WO1991015194A1 - Taste masking of ibuprofen by fluid bed coating - Google Patents

Taste masking of ibuprofen by fluid bed coating Download PDF

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Publication number
WO1991015194A1
WO1991015194A1 PCT/US1991/001089 US9101089W WO9115194A1 WO 1991015194 A1 WO1991015194 A1 WO 1991015194A1 US 9101089 W US9101089 W US 9101089W WO 9115194 A1 WO9115194 A1 WO 9115194A1
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WO
WIPO (PCT)
Prior art keywords
ibuprofen
composition according
plasticizer
chewable
coating
Prior art date
Application number
PCT/US1991/001089
Other languages
French (fr)
Inventor
Robert Wu-Wei Shen
Original Assignee
The Upjohn Company
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 The Upjohn Company filed Critical The Upjohn Company
Priority to SU5053248A priority Critical patent/RU2101010C1/en
Priority to JP91504575A priority patent/JPH05506011A/en
Priority to EP91904188A priority patent/EP0524180B1/en
Priority to DE69109282T priority patent/DE69109282T2/en
Publication of WO1991015194A1 publication Critical patent/WO1991015194A1/en
Priority to NO923947A priority patent/NO300758B1/en
Priority to FI924589A priority patent/FI924589A0/en
Priority to US08/469,715 priority patent/US5552152A/en

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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
    • A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
    • A61K9/2077—Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
    • A61K9/2081—Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets with microcapsules or coated microparticles according to A61K9/50
    • 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
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • 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
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
    • 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
    • A61K9/5026—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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/04—Centrally acting analgesics, e.g. opioids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]

