WO1986006627A1 - Sustained release theophylline compositions and processes - Google Patents
Sustained release theophylline compositions and processes Download PDFInfo
- Publication number
- WO1986006627A1 WO1986006627A1 PCT/US1986/001025 US8601025W WO8606627A1 WO 1986006627 A1 WO1986006627 A1 WO 1986006627A1 US 8601025 W US8601025 W US 8601025W WO 8606627 A1 WO8606627 A1 WO 8606627A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- theophylline
- weight
- sustained
- guar gum
- release
- Prior art date
Links
- ZFXYFBGIUFBOJW-UHFFFAOYSA-N theophylline Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC=N2 ZFXYFBGIUFBOJW-UHFFFAOYSA-N 0.000 title claims abstract description 126
- 229960000278 theophylline Drugs 0.000 title claims abstract description 62
- 239000000203 mixture Substances 0.000 title claims abstract description 53
- 238000013268 sustained release Methods 0.000 title claims abstract description 28
- 239000012730 sustained-release form Substances 0.000 title claims abstract description 28
- 238000000034 method Methods 0.000 title claims abstract description 12
- 229920002907 Guar gum Polymers 0.000 claims abstract description 26
- 239000000665 guar gum Substances 0.000 claims abstract description 26
- 229960002154 guar gum Drugs 0.000 claims abstract description 26
- 235000010417 guar gum Nutrition 0.000 claims abstract description 25
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 14
- 238000001035 drying Methods 0.000 claims description 9
- 239000002245 particle Substances 0.000 claims description 7
- 239000007788 liquid Substances 0.000 claims description 4
- 239000007939 sustained release tablet Substances 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 239000011363 dried mixture Substances 0.000 claims description 2
- 241000124008 Mammalia Species 0.000 claims 2
- 230000007883 bronchodilation Effects 0.000 claims 1
- 230000001939 inductive effect Effects 0.000 claims 1
- 238000012216 screening Methods 0.000 claims 1
- 230000000144 pharmacologic effect Effects 0.000 abstract description 2
- 239000003826 tablet Substances 0.000 description 11
- 239000008187 granular material Substances 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 238000005469 granulation Methods 0.000 description 3
- 230000003179 granulation Effects 0.000 description 3
- 235000019359 magnesium stearate Nutrition 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- 229920001155 polypropylene Polymers 0.000 description 2
- 238000005507 spraying Methods 0.000 description 2
- 238000005550 wet granulation Methods 0.000 description 2
- 241000219748 Cyamopsis Species 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- 241000497429 Obus Species 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 238000007906 compression Methods 0.000 description 1
- 230000006835 compression Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 229940111685 dibasic potassium phosphate Drugs 0.000 description 1
- ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000007922 dissolution test Methods 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- 229960004667 ethyl cellulose Drugs 0.000 description 1
- 210000005095 gastrointestinal system Anatomy 0.000 description 1
- 230000036571 hydration Effects 0.000 description 1
- 238000006703 hydration reaction Methods 0.000 description 1
- 239000008172 hydrogenated vegetable oil Substances 0.000 description 1
- -1 hydroxypropyl ethyl Chemical group 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 229940068968 polysorbate 80 Drugs 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- XOOUIPVCVHRTMJ-UHFFFAOYSA-L zinc stearate Chemical compound [Zn+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O XOOUIPVCVHRTMJ-UHFFFAOYSA-L 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
- A61K31/52—Purines, e.g. adenine
-
- 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
Definitions
- This invention relates to theophylline sustained-release compositions, processes for preparing str ⁇ h compositions and pharmacological methods for using such compositions.
- theophylline sustained-release tablets having a high concentration of theophylline (about 85% or greater by weight of theophylline) and a sustained-release profile of. theophylline for between 6 and 24 hours.
- a prescribed dosage of theophylline for a prescribed dosage of theophylline,. fewer tablets overall and per 24 hour period have to be consumed and less sustained-release agent is required per tablet.
- Another advantage is the tablet size can be smaller.
- U. S. Patent No. 4,264,573 discloses sustained-release compositions which comprise 30 to 90? by weight of a medicament and one or more excipients such as a binder.
- the medicament may be theophylline.
- a wet granulation process is disclosed for preparing these sustained-release products.
- the present invention provides a novel theophylline sustained-release composition
- a novel theophylline sustained-release composition comprising about 85-98% by weight of theophylline and about 2-15 by weight of guar gum, the composition being prepared by granulating a mixture of the theophylline (in particulate form) and the guar gum in the presence of water as a granulating liquid, and substantially drying the mixture.
