a salt substance that comprises an alkali and a weak or strong acid and has an endothermic standard enthalpy of solution or heat of solution.
- the present invention also relates to a rapidly disintegrable pharmaceutical composition which comprises a surfactant and a sparingly soluble medicament held on a gel-forming water-soluble polymer as a solid dispersion, wherein it contains a salt substance that comprises an alkali and a weak or strong acid and has an endothermic standard enthalpy of solution or heat of solution.
- a pharmaceutical preparation which comprises 4′-(2-methyl-1,4,5,6-tetrahydroimidazo [4,5-d][1]benzoazepine-6-carbonyl)-2-phenylbenzanilide or a salt thereof and a pharmaceutical carrier that exhibits the dissolution of 75% of said medicament within 15 minutes when a test is performed using 500 ml of the first fluid (pH 1.2) at 100 r.p.m. in accordance with the second method (paddle method) for dissolution specified in Japanese Pharmacopoeia, 13th Edition.
- standard enthalpy of heat means a dissolving enthalpy (kJ/mol) at the time when an aqueous solution of standard conditions is produced from 1 mole of a substance under standard conditions.
- the present invention in addition to the embodiment of the present invention which comprises a salt substance which comprises an alkali and a weak or strong acid, has disintegration improving effects, and has an endothermic standard enthalpy of solution or heat of solution, the present invention embrace an embodiment which further comprises an ordinarily used disintegrant.
- the present invention also embraces an embodiment within an extent not impairing the object of the present invention, more specifically, the embodiment which further comprises an organic acid such as citric acid within an extent not affecting the pH of digestive tracts.
- the sparingly soluble medicament to be used in the present invention is not particularly limited. Its examples include those which show a solubility of 100 ml or more, preferably 1,000 ml or more, more preferably 10,000 ml of more, as the volume of solvent required for dissolving 1 g of each medicament, which is calculated by powdering the medicament, putting the powder into a solvent such as water, the first fluid or the second fluid and then measuring the solubility within 30 minutes when the suspension is vigorously shaken for 30 seconds at 20 ⁇ 5° C. at intervals of 5 minutes.
- the first fluid and second fluid as used herein are specified in the disintegration test of Japanese Pharmacopoeia, 13th Edition.
- the first fluid is an aqueous solution having a pH value of about 1.2 prepared by filling up 2 g of sodium chloride and 7.0 ml of hydrochloric acid to 1,000 ml with water
- the second fluid is an aqueous solution having a pH value of about 6.8 prepared by filling up 250 ml of 0.2 M potassium dihydrogenphosphate aqueous solution and 118 ml of 0.2 N sodium hydroxide aqueous solution to 1,000 ml with water.
- the sparingly soluble medicament include central nervous system drugs, circulatory organ system drugs, respiratory organ system drugs, digestive organ system drugs, antibiotics, chemotherapeutic agents, metabolic system drugs and vitamin drugs, all of which being sparingly soluble.
- a medicament which requires fast-acting property can be cited as a preferred example of the sparingly soluble medicament to be used in the present invention.
- Its illustrative examples include 4′-(2-methyl-1,4,5,6-tetrahydroimidazo [4,5-d][1] benzoazepine-6-carbonyl)-2-phenylbenzanilide or a salt thereof which is a known compound disclosed in International Publication 95/03305 (to be referred simply to as “Compound A” hereinafter in some cases, and its hydrochloride as “Compound A1”), (Z)-4′-[[4,4-difluoro-5-[(4-dimethylaminopiperidino) carbonyl]methylene]-2,3,4,5-tetrahydro-1H-1-benzoazepin-1-yl]carbonyl]-2-phenylbenzanilide or a salt thereof which is a known compound disclosed in International Publication 95/06035 and 1-[2,3-dihydr
- the Compound A is created by the inventors in the company of the present applicant, which has excellent antagonism for arginine vasopressin V1 and/or V2 receptor. Based on the profile of this function, it shows water diuretic action, urea excretion enhancing action, factor VIII secretion inhibition action, vasodilation action, cardiac function acceleration action, mesangial cell contraction action, mesangial cell growth inhibition action, hepatic gluconeogenesis action, platelet agglutination inhibition action, aldosterone secretion inhibition action, endothelin production inhibition action, central buffer controlling action, renin secretion controlling action, memory controlling action, body temperature controlling action and prostaglandin production controlling action, is useful as characteristic water diuretic agent, urea excretion enhancing agent, vasodilator drug, hypotensive drug, anti-cardiac failure agent, anti-renal failure agent and blood coagulation inhibitor and is effective in preventing and/or treating diseases such as
- a time required for the dissolution of 75% of Compound A is within 10 minutes.
