WO1984000004A1 - Aspirine a liberation entretenue - Google Patents

Aspirine a liberation entretenue Download PDF

Info

Publication number
WO1984000004A1
WO1984000004A1 PCT/US1983/000928 US8300928W WO8400004A1 WO 1984000004 A1 WO1984000004 A1 WO 1984000004A1 US 8300928 W US8300928 W US 8300928W WO 8400004 A1 WO8400004 A1 WO 8400004A1
Authority
WO
WIPO (PCT)
Prior art keywords
aspirin
dosage form
sustained release
weight
period
Prior art date
Application number
PCT/US1983/000928
Other languages
English (en)
Inventor
Hsiao Charles
Original Assignee
Key Pharma
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 Key Pharma filed Critical Key Pharma
Priority to JP50239683A priority Critical patent/JPS59501067A/ja
Publication of WO1984000004A1 publication Critical patent/WO1984000004A1/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
    • A61K31/60—Salicylic acid; Derivatives thereof
    • 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
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5005—Wall or coating material
    • A61K9/5021—Organic macromolecular compounds
    • A61K9/5036—Polysaccharides, e.g. gums, alginate; Cyclodextrin
    • A61K9/5042—Cellulose; Cellulose derivatives, e.g. phthalate or acetate succinate esters of hydroxypropyl methylcellulose
    • A61K9/5047—Cellulose ethers containing no ester groups, e.g. hydroxypropyl methylcellulose

Definitions

  • a sustained release aspirin preparation which comprises a plurality of crystals which disperse in the gastrointestinal tract to avoid localized irritation, the coated crystals also providing a sustained release with the release of the aspirin over a period of at least about eight hours, thereby reducing the appli ⁇ cation of aspirin to a patient in need thereof.
  • read inistration of aspirin for headaches may not pose a major inconvenience, it is to be particularly noted that for an adult suffering from arthritis who may need an at least eight hour protection to avoid being wakened from the pain of such arthritis (or other chronic disease) during a normal period of overnight sleep, the provision of a sustained release form that provides an at least eight hour protection is highly desirable.
  • the sustained release aspirin prepa ⁇ ration of the present invention it is possible for the pain relief to last until the normal waking time of the patient, permitting an unbroken sleeping pattern throughout the night.
  • another important use of the coated crystals of the present invention is pediatric, to provide an *• overnight" dosage of aspirin for small children who often run high fevers and, without such an overnight dosage, would be awakened in the middle of the night.
  • the present invention provides a sustained release aspirin dosage form to permit the continuous delivery of aspirin into the gastrointestinal tract for a period of at least eight hours which comprises a plurality of polymerically coated aspirin crystals which each comprise an aspirin seed, the majority of aspirin seeds having a mesh size of from about 30 to about 60 mesh, each of said aspirin sees being individually coated with a polymeric mixture which comprises from about 1.5 to about 15 parts by weight ethylcellulose and about one part by weight hydroxypropylcellulose.
  • the dosage form may be, for example, a capsule, which in the case of an adult or older child may be taken whole and which dissolves in the stomach, there releasing the polymerically coated aspirin tablets.
  • the drug may be sprinkled onto food or mixed with a beverage and so taken, the polymeric coat ⁇ ing masking the unpleasant taste of the aspirin.
  • the dosage form may be, for example, a capsule that is easily opened without diffi ⁇ culty, to avoid spilling of the contents.
  • a preferred embodiment for a capsule to be used merely to store the drug, and not necessarily to be swallowed is disclosed in Keith, "Anti-Spilling Drug Capsule," United States patent application Serial No. 338,257, filed January 11, 1982, the entire specification of which is hereby incorporated by reference herein.
  • a sealed pouch preferably constructed of a poly ⁇ ester film (Mylar) may be used to house the polymeri ⁇ cally coated aspirin crystals.
  • the aspirin that is used as the "seed" for the present invention may be granulated or may be compounded with other conven ⁇ tional tableting ingredients, in accordance with a preferred aspect of the present invention it is contem ⁇ plated that pure aspirin crystals may be used.
  • the aspirin furthermore, should have a relatively uniform particle size distribution, which has been found to be important to achieving relative linearity of release over a prolonged period of time.
  • the aspirin "seeds” should be selected for a particle size which ranges from about 30 to about 60 mesh. It is contemplated that while minor amounts of the aspirin seeds may fall outside this range, the number of such particles should be minimized, the predominant propor ⁇ tion of the total aspirin seeds being in the about 30 to about 60 mesh size range, particles outside that range being tolerated only to the extent that they do not destroy the relative linearity of release over the required period of at least about eight hours delivery of the aspirin in the gastrointestinal tract.
  • the polymeric coating requires a major component of ethylcellulose and a minor component of hydroxypropyl- cellulose, it being required that the weight ratio of ethylcellulose to hydroxypropylcellulose be at least about 2.5. Accordingly, in one aspect of the present invention it is contemplated that said weight ratio be from about 2.5:1 to about 15:1, with a preferred range being from about 3.5:1 to about 12:1, and still more preferably about 9:1.
  • the combined weight of the poly ⁇ meric coating is from about 3 to about 10% of the total weight of the polymerically coated aspirin crystal, and in a preferred embodiment is about 5% of such total weight.
  • a typical dosage unit form there are present on the order of 1000 polymerically coated aspirin seeds.
  • 700 gm aspirin crystals are placed in a six inch air sus ⁇ pension coating column (Wurster column of manufacture by Glatt, West German) and coated with a mixture of 368 ml polymer solution which contained 29.4 gm ethylcellulose ["Ethocel N-10" (Dow)] and 7.4 gm hydroxypropylcellulose ["Klucel LF" (Hercules) ] and 92 ml methanol.
  • the coat ⁇ ing solution is sprayed at 2.5 bar pressure with the liquid feed rate of 60 ml/minute.
  • the inlet air tem ⁇ perature is about 60°C.
  • the polymerically coated aspirin crystals of Exam ⁇ ple I are tested according to U.S. . XX dissolution procedure.
  • the test comprises a one hour resi ⁇ dence in simulated gastric fluid, followed by residence in simulated intestinal fluid.
  • the following release of aspirin was observed through this testing procedure, confirming the relatively linear release of the aspirin into this simulated gastrointestinal tract for a period of over ten hours: -5-
  • the relatively linear release shown over the ten hour period indicates the use of the polymerically coated aspirin seeds of the present invention for uses requir ⁇ ing a sustained release for a period of at least eight hours.