- This composition may, for example, then be manufactured into a sustained-release tablet.
- the theophylline sustained-release compositions of the present invention desirably comprise a high percentage of theophylline and provide a desirable profile of susta ned-release of theophylline when incorporated in tablet form.
- the sustained-release rate of theophylline from such tablets is not signif cantly affected by the acidity or alkalinity of solutions which simulate the different acidity or alkalinity expected within the normal range of pH in a human gastrointestinal system.
- the rate of release and period of release of theophylline can be controlled in the instant compositions by varying the proportion of theophylline to guar gum.
- the theophylline sustained-release compositions may be manufactured using conventional equipment and can be manufactured into tablets using conventional tabletting equipment.
- the theophylline sustained-release compositions of the present invention comprise about 85-98% by weight, preferably about 90-98% by weight, and most preferably about 95% by weight of theophylline.
- the guar gum which acts as the sustained-release agent it is present in the theophylline sustained-release compositions of the invention in an amount of about 2-15% by wei ght, . preferably about 2-10% by weight and most preferably about 5% by weight.
- guar gum as used in the instant specifications and claims is meant that material so specified in the USP XXI NF XVI. Guar gum ' is the ground endosperm of the plant Cyamopsis tetragonul obus (Linn ⁇ ).
- the theophylline sustained-release compositions of the present invention are prepared by granulating a mixture of theophylline (in particulate form), guar gum and water as a granulating liquid, and thereafter substantially drying the mixture.
- particulate form is meant that the majority of the theophylline particles are in the range of about 20 to 500 micrometers in diameter.
- substantially drying is meant that the level of water in the dried mixture is less than about 2% (weight/weight).
- the water content is between 0% and 0.5% (weig t/weight).
- a conventional granulating device may be used.
- the preferred drying step involves the use of a fluid bed -4- dryer .
- a preferred process of the present invention comprises the following steps.
- Theophylline is prescreened through an appropriate mesh screen to provide particles of the desired size.
- Such theophylline is then granulated with guar gum in the presence of water as the granulating liqu . id, the water being added by spraying.
- the theophyl 1 i ne-guar gum mixture is screened either in the wet state or dry state to provide particles of tftfe descri bed size. If the mixture is screened in the wet-state, it is thereafter dried.
- compositions of the invention may be prepared using and the processes of the invention may involve a simultaneous granulation and drying procedures.
- the desired sustained-release characteristics of the instant compositions result from the formation of a film of guar gum around the theophylline particles. Formation of such a film is believed to result from hydration of the guar gum and the coating of theophylline particles with hydrated guar gum during the wet granulation process.
- acceptable pharmaceutical compression lubricants such as magnesium stearate, stearic acid, zinc stearate, the hydrogenated vegetable oil which is available under the trade s_ designation Sterotex from Capital City Products, USA, or other like lubricants may desirably be employed.
- Theophylline compositions containing about 2%, about 4.8%, about 9.1% and about 16.6% of guar gum by weight were prepared as follows. 1kg of theophylline was screened through a 20 mesh screen and placed in a planetary mixing device. Powdered guar gum (Supercol U from Polypro International Inc. (USA)), in one of the amounts indicated in Table 1, was added to the theophylline and the combination blended to provide a uniform mixture. Water, in the amount specified in Table 1 for the amount of guar gum used, was then added by spraying at a rate of 1.5 liters/hour into the mixture while mixing to maintain a homogeneous granulation.
- Powdered guar gum Supercol U from Polypro International Inc. (USA)
- Water in the amount specified in Table 1 for the amount of guar gum used, was then added by spraying at a rate of 1.5 liters/hour into the mixture while mixing to maintain a homogeneous granulation.
- the wet granules so formed were then dried at 60 for 24 hours to a moisture content of 0.4% and were subsequently dry-screened through a 16 mesh screen. 1kg of the dry-screened mixture was blended with lg of magnesium stearate and the blended mixture was converted into
- the dry granulate was screened through a 16 mesh screen. Tabletting was accomplished as follows. One-tenth kg ' -of dried and screened granulate from above was hand mixed with 0.001 kg of magnesium stearate in a plastic bag. The resulting mixture was blended with a further 0.9 kg of dried and screened theophylline granulate in a cube blender for 15 minutes. Tablets containing 250 mg of theophylline were then manufactured using a single punch rotary machine using 3/8" biconcave punches.
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Sustained-release theophylline products comprising theophylline in an amount of about 85 to 98% by weight and guar gum in an amount of about 2 to 15% by weight. Processes for preparaing such compositions and pharmacological methods for using such compositions are also disclosed.
