WO1999009066B1 - Preparation of pregelatinized high amylose starch and debranched starch useful as an excipient for controlled release of active agents - Google Patents
Preparation of pregelatinized high amylose starch and debranched starch useful as an excipient for controlled release of active agentsInfo
- Publication number
- WO1999009066B1 WO1999009066B1 PCT/CA1998/000750 CA9800750W WO9909066B1 WO 1999009066 B1 WO1999009066 B1 WO 1999009066B1 CA 9800750 W CA9800750 W CA 9800750W WO 9909066 B1 WO9909066 B1 WO 9909066B1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- starch
- weight
- gelatinized
- excipient
- amylose
- Prior art date
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
- A61K9/20—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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
-
- 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
- A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
- C08B30/00—Preparation of starch, degraded or non-chemically modified starch, amylose, or amylopectin
- C08B30/12—Degraded, destructured or non-chemically modified starch, e.g. mechanically, enzymatically or by irradiation; Bleaching of starch
- C08B30/14—Cold water dispersible or pregelatinised starch
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
- C08B30/00—Preparation of starch, degraded or non-chemically modified starch, amylose, or amylopectin
- C08B30/20—Amylose or amylopectin
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Materials Engineering (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Polymers & Plastics (AREA)
- Organic Chemistry (AREA)
- Crystallography & Structural Chemistry (AREA)
- Medicinal Preparation (AREA)
Abstract
A process is disclosed for the manufacture of an excipient useful for the controlled release of an active agent. In this process, a starting material consisting of starch or high amylose starch is subjected to a gelatinization in an aqueous medium. When the starting material consists of starch having an amylose content of less than 50 % by weight, the gelatinized material is subjected to an enzymatic debranching treatment so as to obtain a gelatinized debranched starch having a short amylose chain content of at least 50 % by weight. When the starting material consists of starch having an amylose content of at least 50 % by weight or of a high amylose starch having an amylose content up to 80 % by weight, the gelatinized material is optionally subjected to an enzymatic debranching treatment so as to obtain a gelatinized debranched starch having a short amylose chain content of 20 % to 50 % by weight. The so obtained gelatinized and optionally debranched starch is further subjected to a thermal dehydration in order to obtain the requested excipient in form of a powder. Also disclosed is a dosage administration form for the sustained release of one or more active agents in the form of a powder. This form which is preferably a tablet, comprises the active agent(s) in admixture with the above excipient in such an amount as to achieve the requested sustained release.
Claims
1. A process for the manufacture of an excipient useful for the controlled release of an active agent, comprising the steps of: a) providing a starting material selected from the group consisting of starch and high amylose starch; b) subjecting the starting material to a gelatinization in an aqueous medium: c) when the starting material consists of starch having an amylose content of less than 50% by weight, subjecting said gelatinized material to an enzymatic debranching treatment so as to obtain a gelatinized debranched starch having a short amylose chain content of at least 50% by weight; and when the starting material consists of starch having an amylose content of at least 50% by weight or of a high amylose starch having an amylose content up to 80% by weight, optionally subjecting said gelatinized material to an enzymatic debranching treatment so as to obtain a gelatinized debranched starch having a short amylose chain content of 20% to 50% by weight, and d) drying the aqueous gelatinized and optionally debranched starch obtained in step c) in order to obtain the requested excipient in form of a powder, characterized in that: in step c), the enzymatic debranching treatment is carried out using a debranching enzyme capable of hydrolyzing the amylopectin molecules, exclusively; in step d), the drying is carried out by subjecting the aqueous gelatinized and optionally debranched starch to a thermal dehydration; and in the case where the aqueous gelatinized and optionally debranched starch obtained in step c) has been cooled and kept at a temperature in the range of 1 to 20°C for a given period of time, said aqueous gelatinized and optionally debranched starch is thermally treated at a temperature higher than 100°C prior to being subjected to the thermal dehydration.
2. The process of claim 1, wherein: in step b), the gelatinization consists of a thermo-mechanical treatment of an aqueous dispersion of the starting material.
3. The process of claim 2, wherein the aqueous dispersion contains from 1 to 20%) by weight of the starting material and the thermo-mechanical treatment of this aqueous dispersion is carried out in a scraped-surface heat exchanger at a temperature ranging from 1 10 to 160°C for 5 to 60 minutes.
