CA2452386A1 - Granulates containing liposoluble substances and a process for the preparation thereof - Google Patents
Granulates containing liposoluble substances and a process for the preparation thereof Download PDFInfo
- Publication number
- CA2452386A1 CA2452386A1 CA002452386A CA2452386A CA2452386A1 CA 2452386 A1 CA2452386 A1 CA 2452386A1 CA 002452386 A CA002452386 A CA 002452386A CA 2452386 A CA2452386 A CA 2452386A CA 2452386 A1 CA2452386 A1 CA 2452386A1
- Authority
- CA
- Canada
- Prior art keywords
- substance
- granulate
- water
- weight
- liposoluble
- 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.)
- Granted
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
- A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
-
- 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
- A61K9/1617—Organic compounds, e.g. phospholipids, fats
- A61K9/1623—Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/18—Feminine contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Abstract
A process is described for the preparation of granulates that contain liposoluble and hydrophobic substances, preferably steroidal substances, and that exhibit rapid and excellent water-dispersibility. The process comprises:
a) the dispersion of substance (A) in water in the presence of a surfactant (B), b) the incorporation of a water-soluble polyhydroxylated solid excipient (C) in the aqueous dispersion until a granulable pasty mass is obtained and c) the granulation of the mass. The granulates so obtained are suitable for the preparation, at the time of use, of stable and homogeneous aqueous suspensions that are used for nutritional, cosmetic or, preferably, pharmaceutical purposes.
a) the dispersion of substance (A) in water in the presence of a surfactant (B), b) the incorporation of a water-soluble polyhydroxylated solid excipient (C) in the aqueous dispersion until a granulable pasty mass is obtained and c) the granulation of the mass. The granulates so obtained are suitable for the preparation, at the time of use, of stable and homogeneous aqueous suspensions that are used for nutritional, cosmetic or, preferably, pharmaceutical purposes.
Claims (22)
1. A process for preparing a granulate that exhibits rapid and excellent water-dispersibility and that contains liposoluble and hydrophobic substances, having a water-solubility at 20°C of less than 20 µml, which process comprises:
a) the dispersion of substance (A) in water in the presence of a surfactant (B), b) the incorporation of a water-soluble polyhydroxylated solid excipient (C) in the aqueous dispersion until a granulable pasty mass is obtained and c) the granulation of the mass, wherein the surfactant (B) and the polyhydroxylated solid excipient (C) are present in amounts by weight of, respectively, from 0.013 to 0.7 of (B) and from 1 to 6 of (C), per unit of liposoluble substance (A).
a) the dispersion of substance (A) in water in the presence of a surfactant (B), b) the incorporation of a water-soluble polyhydroxylated solid excipient (C) in the aqueous dispersion until a granulable pasty mass is obtained and c) the granulation of the mass, wherein the surfactant (B) and the polyhydroxylated solid excipient (C) are present in amounts by weight of, respectively, from 0.013 to 0.7 of (B) and from 1 to 6 of (C), per unit of liposoluble substance (A).
2. A process according to claim 1, wherein the substance (A) is a steroidal substance, preferably megestrol acetate.
3. A process according to claim 1, wherein the surfactant (B) is a polysorbate, preferably polysorbate 80.
4. A process according to claim 1, wherein the dispersion of the liposoluble substance (A) in water is effected at a temperature of from 20°C to 60°C, preferably from 25°C to 40°C.
5. A process according to claim 1, wherein the water-soluble polyhydroxylated solid excipient (C) is selected from mannitol, sorbitol, lactose and fructose and mixtures thereof.
6. A process according to claim 1, wherein the surfactant (B) and the polyhydroxylated solid excipient (C) are present, in amounts by weight, of from 0.02 to 0.33 of (B) and from 3 to 5 of (C), per unit of liposoluble substance (A).
7. A process according to claim 1, wherein the amount of water, by weight, relative to substance (A), is from 0.2 to 1, preferably from 0.5 to 0.7.