Description
'"SUSTAINED RELEASE THEOPHYLLINE COMPOSITIONS AND PROCESSES'
TECHNICAL FIELD
.This invention relates to theophylline sustained-release compositions, processes for preparing strøh compositions and pharmacological methods for using such compositions.
BACKGROUND OF THE INVENTION
There are applications for theophylline sustained-release tablets having a high concentration of theophylline (about 85% or greater by weight of theophylline) and a sustained-release profile of. theophylline for between 6 and 24 hours. For example, for a prescribed dosage of theophylline,. fewer tablets overall and per 24 hour period have to be consumed and less sustained-release agent is required per tablet. Another advantage is the tablet size can be smaller.
There are also applications for theophylline sustained-release tablets in which the rate of release of theophylline is substantially unaffected by the acidity or alkalinity of the releasing medium. Individuals have different internal acidity levels, in particular in the stomach, and this can cause variations in the sustained-release rate if it is pH dependent.
Substained-release theophylline products are known. For example, U. S. Patent No. 4,389,393 discloses sustained-release compositions which contain theophylline as the medicament and a high molecular weight hydroxypropyl ethyl cell ulose as the sustained-release agent. This patent generally discloses that the hydroxypropylmethylcell ulose may be present in an amount of
5 to about 30% weight.
Further, U. S. Patent No. 4,264,573 discloses sustained-release compositions which comprise 30 to 90? by weight of a medicament and one or more excipients such as a binder. The medicament may be theophylline. A wet granulation process is disclosed for preparing these sustained-release products.
BRIEF SUMMARY OF THE INVENTION
The present invention provides a novel theophylline sustained-release composition comprising about 85-98% by weight of theophylline and about 2-15 by weight of guar gum, the composition being prepared by granulating a mixture of the theophylline (in particulate form) and the guar gum in the presence of water as a granulating liquid, and substantially drying the mixture. This composition may, for example, then be manufactured into a sustained-release tablet.
The present invention also provides a process for preparing a theophylline sustained-release composition comprising the steps of a) granulating a mixture comprising about 85-98 parts by weight of theophylline (in particulate form) and about 2-15 parts by weight of guar gum in the presence of water as a granulating liquid, and b) substantially drying the mixture.
The theophylline sustained-release compositions of the present invention desirably comprise a high percentage of theophylline and provide a desirable profile of susta ned-release of theophylline when incorporated in tablet form. Further, desirably the sustained-release rate of theophylline from such tablets is not signif cantly affected by the acidity or alkalinity of solutions which simulate the different acidity or alkalinity expected within the normal range of pH in a human gastrointestinal
system. Other advantages are that the rate of release and period of release of theophylline can be controlled in the instant compositions by varying the proportion of theophylline to guar gum. Further, the theophylline sustained-release compositions may be manufactured using conventional equipment and can be manufactured into tablets using conventional tabletting equipment.
DETAILED DESCRIPTION OF THE INVENTION
The theophylline sustained-release compositions of the present invention comprise about 85-98% by weight, preferably about 90-98% by weight, and most preferably about 95% by weight of theophylline. As for the guar gum which acts as the sustained-release agent, it is present in the theophylline sustained-release compositions of the invention in an amount of about 2-15% by wei ght, . preferably about 2-10% by weight and most preferably about 5% by weight. By "guar gum" as used in the instant specifications and claims is meant that material so specified in the USP XXI NF XVI. Guar gum' is the ground endosperm of the plant Cyamopsis tetragonul obus (Linnέ).
The theophylline sustained-release compositions of the present invention are prepared by granulating a mixture of theophylline (in particulate form), guar gum and water as a granulating liquid, and thereafter substantially drying the mixture. By "particulate form" is meant that the majority of the theophylline particles are in the range of about 20 to 500 micrometers in diameter. By "substantially drying" is meant that the level of water in the dried mixture is less than about 2% (weight/weight). Preferably, the water content is between 0% and 0.5% (weig t/weight).
As for the processes of the present invention for preparing the theophylline sustained-release compositions, a conventional granulating device may be used. The preferred drying step involves the use of a fluid bed
-4- dryer .
A preferred process of the present invention comprises the following steps. Theophylline is prescreened through an appropriate mesh screen to provide particles of the desired size. Such theophylline is then granulated with guar gum in the presence of water as the granulating liqu.id, the water being added by spraying. Thereafter, the theophyl 1 i ne-guar gum mixture is screened either in the wet state or dry state to provide particles of tftfe descri bed size. If the mixture is screened in the wet-state, it is thereafter dried.