- the carrier for the preparation is not particularly limited as long as it shows such dissolution behavior.
- the amount of Compound A is not particularly limited as long as it is a pharmacological amount ordinarily used for the treatment.
- the gel-forming water-soluble polymer usable in the present invention is not particularly limited as long as Compound A can generally be held on it as a solid dispersion.
- Specific examples of the cellulose derivative include hydroxypropylmethylcellulose (for example, “TC-5E”, “Metolose 90”, “Metolose 65SH”, each trade name; produced by Shin-Etsu Chemical Co., Ltd.), hydroxypropylcellulose (for example, “Nisso HPC”, trade name; produced by Nippon Soda Co., Ltd.), methyl cellulose (for example, “Metolose SM”, trade name; produced by Shin-Etsu Chemical Co., Ltd.), and hydroxyethylcellulose (“NATROSOL”, trade name; produced by Hercules Japan, Ltd.). More preferred is hydroxypropylmethylcellulose.
- These gel-forming water-soluble polymers can be used either singly or in combination.
- a surfactant may be added.
- the surfactant is not particularly limited as long as it is pharmaceutically acceptable.
- examples thereof include anionic surfactants such as sodium alkylsulfate and nonionic surfactants such as polyoxyethylene sorbitan fatty acid esters (for example, Polysorbate 80; “Rheodol TW-0120”, trade name; produced by Kao Corp.), polyoxyethylene fatty acid esters and polyoxyethylene castor oil derivatives (for example, polyoxyethylene hydrogenated castor oil (60); “HCO-60”, trade name; produced by Nikko Chemicals Co., Ltd.). These surfactants may be used either singly or in combination.
- the gel-forming water-soluble polymer is added in an amount of 0.5 to 20 parts by weight, preferably 1 to 10 parts by weight, more preferably 1 to 5 parts by weight, based on 1 part by weight of the sparingly soluble medicament.
- the surfactant is added in an amount of 0.1 to 3 parts by weight, preferably 0.2 to 1.5 parts by weight, more preferably 0.25 to 1.25 parts by weight based on 1 part by weight of the sparingly soluble medicament.
- Examples of the salt substance used in the present invention which comprises an alkali and a weak or strong acid and has an endothermic standard enthalpy of solution or heat of solution (which may hereinafter be abbreviated as “disintegrable improver”, simply) include sodium bicarbonate (19.1 kJ/mol, 4.3 kcal/mol), potassium bicarbonate (5.3 kcal/mol), potassium sulfate (23.7 kJ/mol, 6.38 kcal/mol), potassium chloride (17.2 kJ/mol, 4.19 kcal/mol), sodium chloride (3.9 kJ/mol, 1.18 kcal/mol) and potassium dihydrogenphosphate (19.6 kJ/mol, 4.85 kcal/mol) .
- sodium bicarbonate preferred are sodium bicarbonate, potassium bicarbonate, potassium sulfate and potassium dihydrogenphosphate.
- sodium bicarbonate and/or potassium bicarbonate are more preferred, and sodium bicarbonate is still more preferred.
- These disintegrable improvers may be used either singly or in combination.
- the amount of the disintegrable improver used in the present invention is not particularly limited as long as it is a pharmaceutically acceptable amount. It is preferably added in an amount of at least 0.1 part by weight, more preferably 0.1 to 6 parts by weight, still more preferably 0.3 to 1 part by weight based on 1 part by weight of the gel-forming water-soluble polymer. Amounts smaller than 0.1 part by weight show small effects, and it is desired to suppress the amount of an excipient upon formulation.
- the sparingly soluble medicament, gel-forming water-soluble polymer, surfactant and disintegrable improver are added in amounts (wt./wt. %) of 1 to 30%, 3 to 60%, 0 to 20% and 3 to 50%, respectively, preferably 3 to 15%, 10 to 50%, 0 to 10% and 5 to 30%, respectively, each based on the total amount of the preparation.
- a preferred pharmaceutical composition or pharmaceutical preparation according to the present invention is that comprising hydroxypropylmethylcellulose as the gel-forming water-soluble polymer, sodium bicarbonate as a salt substance which comprises an alkali and a weak or strong acid and has an endothermic standard enthalpy of solution or heat of solution, and optional a polyoxyethylene sorbitan fatty acid ester as a surfactant.
- a composition which comprises a sparingly soluble medicament held on a gel-forming water-soluble polymer as a solid dispersion and a solid dispersion which comprises a sparingly soluble medicament held on a gel-forming water-soluble polymer containing a surfactant can be prepared in a known manner.