8. A granulate obtainable according to claims 1 to 7.
9. A granulate according to claim 8, having a content of substance (A) of from 5 to 50% by weight, preferably from 15 to 25% by weight.
10. A pharmaceutical composition comprising a granulate according to claim 8.
11. A pharmaceutical composition according to claim 10, in the form of an aqueous dispersion.
12. A pharmaceutical composition according to claim 10, in the form of a packet, an effervescent packet, a syrup prepared at the time of use, a tablet, an effervescent tablet and a quick-dissolving sublingual tablet.
13. A process for the preparation of an aqueous dispersion according to claim 11, characterized in that the granulate is mixed with at least 80 ml of water per gram of granulate and is agitated until complete dispersion has occurred.
14. A granulate comprising a liposoluble and hydrophobic substance (A), having a water-solubility at 20°C of less than 20 µg/ml, a surfactant (B), and a water soluble polyhydroxylated solid excipient (C) in amounts by weight of, respectively, from 0.013 to 0.7 of (B) and from 1 to 6 of (C), per unit of liposoluble substance (A).
15. A granulate according to claim 14 characterized in that said liposoluble substance (A) is a steroidal substance.
16. A granulate according to claim 14 characterized in that said liposoluble substance (A) is megestrol acetate.
17. A granulate according to claims 14 to 16 characterized in that the surfactant (B) is a polysorbate, preferably polysorbate 80.
18. A granulate according to claims 14 to 17 characterized in that water-soluble polyhydroxylated solid excipient (C) is selected from mannitol, sorbitol, lactose and fructose and mixtures thereof.
19. A granulate according to claims 14 to 18 wherein the surfactant (B) and the polyhydroxylated solid excipient (C) are present, in amounts by weight, of from 0.02 to 0.33 of (B) and from 3 to 5 of (C), per unit of liposoluble substance (A).
20. A granulate according to claims 14 to 19 characterized by further containing pharmaceutically acceptable excipients.
21. A granulate according to claims 14 to 20 characterized in that said liposoluble substance (A) is present in amounts of 5 to 50% by weight.
22. A granulate according to claim 21 characterized in that said liposoluble substance (A) is present in amounts of 15 to 25% by weight.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP01202657A EP1275377B1 (en) | 2001-07-11 | 2001-07-11 | Granulates containing liposoluble substances and process of preparation thereof |
| EP01202657.1 | 2001-07-11 | ||
| PCT/EP2002/007636 WO2003005989A2 (en) | 2001-07-11 | 2002-07-09 | Granulates containing liposoluble substances and a process for the preparation thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2452386A1 true CA2452386A1 (en) | 2003-01-23 |
| CA2452386C CA2452386C (en) | 2011-01-18 |
Family
ID=8180628
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2452386A Expired - Fee Related CA2452386C (en) | 2001-07-11 | 2002-07-09 | Granulates containing liposoluble substances and a process for the preparation thereof |
Country Status (21)
| Country | Link |
|---|---|
| US (1) | US7615547B2 (en) |
| EP (1) | EP1275377B1 (en) |
| JP (1) | JP2004536118A (en) |
| KR (1) | KR100877628B1 (en) |
| AT (1) | ATE243028T1 (en) |