Abstract

Une forme de dosage d'aspirine à libération entretenue permet l'administration continue d'aspirine dans les voies gastro-intestinales pendant une période de temps d'au moins huit heures. La forme de dosage d'aspirine à libération entretenue comprend une pluralité de cristaux d'aspirine enduits de polymère, chacun desquels comprend une graine d'aspirine. La majorité des graines d'aspirine présente une taille de maille comprise entre 30 et 60 mailles environ. Chaque graine d'aspirine est recouverte individuellement d'un mélange polymère, comprenant de 1,5 à 15 parties en poids environ d'éthylcellulose et environ une partie en poids d'hydroxypropyl cellulose.
PCT/US1983/000928 1982-06-14 1983-06-14 Aspirine a liberation entretenue WO1984000004A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP50239683A JPS59501067A (ja) 1982-06-14 1983-06-14 持続放出アスピリン

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US38818382A 1982-06-14 1982-06-14

Publications (1)

Publication Number Publication Date
WO1984000004A1 true WO1984000004A1 (fr) 1984-01-05

Family

ID=23533032

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1983/000928 WO1984000004A1 (fr) 1982-06-14 1983-06-14 Aspirine a liberation entretenue

Country Status (2)

Country Link
EP (1) EP0111560A4 (fr)
WO (1) WO1984000004A1 (fr)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0153104A2 (fr) * 1984-02-10 1985-08-28 Benzon Pharma A/S Dose à base d'unités multiples enrobées par une couche de diffusion
WO1986004817A1 (fr) * 1985-02-19 1986-08-28 Key Pharmaceuticals, Inc. Chlorure de potassium a liberation controlee
EP0775488A1 (fr) * 1995-11-23 1997-05-28 Mazal Pharmaceutique Composition pharmaceutique stable à base d'acide acétylsalicyclique et de tocophérol
US5855915A (en) * 1995-06-30 1999-01-05 Baylor University Tablets or biologically acceptable implants for long-term antiinflammatory drug release

Citations (19)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2853420A (en) * 1956-01-25 1958-09-23 Lowey Hans Ethyl cellulose coatings for shaped medicinal preparations
US2887440A (en) * 1957-08-12 1959-05-19 Dow Chemical Co Enteric coating
US2928770A (en) * 1958-11-28 1960-03-15 Frank M Bardani Sustained action pill
US3247066A (en) * 1962-09-12 1966-04-19 Parke Davis & Co Controlled release dosage form containing water-swellable beadlet
US3344029A (en) * 1963-06-03 1967-09-26 U S Ethicals Inc Sustained release composition
US3400185A (en) * 1965-04-08 1968-09-03 Bristol Myers Co Agglomeration of smaller pharmaceutical particles into larger microspherules and enteic-coating thereof
US3632739A (en) * 1969-12-29 1972-01-04 Sandoz Ag Solid sustained release pharmaceutical preparation
US3773920A (en) * 1971-07-14 1973-11-20 Nikken Chemicals Co Ltd Sustained release medicinal composition
US3835221A (en) * 1970-03-05 1974-09-10 Hoechst Ag Orally administrable drug dosage form having delayed action
US3917813A (en) * 1973-03-28 1975-11-04 Benzon As Alfred Oral drug preparations
US3981984A (en) * 1968-04-01 1976-09-21 Colorcon Incorporated Color film coating of tablets and the like
US4016254A (en) * 1972-05-19 1977-04-05 Beecham Group Limited Pharmaceutical formulations
US4083949A (en) * 1973-07-17 1978-04-11 Byk Gulden Lomberg Chemische Fabrik Gmbh New oral form of medicament and a method for producing it
US4173626A (en) * 1978-12-11 1979-11-06 Merck & Co., Inc. Sustained release indomethacin
US4321253A (en) * 1980-08-22 1982-03-23 Beatty Morgan L Suspension of microencapsulated bacampicillin acid addition salt for oral, especially pediatric, administration
US4341759A (en) * 1975-11-17 1982-07-27 Aktiebolaget Hassle Granule having controlled release properties
EP0063014A2 (fr) * 1981-04-13 1982-10-20 Sankyo Company Limited Une méthode de préparation des compositions solides enrobées
EP0067595A2 (fr) * 1981-06-02 1982-12-22 Warner-Lambert Company Composition de gomme à mâcher contenant l'ester méthylique enrobé de la L-aspartyl-L-phénylalanine
WO1983000284A1 (fr) * 1981-07-15 1983-02-03 Key Pharma Theophylline a liberation prolongee