- a sparingly soluble medicament, a surfactant, etc. can be prepared by suspending or dissolving Compound A and a gel-forming water-soluble polymer and an optional surfactant in water or an organic solvent (e.g., a lower alcohol such as methanol or ethanol, or a halogen-based organic solvent such as dichloromethane) and then spray drying the solution or suspension.
- the solid dispersion may be prepared by the step of spraying the solution or suspension to an excipient, and then granulating.
- the granulation can be carried out in a known manner, for example, by a fluidized bed granulator (manufactured by Okawara Seisakujo), a vertical mixer (manufactured by San-Ei Seisakujo) or an agitating granulator (manufactured by Fukae Kogyo).
- a fluidized bed granulator granulation is carried out by generally operable conditions, for example, at a spray pressure of 0.3 to 3 kg/cm 2 and product temperature of 20 to 45° C. until the granule size reaches the desired level.
- the pharmaceutical preparation of the present invention can be used in the form of tablets, granules or capsules.
- compression-molded tablets and capsules having a solid dispersion filled therein exhibit more desirable effects of the present invention.
- Preparations in such forms can be prepared in a known manner.
- tablets can be prepared on a single punch tabletting machine (manufactured by Kikusui Seisakujo) or rotary tabletting machine (manufactured by Hata Seisakujo).
- the molding pressure upon tabletting may be set as desired based on the hardness, disintegrable property, etc. of the molded product and is not particularly limited. Examples of the molding pressure include 0.3 ton/punch to 1 ton/punch.
- Such a pharmaceutical preparation can be prepared in a known manner by using, for example, as an additive, an excipient such as lactose, corn starch, light anhydrous silicic acid, microcrystalline cellulose or crystalline cellulose (“Avicel PH102”, trade name; product of Asahi Kasei); a binder such as a starch, methylcellulose, carboxymethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, polyvinyl pyrrolidone, gum arabic powder, gelatin or pullulan; a disintegrant such as croscarmellose sodium (“Ac-Di-Sol”, trade name; produced by Asahi Kasei), carboxymethylcellulose calcium, starch or low-substituted hydroxypropylcellulose; a surfactant such as “Polysorbate 80” (produced by Kao Astra Co., Ltd.), polyoxyethylene hydrogenated castor oil (“HCO-60”, trade name; product by Nikko Chemicals) or “PLURON
- polyoxypropylene copolymerized substance produced by Asahi Denka Kogyo K.K.); antioxidant such as sodium sulfite or sodium ascorbate; lubricant such as magnesium stearate, calcium stearate, talc, sucrose fatty acid ester, polyethylene glycol or stearic acid; sour agent such as citric acid, tartaric acid or malic acid; artificial sweetener such as sodium saccharin, dipotassium glycyrrhizinate, aspartame, stevia or somatin; flavor such as lemon, lemon lime, orange or menthol; colorant such as Food Yellow 5, Food Red 2 or Food Blue 2; and stabilizer.
- antioxidant such as sodium sulfite or sodium ascorbate
- lubricant such as magnesium stearate, calcium stearate, talc, sucrose fatty acid ester, polyethylene glycol or stearic acid
- sour agent such as citric acid, tartaric acid or mal
- the solid dispersion in the tablet or granule preparation, or the tablet or granule preapration itself may be coated in a known manner.
- the coating agent include hydroxypropylcellulose, ethylcellulose, hydroxymethylcellulose and hydroxypropylcellulose. They may be used either singly or in combination and coating of a single layer or two or more layers is possible.
- the coating is carried out in a known manner, for example, by the pan coating method, fluidized bed coating method or tumbling coating method through spraying a dispersion or solution of a coating base in water or an organic solvent.
- a 200 mg portion of the solid dispersion obtained above (in the preparation of a solid dispersion of Compound B) and 75 mg of sodium bicarbonate were uniformly mixed, and the resulting mixture was formed into tablets each having a weight of 275 mg and a diameter of 7.5 mm by an oil press under a tabletting pressure of 500 kg/punch.
- the result of the dissolution test was 15 minutes.
- a 200 mg portion of the solid dispersion obtained above (in the preparation of a solid dispersion of Compound B) and 100 mg of sodium bicarbonate were uniformly mixed, and the resulting mixture was formed into tablets each having a weight of 300 mg and a diameter of 7.5 mm by an oil press under a tabletting pressure of 500 kg/punch.
- the result of the dissolution test was 10 minutes.
- the pharmaceutical composition of the present invention exhibits rapid disintegration of sparingly soluble medicaments having completely different structures regardless of the presence or absence of their salts and is a medicament preparation technique having high general-purpose performance.
- the pharmaceutical composition according to the present invention exhibits rapid disintegration. Owing to rapid dissolution of a sparingly soluble medicament from the composition, good bioavailability can be attained.