Definitions

  • Ibuprofen is a well-known therapeutic agent. Its therapeutic activities include analgesia and anti-pyretic attack. As with most medicines, one of the difficulties with ibuprofen is in making it palatable to children. This difficulty has been overcome with most medicines by preparing formulations such as syrups and drops.
  • the present invention relates to chewable tablets that are palatable to children and a process for making the tablets.
  • Ibuprofen and its use for treatment of analgesia is disclosed in U.S. patent 3,385,886.
  • Compositions containing ibuprofen and methods for using them are described in U.S. patent 3,228,831.
  • New crystalline and high dose formulations of ibuprofen are disclosed in U.S. patents 4,476,248 and 4,609,675 respectively.
  • Microencapsulation is described by J.A. Bakan, Part Three of "The Theory and
  • EUDRAGIT L30D is a known polymer useful for coating orally administered pharmaceutical dosage forms, particularly tablets, capsules and pills, with coatings which are resistant to gastric juices but solvent in intestinal juices.
  • Chewable taste-masked pharmaceutical compositions, including some containing ibuprofen, are described in U.S. patent 4,800,087. However, the compositions described therein require a coating consisting of a mixture of polymers. The use of fluidized bed for coating pharmaceutical products is described in U.S. Patent 4,800,087.
  • a chewable taste-masked tablet having controlled release characteristics comprising a microcapsule of about 100 microns to about 0.8 mm in diameter having (a) a pharmaceutical core including crystalline ibuprofen and (b) a methacrylic acid copolymer coating having sufficient elasticity to withstand chewing.
  • the present invention comprises formulations of taste-masked microcapsules which further comprise (a) a pharmaceutical core of crystalline ibuprofen and (b) a methacrylic acid copolymer coating that may provide chewable taste-masked characteris- tics.
  • Both the polymeric coating and the pharmaceutical core may further comprise diluents, fillers and other pharmaceutical additives which may effect the rate pf release of active ibuprofen from the microcapsule.
  • the methacrylic acid copolymer is preferably dispersable in water so as to take advantage of aqueous formulation techniques and has a rapid rate of dissolution at a pH of about 5.5.
  • Aqueous-based coating systems are safe and make regulatory compliance (EPA) relatively easy compared to non-aquaous based coating systems.
  • An elastic microcapsule which will not release ibuprofen in the mouth when chewed is contemplated by the present invention.
  • a preferred coating composition is a high temperature film forming polymer or "hard" polymer.
  • a hard polymer is defined as a polymer that will form a film on a pharmaceutical core at a temperature of at least about 30°C.
  • high temperature film forming polymers useful in this invention include hydroxypropylmethyl cellulose, for example, Pharmacoat' 606 brand from Shinetro Corp., Tokyo, Japan, hydroxypropyl cellulose, for example, Klucel' brand from Hercules Corp., Wilmington, Del. , methylcellulose for example Methocel A% from Dow Chemical, Midland, Mich.
  • ethylcellulose for example, Ethocel' brand from Dow Chemical Corp., and other aqueous polymeric dispersions such as Aquacost' Brand from FMC, Philadelphia, PA., and Surelease' brand from Colorcon, West Point, PA., polyvinyl alcohol, polyvinyl acetate, cellulose acetate butyrate, styrene acylate copolymers, for example Janocryl 138 (61 °C. film forming copolymer from S.C. Johnson, Racine, Wis.) and copolymers of acrylic acid esters, for example, the EUDRAGIT Copolymers (Rohm Phar a GmbH Westerstadt, W. Germany): Eudragit' L30D, Eudragit' L100-55, Eudragit' RS(30D and 100).
  • EUDRAGIT Copolymers Roshm Phar a GmbH Westerstadt, W. Germany
  • Eudragit' copolymers that are preferred in embodiments of this invention include L30D, an anionic copolymer based of polymethacrylic and acrylic acid esters (Methacrylic Acid Copolymer, Type C in USP XX-L/NF XVI) with a mean molecular weight of 250,000.
  • the polymeric coating should provide for immediate release characteristics, i.e. , rapid release of the active agents in the duodenum within a period of about one hour.
  • the microcapsules are formulated into chewable, taste-masked oral tablets or capsules, the formulations provide for immediate, rapid release in the stomach.
  • the chewable polymeric coating providing immediate release upon reaching the duodenum i.e. , within one hour after ingestion may be comprised of a pharmaceutically compatible high temperature film forming polymer that is water insoluble or not swellable within thepH range (about 5.5-6.5) and or the liquid content of the mouth and will not release the active agent in the mouth, but will dissolve or change in physical character in the duodenum, for example, swell or become more porous, thus releasing drug.
  • EUDRAGIT L30D The most preferred film forming acrylic resin polymer that releases active agent rapidly in duodenum is EUDRAGIT L30D.
  • EUDRAGIT L30D is a copolymer anionic in character, based on polymethacrylic acid and acrylic acid esters.
  • EUDRAGIT L30D is soluble at pH's in the mouth and insoluble at pH's of the stomach, it has found usefulness in chewable, taste-masked immediate release formulations of the present invention. This usefulness may stem from the lack of liquid in the mouth, or may be the result of elastic qualities that EUDRAGIT L30D acquires when formulated in combination with a plasticizer, or preferably, with EUDRAGIT E30D.
  • plasticizers may be incorporated into the coatings.
  • Plasticizers useful to provide the requisite elasticity include propylene glycol and polyalkylene glycols, for example, polyethylene glycol, triacetin, (glyceryl triacetate from Eastman Kodak, Rochester, NY vinyl pyrrolidone, diethyl phthallate, dibutylsebacate, and esters of citric acid among others.
  • the plasticizers comprise between about 2% and about 50% by weight of polymer and plasticizer combined, preferably between about 5% and 15% by weight and most preferably about 10% by weight of the polymer and plasticizer combined.
  • the chewable tablets of this invention are prepared by spraying a solution of the methacrylic acid copolymer on to a fluidized bed of crystalline ibuprofen.
  • Crystalline ibuprofen can be prepared by the process described in U.S. Patent 4,476,248.
  • the particle size of the ibuprofen should be about 80 to 500 microns and it it may contain excipients such as starch, lactose, hydroxypropyl methylcellulose, microcrystalline cellulose PVP, sucrose and fructose.
  • the residence time should be such that the ratio of copolymer to ibuprofen of each chewable tablet is about eight percent by weight.
  • the temperature of the inlet and outlet air should be maintained between 40 and 60 C. 20 and 40 C. respectively.
  • the preferred inlet and outlet air temperatures are between 45 and 55 and 33 and 27°C respectively.
  • the temperature of the fluidized bed should be maintained between 60 and 20 p respectively.
  • the preferred temperature of the bed is about 35 C.
  • the amount of ENDRAGIT L30D in the encapsulation formulation should be between about 10% to 60% by weight of ibuprofen, preferably about 14%.
  • Ibuprofen crystals (particle size #40-105) are air suspended in a closed chamber (Glatt GPCG5).
  • An aqueous dispersion of Eudragit L 30D and talc is sprayed onto the fluidized bed of ibuprofen at a rate of 60gm/min.
  • the inlet and outlet air temperature are maintained at 50°C. and 20-22°C. respectively.
  • the air rate is adjusted so as to maintain the particles in a suspended state and to maintain the fluidized bed at a tempera ⁇ ture of 35 °C.
  • Table 1 shows a comparison of dissolution data between MOTRIN IB Tablet in PH 7.2 and the MOTRIN Chewable Tablets of this invention.
  • Table 2 shows a comparison of dissolution data between MOTRIN IB Tablets in and the MOTRIN Chewable Tablets of this invention.
  • Formula #12, #13 and Motrin IB shows the same reline forte after 10 minutes.
  • Formula #12, #13 all pass U.S. P. Tablets specification 20 minutes 785%.
  • Flask 1 Motrin IB.
  • Flask 2 Motrin chewable experiment Lot 12.
  • Flask 3 Motrin chewable experiment Lot 13.
  • Flask 4 Recrystallized Ibuprofen.
  • Flask 1 Motrin IB.
  • Flask 2 Motrin chewable experiment Lot 12.
  • Flask 3 Motrin chewable experiment Lot 13.
  • Flask 4 Recrystallized Ibuprofen.