While, as noted above, theophylline and guar gum are first granulated in the presence of water and then dried, the compositions of the invention may be prepared using and the processes of the invention may involve a simultaneous granulation and drying procedures.
While not wishing to be bound to any particular theory, it is believed that the desired sustained-release characteristics of the instant compositions result from the formation of a film of guar gum around the theophylline particles. Formation of such a film is believed to result from hydration of the guar gum and the coating of theophylline particles with hydrated guar gum during the wet granulation process. In manufacturing tablets comprising the theophylline sustained-release compositions of the invention, acceptable pharmaceutical compression lubricants such as magnesium stearate, stearic acid, zinc stearate, the hydrogenated vegetable oil which is available under the trade s_ designation Sterotex from Capital City Products, USA, or other like lubricants may desirably be employed.
Preferred embodiments of this invention are described by way of Example.
EXAMPLE 1
Theophylline compositions containing about 2%, about 4.8%, about 9.1% and about 16.6% of guar gum by weight were prepared as follows. 1kg of theophylline was screened through a 20 mesh screen and placed in a planetary mixing device. Powdered guar gum (Supercol U from Polypro International Inc. (USA)), in one of the amounts indicated in Table 1, was added to the theophylline and the combination blended to provide a uniform mixture. Water, in the amount specified in Table 1 for the amount of guar gum used, was then added by spraying at a rate of 1.5 liters/hour into the mixture while mixing to maintain a homogeneous granulation.
TABLE 1
Guar gum (g) Volume of Water (ml )
0 170
20 460
50 550
100 700 200 900
The wet granules so formed were then dried at 60 for 24 hours to a moisture content of 0.4% and were subsequently dry-screened through a 16 mesh screen. 1kg of the dry-screened mixture was blended with lg of magnesium stearate and the blended mixture was converted into
3/8-inch diameter biconvex tablets using a single punch rotary tabletting machine.
For each of the above tabletted compositions, the release of theophylline versus time was determined by dissolution tests conducted as follows: A USP XXI dissolution apparatus (paddle) was employed. The medium used was 875 ml of 0.1M hydrochloric acid, containing 0.05% by weight of polysorbate 80. Forty-five minutes into the procedure there was added to the medium dibasic potassium
phosphate as a solid in an amount of 6. lg. At 90 minutes, • the pH was titrated to a pH of 7.5 with a solution of sodium hydroxide. Mean values of theophylline released (expressed as a percentage of theophylline in a tablet) 'for 6 tablets of each of the above-prepared compositions are included in Table 2.
TABLE 2
% guar gum Theophyl! ine Theophyl line released after released after 6 hours 12 hours
02 . 100% 100%
0 . 2% 75.8% 98.7%
4 . 8% 42.3% 67.2%
9 . 1 % 32.1% 51.5%
1 166..6 6%% 28.3% 43.8%
E X AMP L E 2 >
Four kg of anhydrous theophylline was screened through a 20 mesh screen. The sieved theophylline was then blended o with 0.20 kg of Supercol U (guar gum; available from
Polypro International Inc.) in a "Diosna V25" high speed mi xer/granulator (available from Dierks and Sohne, West Germany) for two minutes at low speed. While mixing was continued, 1870 ml of water was added to the mixture at a rate of 500 ml per minute as a fine spray. Mixing was continued for an additional 2 minutes at low speed. Granulation was completed by mixing for 30 seconds at high speed with the chopping blade on. After waiting 30 minutes from the first addition of water, the wet granulate was dried in a fluid bed dryer with an inlet temperature of 60°C. and a final outlet temperature of 35°C. (loss on drying of granules of 0.4%). The dry granulate was screened through a 16 mesh screen.
Tabletting was accomplished as follows. One-tenth kg '-of dried and screened granulate from above was hand mixed with 0.001 kg of magnesium stearate in a plastic bag. The resulting mixture was blended with a further 0.9 kg of dried and screened theophylline granulate in a cube blender for 15 minutes. Tablets containing 250 mg of theophylline were then manufactured using a single punch rotary machine using 3/8" biconcave punches.
Claims
1. A theophylline sustained-release composition comprising about 85-98% by weight of theophylline and about 2-15% by weight of guar gum, said composition being prepared by granulating a mixture of said theophylline in particulate form, said guar gum and water as a granulating liquid, and substantially drying said mixture.