| AU (1) | AU2002328866B2 (en) |
| BR (1) | BR0211081A (en) |
| CA (1) | CA2452386C (en) |
| DE (1) | DE60100389T2 (en) |
| DK (1) | DK1275377T3 (en) |
| ES (1) | ES2199202T3 (en) |
| HR (1) | HRP20040010A2 (en) |
| IL (1) | IL159346A0 (en) |
| MX (1) | MXPA04000211A (en) |
| NO (1) | NO20040043L (en) |
| NZ (1) | NZ530473A (en) |
| PL (1) | PL204963B1 (en) |
| PT (1) | PT1275377E (en) |
| RU (1) | RU2288704C2 (en) |
| WO (1) | WO2003005989A2 (en) |
| ZA (1) | ZA200309680B (en) |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6579319B2 (en) | 2000-11-29 | 2003-06-17 | Medicinelodge, Inc. | Facet joint replacement |
| US20050080486A1 (en) | 2000-11-29 | 2005-04-14 | Fallin T. Wade | Facet joint replacement |
| US7588590B2 (en) | 2003-12-10 | 2009-09-15 | Facet Solutions, Inc | Spinal facet implant with spherical implant apposition surface and bone bed and methods of use |
| PT1795183E (en) * | 2005-12-09 | 2009-08-21 | Teva Pharma | Aqueous dispersions and solutions of difficult to dissolve compounds and methods of their preparation |
| CN101600419B (en) * | 2006-12-22 | 2012-05-09 | 株式会社柳韩洋行 | Revaprazan-containing solid dispersion and process for the preparation thereof |
| EP3702442A1 (en) | 2011-12-22 | 2020-09-02 | Life Technologies Corporation | Cell culture media and methods |
| US10328087B2 (en) | 2015-07-23 | 2019-06-25 | Therapeuticsmd, Inc. | Formulations for solubilizing hormones |
| WO2017173071A1 (en) | 2016-04-01 | 2017-10-05 | Therapeuticsmd, Inc. | Steroid hormone pharmaceutical composition |
| WO2017173044A1 (en) | 2016-04-01 | 2017-10-05 | Therapeuticsmd Inc. | Steroid hormone compositions in medium chain oils |
| EP3641726A1 (en) * | 2017-06-23 | 2020-04-29 | MedCan Pharma A/S | Cannabinoid pouch |
| CN108309933A (en) * | 2018-03-19 | 2018-07-24 | 青岛国海生物制药有限公司 | A kind of oral megestrol acetate nanosuspension and preparation method thereof |
Family Cites Families (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3610037A1 (en) * | 1986-03-21 | 1987-09-24 | Schering Ag | NIFEDIPINE COMBINATION PRODUCT |
| JPH0449232A (en) | 1990-06-15 | 1992-02-18 | Fujisawa Pharmaceut Co Ltd | Composition of suspension or suspension and preparation therefrom |
| US5338732A (en) | 1991-06-18 | 1994-08-16 | Bristol-Myers Squibb Company | Megestrol acetate formulation |
| US5395627A (en) * | 1992-09-04 | 1995-03-07 | Akzo N.V. | Pharmaceutical granulate |
| FR2702968B1 (en) | 1993-03-23 | 1995-06-23 | Lafon Labor | Process for the preparation of particles containing an active ingredient by extrusion and lyophilization. |
| EP1475091A1 (en) | 1993-10-01 | 2004-11-10 | Roche Palo Alto LLC | Mycophenolate mofetil - high dose oral suspensions |
| US5976570A (en) * | 1993-12-21 | 1999-11-02 | Applied Analytical Industries, Inc. | Method for preparing low dose pharmaceutical products |
| FR2730163B1 (en) | 1995-02-03 | 1997-04-04 | Jouveinal Lab | NOVEL PHARMACEUTICAL COMPOSITION CONTAINING TRIMEBUTINE AND PROCESS FOR THE PREPARATION THEREOF |
| EP0914822A4 (en) | 1996-03-14 | 2002-08-07 | Bayer Ag | Rapid-release microdispersible ecadotril preparation |
| US5985309A (en) * | 1996-05-24 | 1999-11-16 | Massachusetts Institute Of Technology | Preparation of particles for inhalation |