4. The process of any one of claims 1 to 3, wherein: in step c), the enzymatic debranching treatment is carried out with pullulanase at a pH in the range of 3.5 to 6 and a temperature in the range of 35 to 65°C for 1 to 24 hours.
5. The process of any one of claims 1 to 4, wherein: in step d), the thermal dehydration is achieved by spray-drying of the aqueous gelatinized and optionally debranched material in the form of a solution that contains from 0.5 to 15% by weight of said material and is at a temperature of 20 to 90°C.
6. The process of claim 5, wherein the spray-drying is carried out with a spray-nozzle or rotating disc having an inlet temperature of 175 to 350°C and an outlet temperature of 60 to 135°C.
7. The process of claim 6, wherein the solution contains from 4 to 12%) by weight of the aqueous gelatinized and optionally debranched material and is at a temperature of 40 to 70°C.
8. The process of any one of claims 1 to 7, comprising the additional steps of: e) subjecting the powder obtained in step d) to a granulation.
9. The process of claim 8, wherein, in step e), the granulation is a wet granulation carried out in a fluid bed or high shear granulator.
10. The process of claim 8, wherein, in step e). the granulation is a dry granulation carried out in a roller compaction apparatus.
11. The process of any one of claims 1 to 10, wherein: in step a), use is made of a high amylose starch containing at least 50%) by weight of amylose as said starting material.
12. The process of claim 11. wherein said high amylose starch contains 70%> by weight of amylose.
13. The process of any one of claims 1 to 10, wherein: in step a), use is made of a common or waxy starch as said starting material.
14. The process of claim 13, wherein said common or waxy starch is cross-linked or substituted.
15. An excipient useful for the controlled release of an active agent, said excipient being in the form of a powder and being obtained by the process of any one of claims 1 to 14.
16. A dosage administration form for the sustained release of at least one active agent in the form of a powder, said form comprising said at least one active agent in admixture with an excipient as claimed in claim 15, said excipient being present in such an amount as to achieve the requested sustained release.
17. The dosage form of claim 16, containing at least 20%> by weight of said excipient.
18. The dosage form of claim 16, containing at least 60% by weight of said excipient.
19. The dosage form of claim 16. containing at least 94% by weight of said excipient.
20. The dosage form of claim 17 or 18, further containing up to 40% by weight a polymer that becomes viscous in the presence of water and thus may fill cracks formed in the form during its dissolution.
21. The dosage form of claim 20. wherein said polymer is selected from the group consisting of Carbopol® and Methocel®.
22. The dosage form of claim 21. wherein said polymer is Carbopol® and is present in an amount of about 5%> by weight.
23. The dosage form of claim 21. wherein said polymer is Methocel® and is present in an amount of about 10% by weight.
24. The dosage form of any one of claims 16 to 23. which is in the form of a tablet for oral administration.
35
STATEMENT UNDER ARTICLE 1 9
The original set of 25 claims has been deleted and replaced by a new set of 24 claims.
New claim 1 is cast into two parts in order to put emphasis on the characterizing features of the invention. Support for this new claim can be found in original claims 1 and 8 and on page 9, lines 1 9 to 26 and page 1 0, lines 20 to 25 of the original description.
New claims 2 and 3 are copies of original claims 2 and 3.
New claim 4 substantially corresponds to original claim 4, except that the reference made therein to use of starch as starting material has been deleted.
New claim 5 substantially corresponds to original claim 5, except that the word — aqueous- has been added before the word "gelatinized" and the word « eventually » has been replaced by the word -optionally- at line 3 thereof.
New claim 6 is a copy of original claim 6.
New claim 7 substantially corresponds to original claim 7, except that the word -- aqueous- has been added before the word "gelatin/zed" and the word « eventually » has been replaced by the word -optionally- at line 2 thereof.
New claims 8 to 24 are substantially correspond to former claims 9 to 25, respectively.
It is worth noting that the statement of the invention on page 8 of the description presently on file should be amended to conform to the invention as now reflected in new claim 1 .