Abstract

A chewable taste-masked ibuprofen tablet having controlled release characteristics.

Description

TASTE MASKING OF IBUPROFEN BY FLUID BED COATING BACKGROUND OF THE INVENTION Ibuprofen is a well-known therapeutic agent. Its therapeutic activities include analgesia and anti-pyretic attack. As with most medicines, one of the difficulties with ibuprofen is in making it palatable to children. This difficulty has been overcome with most medicines by preparing formulations such as syrups and drops. The present invention relates to chewable tablets that are palatable to children and a process for making the tablets.
From a manufacturing cost standpoint, it is desirable to have chewable, taste- masked microcapsules that are large (0.25-1 mm in diameter), because larger microcapsules are easier to manufacture and package, and are less expensive to produce than are small microcapsules. However, an increase in size makes fracture during chewing and the release of drug from the microcapsule more likely to occur especially when there is an inadequate amount of plasticizer or other component included to provide elasticity. A larger sized microcapsule requires greater elasticity to minimize the likelihood that a fracture will occur and active agent will be released. There is therefore a need in the art of pharmaceutical formulation to provide encapsulating coatings capable of being formulated into chewable microcapsules as large as about 1.5 mm. that will not release drugs during chewing. INFORMATION DISCLOSURE
Ibuprofen and its use for treatment of analgesia is disclosed in U.S. patent 3,385,886. Compositions containing ibuprofen and methods for using them are described in U.S. patent 3,228,831. New crystalline and high dose formulations of ibuprofen are disclosed in U.S. patents 4,476,248 and 4,609,675 respectively. Microencapsulation is described by J.A. Bakan, Part Three of "The Theory and
Practice of Industrial Pharmacy", 1986, pp. 413-429.
EUDRAGIT L30D is a known polymer useful for coating orally administered pharmaceutical dosage forms, particularly tablets, capsules and pills, with coatings which are resistant to gastric juices but solvent in intestinal juices. Chewable taste-masked pharmaceutical compositions, including some containing ibuprofen, are described in U.S. patent 4,800,087. However, the compositions described therein require a coating consisting of a mixture of polymers. The use of fluidized bed for coating pharmaceutical products is described in U.S. Patent 4,800,087. SUMMARY OF THE INVENTION This invention involves:
A chewable taste-masked tablet having controlled release characteristics comprising a microcapsule of about 100 microns to about 0.8 mm in diameter having (a) a pharmaceutical core including crystalline ibuprofen and (b) a methacrylic acid copolymer coating having sufficient elasticity to withstand chewing.
While chewable taste masked formulations of ibuprofen are referred to in the prior art, among the advantages of the compositions of this invention over the closest prior art compositions is that the coating used consists of a single copolymer rather than a mixture of copolymers.
DETAILED DESCRIPTION OF THE INVENTION The present invention comprises formulations of taste-masked microcapsules which further comprise (a) a pharmaceutical core of crystalline ibuprofen and (b) a methacrylic acid copolymer coating that may provide chewable taste-masked characteris- tics. Both the polymeric coating and the pharmaceutical core may further comprise diluents, fillers and other pharmaceutical additives which may effect the rate pf release of active ibuprofen from the microcapsule.
The methacrylic acid copolymer is preferably dispersable in water so as to take advantage of aqueous formulation techniques and has a rapid rate of dissolution at a pH of about 5.5.. Aqueous-based coating systems are safe and make regulatory compliance (EPA) relatively easy compared to non-aquaous based coating systems. An elastic microcapsule which will not release ibuprofen in the mouth when chewed is contemplated by the present invention.
A preferred coating composition is a high temperature film forming polymer or "hard" polymer. A hard polymer is defined as a polymer that will form a film on a pharmaceutical core at a temperature of at least about 30°C. Examples of high temperature film forming polymers useful in this invention include hydroxypropylmethyl cellulose, for example, Pharmacoat' 606 brand from Shinetro Corp., Tokyo, Japan, hydroxypropyl cellulose, for example, Klucel' brand from Hercules Corp., Wilmington, Del. , methylcellulose for example Methocel A% from Dow Chemical, Midland, Mich. , ethylcellulose, for example, Ethocel' brand from Dow Chemical Corp., and other aqueous polymeric dispersions such as Aquacost' Brand from FMC, Philadelphia, PA., and Surelease' brand from Colorcon, West Point, PA., polyvinyl alcohol, polyvinyl acetate, cellulose acetate butyrate, styrene acylate copolymers, for example Janocryl 138 (61 °C. film forming copolymer from S.C. Johnson, Racine, Wis.) and copolymers of acrylic acid esters, for example, the EUDRAGIT Copolymers (Rohm Phar a GmbH Westerstadt, W. Germany): Eudragit' L30D, Eudragit' L100-55, Eudragit' RS(30D and 100).