- the preparation comprising the above pharmaceutical composition therefore exhibits rapid disintegration independently of the pH in the digestive tract and the medicament contained in the preparation exhibits rapid dissolution.
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
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- Inorganic Chemistry (AREA)
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Priority Applications (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US10/190,568 US6899899B2 (en) | 1996-12-25 | 2002-07-09 | Rapidly disintegrable pharmaceutical composition |
US10/998,659 US7189415B2 (en) | 1996-12-25 | 2004-11-30 | Rapidly disintegrable pharmaceutical composition |
US11/522,977 US20070014856A1 (en) | 1996-12-25 | 2006-09-19 | Rapidly disintegrable pharmaceutical composition |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP34476896 | 1996-12-25 | ||
JPP.HEI.8-344768 | 1996-12-25 |
Related Child Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US10/190,568 Continuation US6899899B2 (en) | 1996-12-25 | 2002-07-09 | Rapidly disintegrable pharmaceutical composition |
US10/998,659 Continuation US7189415B2 (en) | 1996-12-25 | 2004-11-30 | Rapidly disintegrable pharmaceutical composition |
Publications (1)
Publication Number | Publication Date |
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US20020031547A1 true US20020031547A1 (en) | 2002-03-14 |
Family
ID=18371833
Family Applications (4)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US09/331,235 Abandoned US20020031547A1 (en) | 1996-12-25 | 1997-12-24 | Immediately disintegrable medicinal composition |
US10/190,568 Expired - Fee Related US6899899B2 (en) | 1996-12-25 | 2002-07-09 | Rapidly disintegrable pharmaceutical composition |
US10/998,659 Expired - Fee Related US7189415B2 (en) | 1996-12-25 | 2004-11-30 | Rapidly disintegrable pharmaceutical composition |
US11/522,977 Abandoned US20070014856A1 (en) | 1996-12-25 | 2006-09-19 | Rapidly disintegrable pharmaceutical composition |
Family Applications After (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US10/190,568 Expired - Fee Related US6899899B2 (en) | 1996-12-25 | 2002-07-09 | Rapidly disintegrable pharmaceutical composition |
US10/998,659 Expired - Fee Related US7189415B2 (en) | 1996-12-25 | 2004-11-30 | Rapidly disintegrable pharmaceutical composition |
US11/522,977 Abandoned US20070014856A1 (en) | 1996-12-25 | 2006-09-19 | Rapidly disintegrable pharmaceutical composition |
Country Status (14)
Country | Link |
---|---|
US (4) | US20020031547A1 (fr) |
EP (2) | EP1759712A2 (fr) |
JP (1) | JP3988193B2 (fr) |
KR (1) | KR100534504B1 (fr) |
CN (1) | CN1132635C (fr) |
AR (1) | AR009438A1 (fr) |
AT (1) | ATE397459T1 (fr) |
AU (1) | AU5339798A (fr) |
CA (1) | CA2272586C (fr) |
DE (1) | DE69738755D1 (fr) |
ES (1) | ES2307303T3 (fr) |
TW (1) | TW486370B (fr) |
WO (1) | WO1998029137A1 (fr) |
ZA (1) | ZA9711508B (fr) |
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US20050143404A1 (en) * | 2003-08-28 | 2005-06-30 | Joerg Rosenberg | Solid pharmaceutical dosage formulation |
US20070141144A1 (en) * | 2004-05-28 | 2007-06-21 | Roberts Michael S | Oral delivery system |
US7235260B2 (en) | 2000-03-16 | 2007-06-26 | Pfizer Inc | Pharmaceutical compositions of a sparingly soluble glycogen phosphorylase inhibitor |
US20080248117A1 (en) * | 2005-06-09 | 2008-10-09 | Basf Aktiengesellschaft | Production of Solid Solutions Based on Poorly-Soluble Active Substances by a Short-Term Heating and Rapid Drying |
US20080287456A1 (en) * | 2004-05-28 | 2008-11-20 | Imaginot Pty Ltd | Oral Therapeutic Compound Delivery System |