2. A theophylline sustained-release composition according to Claim 1, wherein said composition comprises about 90-98% by weight of theophylline and about 2-10% by weight of guar gum.
3. A theophylline sustained-release composition according to Claim 1, wherein said composition comprises about 95% by weight of theophylline and about 5% by weight of guar gum.
4. A theophylline sustained-release tablet comprising theophylline sustained-release composition of Claim 1.
5. A process for preparing a theophylline sustained-release composition comprising the steps of a) granulating a mixture comprising about 85-98 parts by weight of theophylline in particulate form and about 2-15 parts by weight of guar gum in the presence of water as a granulating liqui , and b) substantially drying said mixture.
6. A process according to Claim 5, further comprising the step of screening the dried mixture from step b) to provide particles of the desired particle size.
7. A method for inducing bronchodi lation in a mammal comprising administering orally to said mammal a composition according to Claim 1 in an amount sufficient to induce bronchodi lati on.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AUPH0577 | 1985-05-15 | ||
| AUPH057785 | 1985-05-15 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO1986006627A1 true WO1986006627A1 (en) | 1986-11-20 |
Family
ID=3771108
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/US1986/001025 WO1986006627A1 (en) | 1985-05-15 | 1986-05-15 | Sustained release theophylline compositions and processes |
Country Status (2)
| Country | Link |
|---|---|
| EP (1) | EP0222883A1 (en) |
| WO (1) | WO1986006627A1 (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0270305A3 (en) * | 1986-12-02 | 1990-10-10 | Euroceltique Sa | Spheroids |
| GB2279871A (en) * | 1993-06-23 | 1995-01-18 | Jevco Ltd | Active agent delivery systems |
| US5656294A (en) * | 1995-06-07 | 1997-08-12 | Cibus Pharmaceutical, Inc. | Colonic delivery of drugs |
| EP0804169A4 (en) * | 1994-12-01 | 1998-08-19 | Cibus Pharmaceutical Inc | NSAID ADMINISTRATION USING A POWDERED HYDROCOLLOID GUM MACHINABLE FROM HIGHER PLANTS |
| US5811388A (en) * | 1995-06-07 | 1998-09-22 | Cibus Pharmaceutical, Inc. | Delivery of drugs to the lower GI tract |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3590117A (en) * | 1969-03-24 | 1971-06-29 | Richardson Merrell Inc | Long-lasting troche containing guar gum |
| FR2310764A1 (en) * | 1975-05-10 | 1976-12-10 | Hoechst Ag | ORAL-ADMINISTERED SOLID DRUG FORMS OF WATER-SOLUBLE XANTHINE DERIVATIVES |
-
1986
- 1986-05-15 WO PCT/US1986/001025 patent/WO1986006627A1/en unknown
- 1986-05-15 EP EP19860903796 patent/EP0222883A1/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3590117A (en) * | 1969-03-24 | 1971-06-29 | Richardson Merrell Inc | Long-lasting troche containing guar gum |
| FR2310764A1 (en) * | 1975-05-10 | 1976-12-10 | Hoechst Ag | ORAL-ADMINISTERED SOLID DRUG FORMS OF WATER-SOLUBLE XANTHINE DERIVATIVES |
Non-Patent Citations (1)
| Title |
|---|
| Chemical and Pharmaceutical Bulletin, Vol. 32, No. 2, February 1984 (Tokyo, JP) M. NAKANO et al.: "Examination of Natural Gums as Matrices for Sustained Release of Theophylline", pages 782-785, see the whole article * |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0270305A3 (en) * | 1986-12-02 | 1990-10-10 | Euroceltique Sa | Spheroids |
| GB2279871A (en) * | 1993-06-23 | 1995-01-18 | Jevco Ltd | Active agent delivery systems |
| GB2279871B (en) * | 1993-06-23 | 1997-05-07 | Jevco Ltd | Drug retention systems for use in aquaculture |
| EP0804169A4 (en) * | 1994-12-01 | 1998-08-19 | Cibus Pharmaceutical Inc | NSAID ADMINISTRATION USING A POWDERED HYDROCOLLOID GUM MACHINABLE FROM HIGHER PLANTS |
| US5656294A (en) * | 1995-06-07 | 1997-08-12 | Cibus Pharmaceutical, Inc. | Colonic delivery of drugs |
| US5811388A (en) * | 1995-06-07 | 1998-09-22 | Cibus Pharmaceutical, Inc. | Delivery of drugs to the lower GI tract |
Also Published As
| Publication number | Publication date |
|---|---|
| EP0222883A1 (en) | 1987-05-27 |
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