Eudragit' copolymers that are preferred in embodiments of this invention include L30D, an anionic copolymer based of polymethacrylic and acrylic acid esters (Methacrylic Acid Copolymer, Type C in USP XX-L/NF XVI) with a mean molecular weight of 250,000. The polymeric coating should provide for immediate release characteristics, i.e. , rapid release of the active agents in the duodenum within a period of about one hour. When the microcapsules are formulated into chewable, taste-masked oral tablets or capsules, the formulations provide for immediate, rapid release in the stomach.
The chewable polymeric coating providing immediate release upon reaching the duodenum i.e. , within one hour after ingestion may be comprised of a pharmaceutically compatible high temperature film forming polymer that is water insoluble or not swellable within thepH range (about 5.5-6.5) and or the liquid content of the mouth and will not release the active agent in the mouth, but will dissolve or change in physical character in the duodenum, for example, swell or become more porous, thus releasing drug.
The most preferred film forming acrylic resin polymer that releases active agent rapidly in duodenum is EUDRAGIT L30D. EUDRAGIT L30D is a copolymer anionic in character, based on polymethacrylic acid and acrylic acid esters. Although EUDRAGIT L30D is soluble at pH's in the mouth and insoluble at pH's of the stomach, it has found usefulness in chewable, taste-masked immediate release formulations of the present invention. This usefulness may stem from the lack of liquid in the mouth, or may be the result of elastic qualities that EUDRAGIT L30D acquires when formulated in combination with a plasticizer, or preferably, with EUDRAGIT E30D.
Any of the above described high-temperature film-forming polymers may be used for microencapsulation. However, to make capsules of the required elasticity using the above described high temperature film forming polymers, plasticizers may be incorporated into the coatings. Plasticizers useful to provide the requisite elasticity include propylene glycol and polyalkylene glycols, for example, polyethylene glycol, triacetin, (glyceryl triacetate from Eastman Kodak, Rochester, NY vinyl pyrrolidone, diethyl phthallate, dibutylsebacate, and esters of citric acid among others. Generally, the plasticizers comprise between about 2% and about 50% by weight of polymer and plasticizer combined, preferably between about 5% and 15% by weight and most preferably about 10% by weight of the polymer and plasticizer combined.
The chewable tablets of this invention are prepared by spraying a solution of the methacrylic acid copolymer on to a fluidized bed of crystalline ibuprofen.
Crystalline ibuprofen can be prepared by the process described in U.S. Patent 4,476,248. The particle size of the ibuprofen should be about 80 to 500 microns and it it may contain excipients such as starch, lactose, hydroxypropyl methylcellulose, microcrystalline cellulose PVP, sucrose and fructose.
The residence time should be such that the ratio of copolymer to ibuprofen of each chewable tablet is about eight percent by weight.
The temperature of the inlet and outlet air should be maintained between 40 and 60 C. 20 and 40 C. respectively. The preferred inlet and outlet air temperatures are between 45 and 55 and 33 and 27°C respectively.
The temperature of the fluidized bed should be maintained between 60 and 20p respectively. The preferred temperature of the bed is about 35 C.
The amount of ENDRAGIT L30D in the encapsulation formulation should be between about 10% to 60% by weight of ibuprofen, preferably about 14%.
EMBODIMENT OF THE INVENTION Example I Preparation of chewable ibuprofen tablet (#13, p 23)
A. Encapsulated Ibuprofen
Ibuprofen 4 Kg Eudragit L30D 2.33 Kg (coating polymer)
Propylene Glycol 140 gm (plasticizer)
Talc 200 gm
Purified Water 200 gm
Ibuprofen crystals (particle size #40-105) are air suspended in a closed chamber (Glatt GPCG5). An aqueous dispersion of Eudragit L 30D and talc is sprayed onto the fluidized bed of ibuprofen at a rate of 60gm/min. The inlet and outlet air temperature are maintained at 50°C. and 20-22°C. respectively. The air rate is adjusted so as to maintain the particles in a suspended state and to maintain the fluidized bed at a tempera¬ ture of 35 °C. Air Atomizing Pressure 3.5 bar
B. w
Figure imgf000007_0001
The compression mix of above was tabletted on a Manesty beta press with 1/2" flat face tooling. Tablet weight: 813 mg. Hardness: 9 - 13 Strong Cobert (SC). Disintegration Time in water: 2 minutes.
Table 1 shows a comparison of dissolution data between MOTRIN IB Tablet in PH 7.2 and the MOTRIN Chewable Tablets of this invention. Table 2 shows a comparison of dissolution data between MOTRIN IB Tablets in and the MOTRIN Chewable Tablets of this invention.
TABLE I
Comparison of Dissolution Data between Motrin IB and Motrin Chewable Tablets
Figure imgf000009_0001
Formula #12, #13 and Motrin IB shows the same reline forte after 10 minutes. Formula #12, #13 all pass U.S. P. Tablets specification 20 minutes 785%.
Flask 1: Motrin IB.
Flask 2: Motrin chewable experiment Lot 12.
Flask 3: Motrin chewable experiment Lot 13.
Flask 4: Recrystallized Ibuprofen.
TABLE II
Figure imgf000011_0001
PH 5-8: After 10 minutes about 10-12% difference action compare #12, #13 with Motrin IB.
After 20 minutes about 7-8% difference when compared #12, and #13 with Motrin IB.
After 30 minutes shows no significant difference among them. Flask 1: Motrin IB.
Flask 2: Motrin chewable experiment Lot 12.
Flask 3: Motrin chewable experiment Lot 13.
Flask 4: Recrystallized Ibuprofen.