US20090270463A1 (en) * | 2008-04-02 | 2009-10-29 | Astellas Pharma Inc. | Amido derivatives-contained pharmaceutical composition |
US20090311327A1 (en) * | 2005-11-28 | 2009-12-17 | Imaginot Pty Ltd | Oral Therapeutic Compound Delivery System |
US20100021393A1 (en) * | 2004-08-20 | 2010-01-28 | Abbott Laboratories | Pharmaceutical Compositions Comprising Effervescent Agents and Fenofibrate |
US20110008430A1 (en) * | 2003-08-28 | 2011-01-13 | Abbott Laboratories | Solid Pharmaceutical Dosage Form |
US20120015924A1 (en) * | 2009-03-27 | 2012-01-19 | Friesen Dwayne T | Spray-drying process |
US20120053238A1 (en) * | 2009-03-17 | 2012-03-01 | Ratiopharm Gmbh | Solid retigabine in non-crystalline form |
US20130020265A1 (en) * | 2009-11-19 | 2013-01-24 | Nippon Soda Co., Ltd. | Reduction treatment method for ballast water |
US8470347B2 (en) | 2000-05-30 | 2013-06-25 | AbbVie Deutschland GmbH and Co KG | Self-emulsifying active substance formulation and use of this formulation |
US20140024723A1 (en) * | 2012-07-17 | 2014-01-23 | Dow Global Technologies Llc | Composition comprising an organic liquid diluent and a specific hydroxypropyl methylcellulose |
US20140030346A1 (en) * | 2010-12-27 | 2014-01-30 | Masashi Konishi | Disintegrable core particle for pharmaceutical preparation |
WO2014043208A1 (fr) | 2012-09-11 | 2014-03-20 | Medivation Prostate Therapeutics, Inc. | Formulations d'enzalutamide |
US9775832B2 (en) | 2014-06-24 | 2017-10-03 | Astellas Pharma Inc. | Pharmaceutical composition for oral administration |
WO2018037310A1 (fr) | 2016-08-20 | 2018-03-01 | Ftf Pharma Private Limited | Composition pharmaceutique comprenant un inhibiteur du récepteur des androgènes |
US10583087B2 (en) | 2015-04-28 | 2020-03-10 | Astellas Pharma Inc. | Pharmaceutical composition for oral administration |
US20200261426A1 (en) * | 2017-10-31 | 2020-08-20 | Samyang Biopharmaceuticals Corporation | Oral solid dosage form composition having improved disintegration and preparation method therefor |
WO2020234448A1 (fr) | 2019-05-23 | 2020-11-26 | Helm Ag | Nanoparticules à base d'enzalutamide |
US11364203B2 (en) | 2014-10-31 | 2022-06-21 | Bend Reserch, Inc. | Process for forming active domains dispersed in a matrix |
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TW486370B (en) * | 1996-12-25 | 2002-05-11 | Yamanouchi Pharma Co Ltd | Rapidly disintegrable pharmaceutical composition |
JP2000191518A (ja) * | 1998-10-19 | 2000-07-11 | Eisai Co Ltd | 溶解性の改善された口腔内速崩壊性錠剤 |
DE19931708A1 (de) | 1999-07-08 | 2001-01-18 | Bayer Ag | Verfahren zur Herstellung schnell zerfallender, fester pharmazeutischer Zubereitungen |
ATE406885T1 (de) * | 2000-10-24 | 2008-09-15 | Ajinomoto Kk | Nateglinid enthaltende präparate |
DK1275377T3 (da) * | 2001-07-11 | 2003-10-06 | Applied Pharma Res | Granulater, der indeholder fedtopløselige stoffer, og en fremgangsmåde til fremstilling deraf |
KR20040079967A (ko) | 2002-02-01 | 2004-09-16 | 화이자 프로덕츠 인크. | 고체 약물 분산액을 함유하는 속방형 제형 |
JP4780522B2 (ja) * | 2003-11-14 | 2011-09-28 | 味の素株式会社 | フェニルアラニン誘導体の固体分散体または固体分散体医薬製剤 |
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US20080132560A1 (en) * | 2006-11-21 | 2008-06-05 | San-Laung Chow | Solid dispersion composition |
WO2010113324A1 (fr) * | 2009-04-03 | 2010-10-07 | 日医工ファーマ株式会社 | Préparation de gelée contenant de la pectine |
CN101810563B (zh) * | 2009-09-25 | 2012-04-25 | 宋洪涛 | 他克莫司眼用在体凝胶制剂及其制备方法 |
TWI564008B (zh) | 2010-09-30 | 2017-01-01 | 鹽野義製藥股份有限公司 | 難溶性藥物之溶解性改善製劑 |
CA2828946C (fr) | 2011-04-18 | 2016-06-21 | Eisai R&D Management Co., Ltd. | Agent therapeutique pour les tumeurs |
