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WO1986006627A1 - Procedes et compositons de theophylline a liberation entretenue - Google Patents

Procedes et compositons de theophylline a liberation entretenue Download PDF

Info

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
Application number
PCT/US1986/001025
Other languages
English (en)
Inventor
Phillip G. Osborn
Original Assignee
Riker Laboratories, Inc.
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Riker Laboratories, Inc. filed Critical Riker Laboratories, Inc.
Publication of WO1986006627A1 publication Critical patent/WO1986006627A1/fr

Links

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.

Landscapes

  • 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

Des produits de théophylline à libération entretenue comprennent entre 85 et 98% en poids environ de théophylline et entre 2 et 15% en poids environ de gomme guar. L'invention concerne également des procédés de préparation de ces compositions et des procédés pharmacologiques d'utilisation de ces compositions.
PCT/US1986/001025 1985-05-15 1986-05-15 Procedes et compositons de theophylline a liberation entretenue WO1986006627A1 (fr)

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 (fr) 1986-11-20

Family

ID=3771108

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1986/001025 WO1986006627A1 (fr) 1985-05-15 1986-05-15 Procedes et compositons de theophylline a liberation entretenue

Country Status (2)

Country Link
EP (1) EP0222883A1 (fr)
WO (1) WO1986006627A1 (fr)

Cited By (5)

* Cited by examiner, † Cited by third party
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 (fr) * 1994-12-01 1998-08-19 Cibus Pharmaceutical Inc Apport d'un anti-inflammatoire non steroidien au moyen d'une gomme hydrocolloidale en poudre pouvant etre obtenue a partir des plantes superieures
US5811388A (en) * 1995-06-07 1998-09-22 Cibus Pharmaceutical, Inc. Delivery of drugs to the lower GI tract

Citations (2)

* Cited by examiner, † Cited by third party
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 (fr) * 1975-05-10 1976-12-10 Hoechst Ag Formes medicamenteuses solides, administrees par voie orale, de derives de xanthine solubles dans l'eau

Patent Citations (2)

* Cited by examiner, † Cited by third party
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 (fr) * 1975-05-10 1976-12-10 Hoechst Ag Formes medicamenteuses solides, administrees par voie orale, de derives de xanthine solubles dans l'eau

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
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)

* Cited by examiner, † Cited by third party
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 (fr) * 1994-12-01 1998-08-19 Cibus Pharmaceutical Inc Apport d'un anti-inflammatoire non steroidien au moyen d'une gomme hydrocolloidale en poudre pouvant etre obtenue a partir des plantes superieures
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 (fr) 1987-05-27

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