Claims

1. A chewable taste-masked tablet having controlled release characteristics comprising a microcapsule of about 100 microns to about 0.8 mm in diameter having (a) a pharmaceutical core including crystalline ibuprofen and (b) a methacrylic acid copolymer coating having sufficient elasticity to withstand chewing.
2. A chewable taste-masked pharmaceutical composition according to claim 1 wherein the copolymer is Eudragit L30D said coating being adapted to release said ibuprofen in the duodenum.
3. The composition according to claim 1, wherein said copolymer coating further comprises a plasticizer.
4. The composition according to claim 2, wherein said copolymer coating further comprises a plasticizer.
5. The composition according to claim 4, wherein said plasticizer is selected from the group consisting of glyceryl triacetate, triethyl citrate, acetyl triethyl citrate, dibutyl sebcate, acetyl tributyl citrate, diethyl phthlate, dibutyl phthlate, glycerine, propylene glycol and polyethylene glycol.
6. The composition according to claim 5 wherein said plasticizer is propylene glycol.
PCT/US1991/001089 1990-04-11 1991-02-26 Taste masking of ibuprofen by fluid bed coating WO1991015194A1 (en)

Priority Applications (7)

Application Number Priority Date Filing Date Title
SU5053248A RU2101010C1 (en) 1990-04-11 1991-02-26 Taste ibuprofen masking with polymer coating
JP91504575A JPH05506011A (en) 1990-04-11 1991-02-26 Taste masking of ibuprofen by fluidized bed coating
EP91904188A EP0524180B1 (en) 1990-04-11 1991-02-26 Taste masking of ibuprofen by fluid bed coating
DE69109282T DE69109282T2 (en) 1990-04-11 1991-02-26 METHOD FOR FLAVORING IBUPROFEN.
NO923947A NO300758B1 (en) 1990-04-11 1992-10-09 Process for the preparation of a chewable, flavor-masked tablet having controlled release properties
FI924589A FI924589A0 (en) 1990-04-11 1992-10-09 SMAKMASKERING AV IBUPROFEN MED VIRVELBAEDDBETAECKNING
US08/469,715 US5552152A (en) 1990-04-11 1995-06-06 Taste masking of ibuprofen by fluid bed coating