| DE19637082A1 (en) * | 1996-09-12 | 1998-03-19 | Boehringer Mannheim Gmbh | Rapidly disintegrating pellets |
| TW486370B (en) * | 1996-12-25 | 2002-05-11 | Yamanouchi Pharma Co Ltd | Rapidly disintegrable pharmaceutical composition |
| US6028065A (en) * | 1998-04-20 | 2000-02-22 | Pharmaceutical Resources, Inc. | Flocculated suspension of megestrol acetate |
| ID29270A (en) | 1998-11-20 | 2001-08-16 | Rtp Pharma Inc | MICRO PARTICLES THAT ARE STABILIZED BY PHOSPHOLIPIDS THAT CAN SPREAD |
| US6316029B1 (en) * | 2000-05-18 | 2001-11-13 | Flak Pharma International, Ltd. | Rapidly disintegrating solid oral dosage form |
-
2001
- 2001-07-11 DE DE60100389T patent/DE60100389T2/en not_active Expired - Lifetime
- 2001-07-11 EP EP01202657A patent/EP1275377B1/en not_active Expired - Lifetime
- 2001-07-11 AT AT01202657T patent/ATE243028T1/en active
- 2001-07-11 ES ES01202657T patent/ES2199202T3/en not_active Expired - Lifetime
- 2001-07-11 DK DK01202657T patent/DK1275377T3/en active
- 2001-07-11 PT PT01202657T patent/PT1275377E/en unknown
-
2002
- 2002-07-09 NZ NZ530473A patent/NZ530473A/en not_active IP Right Cessation
- 2002-07-09 ZA ZA200309680A patent/ZA200309680B/en unknown
- 2002-07-09 AU AU2002328866A patent/AU2002328866B2/en not_active Ceased
- 2002-07-09 IL IL15934602A patent/IL159346A0/en not_active IP Right Cessation
- 2002-07-09 BR BR0211081-4A patent/BR0211081A/en not_active Application Discontinuation
- 2002-07-09 KR KR1020047000280A patent/KR100877628B1/en not_active IP Right Cessation
- 2002-07-09 WO PCT/EP2002/007636 patent/WO2003005989A2/en active IP Right Grant
- 2002-07-09 US US10/258,004 patent/US7615547B2/en not_active Expired - Fee Related
- 2002-07-09 MX MXPA04000211A patent/MXPA04000211A/en active IP Right Grant
- 2002-07-09 CA CA2452386A patent/CA2452386C/en not_active Expired - Fee Related
- 2002-07-09 PL PL369294A patent/PL204963B1/en not_active IP Right Cessation
- 2002-07-09 JP JP2003511797A patent/JP2004536118A/en active Pending
- 2002-07-09 RU RU2004103853/15A patent/RU2288704C2/en not_active IP Right Cessation
-
2004
- 2004-01-06 NO NO20040043A patent/NO20040043L/en unknown
- 2004-01-07 HR HR20040010A patent/HRP20040010A2/en not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| AU2002328866B2 (en) | 2007-02-15 |
| DE60100389T2 (en) | 2004-05-19 |
| RU2004103853A (en) | 2005-03-27 |
| BR0211081A (en) | 2004-12-14 |
| HRP20040010A2 (en) | 2004-06-30 |
| PL204963B1 (en) | 2010-02-26 |
| KR100877628B1 (en) | 2009-01-07 |
| DE60100389D1 (en) | 2003-07-24 |
| EP1275377A1 (en) | 2003-01-15 |
| NO20040043L (en) | 2004-01-06 |
| CA2452386C (en) | 2011-01-18 |
| RU2288704C2 (en) | 2006-12-10 |
| ES2199202T3 (en) | 2004-02-16 |
| JP2004536118A (en) | 2004-12-02 |
| KR20040018440A (en) | 2004-03-03 |
| PL369294A1 (en) | 2005-04-18 |
| WO2003005989A3 (en) | 2003-05-01 |
| MXPA04000211A (en) | 2005-03-07 |
| US7615547B2 (en) | 2009-11-10 |
| HRP20040010B1 (en) | 2007-01-31 |
| US20040009232A1 (en) | 2004-01-15 |
| DK1275377T3 (en) | 2003-10-06 |
| EP1275377B1 (en) | 2003-06-18 |
| WO2003005989A2 (en) | 2003-01-23 |
| PT1275377E (en) | 2003-11-28 |
| ZA200309680B (en) | 2004-12-22 |
| IL159346A0 (en) | 2004-06-01 |
| ATE243028T1 (en) | 2003-07-15 |
| NZ530473A (en) | 2006-02-24 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKLA | Lapsed |
Effective date: 20130709 |