EP2714937B1 (fr) | 2011-06-03 | 2018-11-14 | Eisai R&D Management Co., Ltd. | Biomarqueurs pour la prédiction et l'estimation de la sensibilité de sujets atteints d'un cancer de la thyroïde et du rein vis-à-vis de composés lenvatinib |
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WO2014185540A1 (fr) | 2013-05-14 | 2014-11-20 | Eisai R&D Management Co., Ltd. | Biomarqueurs pour prédire et évaluer la réponse de sujets atteints de cancer de l'endomètre à des composés à base de lenvatinib |
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RU2729936C2 (ru) | 2015-06-16 | 2020-08-13 | Эйсай Ар Энд Ди Менеджмент Ко., Лтд. | Противораковое средство |
WO2019172420A1 (fr) * | 2018-03-09 | 2019-09-12 | 協和発酵キリン株式会社 | Composition pharmaceutique |
MX2021001063A (es) * | 2018-07-30 | 2021-04-12 | Chugai Pharmaceutical Co Ltd | Dispersion solida de derivado de hidantoina. |
WO2021155254A1 (fr) | 2020-01-31 | 2021-08-05 | Nanocopoeia, Llc | Microparticules de nilotinib amorphe et leurs utilisations |
IL297776A (en) | 2020-04-30 | 2022-12-01 | Nanocopoeia Llc | Orally disintegrating tablets containing an amorphous solid dispersion of nalotinib |
Family Cites Families (21)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA1146866A (fr) * | 1979-07-05 | 1983-05-24 | Yamanouchi Pharmaceutical Co. Ltd. | Procede de production d'un compose pharmaceutique a liberation continue sous forme solide |
US4255413A (en) * | 1979-10-01 | 1981-03-10 | Smithkline Corporation | Gelatin capsule dosage unit containing triamterene |
JPS56110612A (en) * | 1980-02-08 | 1981-09-01 | Yamanouchi Pharmaceut Co Ltd | Readily disintegrable and absorbable compression molded article of slightly soluble drug |
JPS5948810A (ja) | 1982-09-10 | 1984-03-21 | Sony Corp | 磁性記録体におけるデ−タのマスク及び再生方法 |
US4946686A (en) * | 1987-09-24 | 1990-08-07 | Merck & Co., Inc. | Solubility modulated drug delivery system |
DE3877331T2 (de) * | 1987-11-11 | 1993-05-27 | Pharmascience Lab | Exifon und ein wasserloesliches polymer enthaltende pharmazeutische zubereitung. |
US4964686A (en) * | 1987-12-14 | 1990-10-23 | Canon Kabushiki Kaishi | Finder optical device |
WO1989006959A1 (fr) * | 1988-02-03 | 1989-08-10 | Yoshitomi Pharmaceutical Industries, Ltd. | Preparation pharmaceutique a liberation amelioree |
JP2814513B2 (ja) | 1988-02-03 | 1998-10-22 | 吉富製薬株式会社 | 溶出性の改良された製剤組成物 |
US5211957A (en) * | 1988-03-25 | 1993-05-18 | Ciba-Geigy Corporation | Solid rapidly disintegrating dosage form |
JP2906528B2 (ja) * | 1990-02-14 | 1999-06-21 | 大正製薬株式会社 | 吸収を促進した内服用固形製剤 |
JP3240729B2 (ja) * | 1993-03-05 | 2001-12-25 | 株式会社リコー | ファクシミリ装置 |
NZ271454A (en) * | 1993-08-26 | 1997-07-27 | Yamanouchi Pharma Co Ltd | Difluoro substituted benzazepine derivatives and pharmaceutical compositions |
US5399358A (en) * | 1993-11-12 | 1995-03-21 | Edward Mendell Co., Inc. | Sustained release formulations for 24 hour release of metroprolol |
JPH08127533A (ja) * | 1994-11-01 | 1996-05-21 | Taisho Pharmaceut Co Ltd | 内服固形製剤用組成物 |
WO1996019974A1 (fr) * | 1994-12-27 | 1996-07-04 | Kanebo, Ltd. | Preparation a liberation prolongee |
JPH08231403A (ja) * | 1995-02-27 | 1996-09-10 | Yamanouchi Pharmaceut Co Ltd | アルギニンバソプレシン拮抗薬を含有する安定な水溶液 |
US5834472A (en) * | 1996-05-24 | 1998-11-10 | Schering Corporation | Antifungal composition with enhanced bioavailability |
TW486370B (en) * | 1996-12-25 | 2002-05-11 | Yamanouchi Pharma Co Ltd | Rapidly disintegrable pharmaceutical composition |
US5964686A (en) * | 1997-11-07 | 1999-10-12 | Griffin Automation, Inc. | Method for forming slotted and creased box blanks |
US6632455B2 (en) * | 1997-12-22 | 2003-10-14 | Schering Corporation | Molecular dispersion composition with enhanced bioavailability |