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AU87241/98A AU8724198A (en) | 1997-08-14 | 1998-08-05 | Preparation of pregelatinized high amylose starch and debranched starch useful as an excipient for controlled release of active agents |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA2,211,778 | 1997-08-14 | ||
| CA 2211778 CA2211778A1 (en) | 1997-08-14 | 1997-08-14 | Preparation of pregelatinized high amylose starch and debranched starch useful as an excipient for controlled release of active agents |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| WO1999009066A1 WO1999009066A1 (en) | 1999-02-25 |
| WO1999009066B1 true WO1999009066B1 (en) | 1999-04-08 |
Family
ID=4161135
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/CA1998/000750 WO1999009066A1 (en) | 1997-08-14 | 1998-08-05 | Preparation of pregelatinized high amylose starch and debranched starch useful as an excipient for controlled release of active agents |
Country Status (3)
| Country | Link |
|---|---|
| AU (1) | AU8724198A (en) |
| CA (1) | CA2211778A1 (en) |
| WO (1) | WO1999009066A1 (en) |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2822471B1 (en) * | 2001-03-26 | 2003-06-13 | Roquette Freres | METHOD OF COOKING / DRYING AMYLOSE-RICH STARCHES |
| US6929817B2 (en) | 2002-05-14 | 2005-08-16 | National Starch & Chemical Investment Holding Corporation | Slowly digestible starch product |
| US7081261B2 (en) | 2002-05-14 | 2006-07-25 | National Starch And Chemical Investment Holding Corporation | Resistant starch prepared by isoamylase debranching of low amylose starch |
| US20030215499A1 (en) * | 2002-05-14 | 2003-11-20 | Yong-Cheng Shi | Use of completely linear short chain alpha-glucans as a pharmaceutical excipient |
| AR040682A1 (en) * | 2002-07-25 | 2005-04-13 | Pharmacia Corp | DOSAGE FORM ONCE A DAY OF PRAMIPEXOL |
| US20050226926A1 (en) * | 2002-07-25 | 2005-10-13 | Pfizer Inc | Sustained-release tablet composition of pramipexole |
| US20050079217A1 (en) * | 2002-07-25 | 2005-04-14 | Ganorkar Loksidh D. | Sustained-release tablet composition comprising a dopamine receptor agonist |
| MY136318A (en) * | 2002-07-25 | 2008-09-30 | Pharmacia Corp | Sustained-release tablet composition |
| EP1645568A4 (en) * | 2003-07-11 | 2007-06-27 | Asahi Kasei Chemicals Corp | Functional starch powder |
| CN101849921A (en) | 2004-08-13 | 2010-10-06 | 贝林格尔·英格海姆国际有限公司 | The prolongation release tablet that comprises pramipexole or its officinal salt |
| US8318230B2 (en) | 2005-05-02 | 2012-11-27 | Henkel Ag & Co. Kgaa | Use of debranched starch in extrusion-spheronization pharmaceutical pellets |
| CN101304764B (en) | 2005-11-11 | 2012-12-05 | 旭化成化学株式会社 | Solid formulation to control-release |
| CN102202648B (en) * | 2008-10-23 | 2014-07-23 | 汉高公司 | Pharmaceutical pellets comprising modified starch |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5468286A (en) * | 1989-10-25 | 1995-11-21 | National Starch And Chemical Investment Holding Corporation | Enzymatically debranched starches as tablet excipients |
| CA2032385A1 (en) * | 1990-12-17 | 1992-06-18 | Chung Wai-Chiu | Enzymatically debranched starches as tablet excipients |
| NL9201195A (en) * | 1992-07-03 | 1994-02-01 | Tno | PREPARATION FOR THE REGULATED DELIVERY OF AN ACTIVE SUBSTANCE AND METHOD FOR PREPARING SUCH A PREPARATION. |
| NL9401572A (en) * | 1994-09-27 | 1996-05-01 | Avebe Coop Verkoop Prod | Starch products such as tableting excipient, method of preparation thereof, and method of making tablets. |
| NL1003747C2 (en) * | 1996-08-06 | 1998-02-12 | Avebe Coop Verkoop Prod | Amylose products as matrix former for programmed delivery systems, method for preparing these amylose products as well as method for making programmed delivery systems. |
-
1997
- 1997-08-14 CA CA 2211778 patent/CA2211778A1/en not_active Abandoned
-
1998
- 1998-08-05 WO PCT/CA1998/000750 patent/WO1999009066A1/en active Application Filing
- 1998-08-05 AU AU87241/98A patent/AU8724198A/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| WO1999009066A1 (en) | 1999-02-25 |
| CA2211778A1 (en) | 1999-02-14 |
| AU8724198A (en) | 1999-03-08 |
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