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US50819390A 1990-04-11 1990-04-11
US508,193 1990-04-11

Publications (1)

Publication Number Publication Date
WO1991015194A1 true WO1991015194A1 (en) 1991-10-17

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Country Status (14)

Country Link
US (1) US5552152A (en)
EP (1) EP0524180B1 (en)
JP (1) JPH05506011A (en)
AT (1) ATE121619T1 (en)
AU (1) AU639988B2 (en)
CA (1) CA2076983A1 (en)
DE (1) DE69109282T2 (en)
DK (1) DK0524180T3 (en)
ES (1) ES2071986T3 (en)
FI (1) FI924589A0 (en)
HU (2) HUT64220A (en)
NO (1) NO300758B1 (en)
RU (1) RU2101010C1 (en)
WO (1) WO1991015194A1 (en)

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FR2785539A1 (en) * 1998-11-06 2000-05-12 Prographarm Laboratoires PARTICLES COATED WITH GRANULAR CRYSTALLINE IBUPROFEN
FR2785538A1 (en) * 1998-11-06 2000-05-12 Prographarm Laboratoires PERFECTED QUICK DELIVERY TABLET
WO2001012161A1 (en) * 1999-08-17 2001-02-22 Novartis Consumer Health S.A. Rapidly dissolving dosage form and process for making same
US8124124B2 (en) 1999-12-09 2012-02-28 Reckitt Benckiser Healthcare (Uk) Limited Compressed tablet formulation comprising non-steroidal anti-inflammatory drugs and methods
US8617587B2 (en) 2002-03-11 2013-12-31 Novartis Ag Tasted masked veterinary solid compositions

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FR2766089B1 (en) * 1997-07-21 2000-06-02 Prographarm Lab IMPROVED MULTIPARTICULAR TABLET WITH RAPID DELIVERY
CN1123573C (en) * 1997-11-12 2003-10-08 拜尔公司 2-phenyl substituted imidazotriazinones as phosphodiesterase inhibitors
US6270807B1 (en) 1999-03-02 2001-08-07 L. Perrigo Company Taste-masked pharmaceutical composition
BR0009557A (en) 1999-04-06 2002-05-28 Ethypharm Lab Prod Ethiques Pharmaceutical suspension for ibuprofen drinking
EP1276470B1 (en) 2000-04-20 2007-05-02 Novartis AG Taste masking coating composition
US6551617B1 (en) 2000-04-20 2003-04-22 Bristol-Myers Squibb Company Taste masking coating composition
ES2278927T3 (en) * 2001-05-09 2007-08-16 Bayer Healthcare Ag NEW USE OF IMIDAZOTRIAZINONES 2- (2-ETOXI-5- (4-METHYL-PIPERAZIN-1-SULPHONYL) -PHENYL) -5-METHYL-7-PROPIL-3H-IMIDAZO (5,1-F) (1, 2,4) TRIAZIN-4-ONA.
ATE424812T1 (en) * 2001-08-01 2009-03-15 Novartis Ag COMPOSITION FOR TASTE MASKING
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EP0524180B1 (en) 1995-04-26
DK0524180T3 (en) 1995-09-04
NO923947L (en) 1992-10-09
NO300758B1 (en) 1997-07-21
DE69109282T2 (en) 1995-09-28
FI924589A (en) 1992-10-09
ES2071986T3 (en) 1995-07-01
HUT64220A (en) 1993-12-28
RU2101010C1 (en) 1998-01-10
ATE121619T1 (en) 1995-05-15
FI924589A0 (en) 1992-10-09
DE69109282D1 (en) 1995-06-01
JPH05506011A (en) 1993-09-02
NO923947D0 (en) 1992-10-09
US5552152A (en) 1996-09-03
AU7256091A (en) 1991-10-30
HU9203193D0 (en) 1992-12-28
AU639988B2 (en) 1993-08-12
EP0524180A1 (en) 1993-01-27
HU211247A9 (en) 1995-11-28
CA2076983A1 (en) 1991-10-12

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