-
1997
- 1997-12-08 TW TW086118467A patent/TW486370B/zh active
- 1997-12-17 AR ARP970105926A patent/AR009438A1/es unknown
- 1997-12-22 ZA ZA9711508A patent/ZA9711508B/xx unknown
- 1997-12-24 CA CA002272586A patent/CA2272586C/fr not_active Expired - Fee Related
- 1997-12-24 AT AT97950375T patent/ATE397459T1/de not_active IP Right Cessation
- 1997-12-24 EP EP06023230A patent/EP1759712A2/fr not_active Withdrawn
- 1997-12-24 KR KR10-1999-7005775A patent/KR100534504B1/ko not_active IP Right Cessation
- 1997-12-24 EP EP97950375A patent/EP1008354B1/fr not_active Expired - Lifetime
- 1997-12-24 WO PCT/JP1997/004788 patent/WO1998029137A1/fr active IP Right Grant
- 1997-12-24 JP JP52983098A patent/JP3988193B2/ja not_active Expired - Fee Related
- 1997-12-24 DE DE69738755T patent/DE69738755D1/de not_active Expired - Lifetime
- 1997-12-24 CN CN97180989A patent/CN1132635C/zh not_active Expired - Fee Related
- 1997-12-24 AU AU53397/98A patent/AU5339798A/en not_active Abandoned
- 1997-12-24 ES ES97950375T patent/ES2307303T3/es not_active Expired - Lifetime
- 1997-12-24 US US09/331,235 patent/US20020031547A1/en not_active Abandoned
-
2002
- 2002-07-09 US US10/190,568 patent/US6899899B2/en not_active Expired - Fee Related
-
2004
- 2004-11-30 US US10/998,659 patent/US7189415B2/en not_active Expired - Fee Related
-
2006
- 2006-09-19 US US11/522,977 patent/US20070014856A1/en not_active Abandoned
Cited By (43)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7235260B2 (en) | 2000-03-16 | 2007-06-26 | Pfizer Inc | Pharmaceutical compositions of a sparingly soluble glycogen phosphorylase inhibitor |
US8470347B2 (en) | 2000-05-30 | 2013-06-25 | AbbVie Deutschland GmbH and Co KG | Self-emulsifying active substance formulation and use of this formulation |
US8333990B2 (en) | 2003-08-28 | 2012-12-18 | Abbott Laboratories | Solid pharmaceutical dosage form |
US8309613B2 (en) | 2003-08-28 | 2012-11-13 | Abbvie Inc. | Solid pharmaceutical dosage form |
US8399015B2 (en) | 2003-08-28 | 2013-03-19 | Abbvie Inc. | Solid pharmaceutical dosage form |
US8377952B2 (en) | 2003-08-28 | 2013-02-19 | Abbott Laboratories | Solid pharmaceutical dosage formulation |
US20110008430A1 (en) * | 2003-08-28 | 2011-01-13 | Abbott Laboratories | Solid Pharmaceutical Dosage Form |
US20110015216A1 (en) * | 2003-08-28 | 2011-01-20 | Abbott Laboratories | Solid Pharmaceutical Dosage Form |
US20050143404A1 (en) * | 2003-08-28 | 2005-06-30 | Joerg Rosenberg | Solid pharmaceutical dosage formulation |
US8691878B2 (en) | 2003-08-28 | 2014-04-08 | Abbvie Inc. | Solid pharmaceutical dosage form |
US8268349B2 (en) | 2003-08-28 | 2012-09-18 | Abbott Laboratories | Solid pharmaceutical dosage form |
US20080287456A1 (en) * | 2004-05-28 | 2008-11-20 | Imaginot Pty Ltd | Oral Therapeutic Compound Delivery System |
US20070141144A1 (en) * | 2004-05-28 | 2007-06-21 | Roberts Michael S | Oral delivery system |
US8216610B2 (en) | 2004-05-28 | 2012-07-10 | Imaginot Pty Ltd. | Oral paracetamol formulations |
US20100021393A1 (en) * | 2004-08-20 | 2010-01-28 | Abbott Laboratories | Pharmaceutical Compositions Comprising Effervescent Agents and Fenofibrate |
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US9757455B2 (en) | 2005-11-28 | 2017-09-12 | Johnson & Johnson Consumer Inc. | Oral therapeutic compound delivery system |
US20090311327A1 (en) * | 2005-11-28 | 2009-12-17 | Imaginot Pty Ltd | Oral Therapeutic Compound Delivery System |
US20090270463A1 (en) * | 2008-04-02 | 2009-10-29 | Astellas Pharma Inc. | Amido derivatives-contained pharmaceutical composition |