Patent Citations (19)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2853420A (en) * 1956-01-25 1958-09-23 Lowey Hans Ethyl cellulose coatings for shaped medicinal preparations
US2887440A (en) * 1957-08-12 1959-05-19 Dow Chemical Co Enteric coating
US2928770A (en) * 1958-11-28 1960-03-15 Frank M Bardani Sustained action pill
US3247066A (en) * 1962-09-12 1966-04-19 Parke Davis & Co Controlled release dosage form containing water-swellable beadlet
US3344029A (en) * 1963-06-03 1967-09-26 U S Ethicals Inc Sustained release composition
US3400185A (en) * 1965-04-08 1968-09-03 Bristol Myers Co Agglomeration of smaller pharmaceutical particles into larger microspherules and enteic-coating thereof
US3981984A (en) * 1968-04-01 1976-09-21 Colorcon Incorporated Color film coating of tablets and the like
US3632739A (en) * 1969-12-29 1972-01-04 Sandoz Ag Solid sustained release pharmaceutical preparation
US3835221A (en) * 1970-03-05 1974-09-10 Hoechst Ag Orally administrable drug dosage form having delayed action
US3773920A (en) * 1971-07-14 1973-11-20 Nikken Chemicals Co Ltd Sustained release medicinal composition
US4016254A (en) * 1972-05-19 1977-04-05 Beecham Group Limited Pharmaceutical formulations
US3917813A (en) * 1973-03-28 1975-11-04 Benzon As Alfred Oral drug preparations
US4083949A (en) * 1973-07-17 1978-04-11 Byk Gulden Lomberg Chemische Fabrik Gmbh New oral form of medicament and a method for producing it
US4341759A (en) * 1975-11-17 1982-07-27 Aktiebolaget Hassle Granule having controlled release properties
US4173626A (en) * 1978-12-11 1979-11-06 Merck & Co., Inc. Sustained release indomethacin
US4321253A (en) * 1980-08-22 1982-03-23 Beatty Morgan L Suspension of microencapsulated bacampicillin acid addition salt for oral, especially pediatric, administration
EP0063014A2 (fr) * 1981-04-13 1982-10-20 Sankyo Company Limited Une méthode de préparation des compositions solides enrobées
EP0067595A2 (fr) * 1981-06-02 1982-12-22 Warner-Lambert Company Composition de gomme à mâcher contenant l'ester méthylique enrobé de la L-aspartyl-L-phénylalanine
WO1983000284A1 (fr) * 1981-07-15 1983-02-03 Key Pharma Theophylline a liberation prolongee

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
CHEMICAL ABSTRACTS, Vol. 98, No. 20 issued 16 May 1983 (Columbus, Ohio, USA) HSIAO, H.C. (Key Pharamaceuticals, Inc.) PCT Int. Appl. Abstract No. 166917c *
See also references of EP0111560A4 *

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0153104A2 (fr) * 1984-02-10 1985-08-28 Benzon Pharma A/S Dose à base d'unités multiples enrobées par une couche de diffusion
EP0153104A3 (en) * 1984-02-10 1985-12-18 A/S Alfred Benzon Diffusion coated multiple-units dosage form
JPH0759500B2 (ja) * 1984-02-10 1995-06-28 ベンツォン ファーマ エイ／エス 拡散被覆された複合単位服用剤
WO1986004817A1 (fr) * 1985-02-19 1986-08-28 Key Pharmaceuticals, Inc. Chlorure de potassium a liberation controlee
US5855915A (en) * 1995-06-30 1999-01-05 Baylor University Tablets or biologically acceptable implants for long-term antiinflammatory drug release
US6280772B1 (en) 1995-06-30 2001-08-28 Baylor University Polyester/carboxylic acid composite materials
EP0775488A1 (fr) * 1995-11-23 1997-05-28 Mazal Pharmaceutique Composition pharmaceutique stable à base d'acide acétylsalicyclique et de tocophérol
FR2741534A1 (fr) * 1995-11-23 1997-05-30 Mazal Pharma Composition pharmaceutique stable a base d'acide acetylsalicylique et de tocopherol

Also Published As

Publication number Publication date
EP0111560A4 (fr) 1987-02-03
EP0111560A1 (fr) 1984-06-27

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