US9050326B2 (en) | 2008-04-02 | 2015-06-09 | Astellas Pharma Inc. | Amido derivatives-contained pharmaceutical composition |
US20120053238A1 (en) * | 2009-03-17 | 2012-03-01 | Ratiopharm Gmbh | Solid retigabine in non-crystalline form |
US10300443B2 (en) | 2009-03-27 | 2019-05-28 | Bend Research, Inc. | Spray-drying process |
US9724664B2 (en) * | 2009-03-27 | 2017-08-08 | Bend Research, Inc. | Spray-drying process |
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US20120015924A1 (en) * | 2009-03-27 | 2012-01-19 | Friesen Dwayne T | Spray-drying process |
US20130020265A1 (en) * | 2009-11-19 | 2013-01-24 | Nippon Soda Co., Ltd. | Reduction treatment method for ballast water |
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US20140030346A1 (en) * | 2010-12-27 | 2014-01-30 | Masashi Konishi | Disintegrable core particle for pharmaceutical preparation |
US20140024723A1 (en) * | 2012-07-17 | 2014-01-23 | Dow Global Technologies Llc | Composition comprising an organic liquid diluent and a specific hydroxypropyl methylcellulose |
EP3725778A1 (fr) | 2012-09-11 | 2020-10-21 | Medivation Prostate Therapeutics LLC | Formulations d'enzalutamide |
US11839689B2 (en) | 2012-09-11 | 2023-12-12 | Astellas Pharma Inc. | Formulations of enzalutamide |
EP4324527A2 (fr) | 2012-09-11 | 2024-02-21 | Medivation Prostate Therapeutics LLC | Formulations d'enzalutamide |
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EP3971167A1 (fr) | 2012-09-11 | 2022-03-23 | Medivation Prostate Therapeutics LLC | Formulations d'enzalutamide |
WO2014043208A1 (fr) | 2012-09-11 | 2014-03-20 | Medivation Prostate Therapeutics, Inc. | Formulations d'enzalutamide |
US9775832B2 (en) | 2014-06-24 | 2017-10-03 | Astellas Pharma Inc. | Pharmaceutical composition for oral administration |
US11364203B2 (en) | 2014-10-31 | 2022-06-21 | Bend Reserch, Inc. | Process for forming active domains dispersed in a matrix |
US10583087B2 (en) | 2015-04-28 | 2020-03-10 | Astellas Pharma Inc. | Pharmaceutical composition for oral administration |
WO2018037310A1 (fr) | 2016-08-20 | 2018-03-01 | Ftf Pharma Private Limited | Composition pharmaceutique comprenant un inhibiteur du récepteur des androgènes |
US20200261426A1 (en) * | 2017-10-31 | 2020-08-20 | Samyang Biopharmaceuticals Corporation | Oral solid dosage form composition having improved disintegration and preparation method therefor |
JP7458317B2 (ja) | 2017-10-31 | 2024-03-29 | サムヤン、ホールディングス、コーポレーション | 崩壊が改善された経口用固形製剤組成物及びその製造方法 |
US11980610B2 (en) * | 2017-10-31 | 2024-05-14 | Samyang Holdings Corporation | Oral solid dosage form composition having improved disintegration and preparation method therefor |
WO2020234448A1 (fr) | 2019-05-23 | 2020-11-26 | Helm Ag | Nanoparticules à base d'enzalutamide |
Also Published As
Publication number | Publication date |
---|---|
ES2307303T3 (es) | 2008-11-16 |
CN1241946A (zh) | 2000-01-19 |
ATE397459T1 (de) | 2008-06-15 |
EP1759712A2 (fr) | 2007-03-07 |
ZA9711508B (en) | 1998-06-24 |
KR100534504B1 (ko) | 2005-12-08 |
DE69738755D1 (de) | 2008-07-17 |
US20050095289A1 (en) | 2005-05-05 |
TW486370B (en) | 2002-05-11 |
KR20000062327A (ko) | 2000-10-25 |
US6899899B2 (en) | 2005-05-31 |
CA2272586C (fr) | 2005-11-22 |
JP3988193B2 (ja) | 2007-10-10 |
AR009438A1 (es) | 2000-04-12 |
EP1008354A1 (fr) | 2000-06-14 |
EP1008354A4 (fr) | 2006-02-01 |
AU5339798A (en) | 1998-07-31 |
US7189415B2 (en) | 2007-03-13 |
CA2272586A1 (fr) | 1998-07-09 |
CN1132635C (zh) | 2003-12-31 |
WO1998029137A1 (fr) | 1998-07-09 |
EP1008354B1 (fr) | 2008-06-04 |
US20070014856A1 (en) | 2007-01-18 |
US20030003146A1 (en) | 2003-01-02 |
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