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WO1994010994A1 - Compositions effervescentes de sel d'ibuprofene - Google Patents

Compositions effervescentes de sel d'ibuprofene Download PDF

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Publication number
WO1994010994A1
WO1994010994A1 PCT/EP1993/003207 EP9303207W WO9410994A1 WO 1994010994 A1 WO1994010994 A1 WO 1994010994A1 EP 9303207 W EP9303207 W EP 9303207W WO 9410994 A1 WO9410994 A1 WO 9410994A1
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WO
WIPO (PCT)
Prior art keywords
composition
isobutylphenyl
propionic acid
pharmaceutically acceptable
microns
Prior art date
Legal status (The legal status 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 status listed.)
Ceased
Application number
PCT/EP1993/003207
Other languages
English (en)
Inventor
Kenneth Donald Vaughan
Ian Ashley Price
David Edward Askew
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Boots Co PLC
Original Assignee
Boots Co PLC
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 Boots Co PLC filed Critical Boots Co PLC
Priority to AU54660/94A priority Critical patent/AU5466094A/en
Publication of WO1994010994A1 publication Critical patent/WO1994010994A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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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
    • A61K31/185—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
    • A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
    • A61K9/0007—Effervescent

Definitions

  • compositions for oral administration comprising water soluble pharmaceutically acceptable salts of 2-(4- isobutylphenyDpropionic acid and stereoisomers thereof.
  • the compositions of the invention effervesce when added to water to form an aqueous solution of the pharmaceutically acceptable salt of 2- (4- isobutylphenyDpropionic acid.
  • Racemic 2- (4-isobutylphenyl)propionic acid which is also known as ibuprofen, is a well known medicament with anti-inflammatory, antipyretic and analgesic activities.
  • Known uses of 2-(4-isobutylphenyl)propionic acid include the treatment of pain and inflammation in musculoskeletal disorders such as rheumatic disease, and the treatment of pain in a variety of other disorders, for example headache, neuralgia and dys enorrhoea.
  • 2- (4-Isobutylphenyl)propionic acid contains a single chiral centre at an asymmetrically substituted carbon atom, and therefore exists in two enantiomeric forms: S(+)2- (4-isobutylphenyl)propionic acid (dexibuprofen) and R(-)2-(4-isobutylphenyDpropionic acid. It will be understood that the term 2- (4- isobutylphenyDpropionic acid as used herein includes either enantiomer separately or any mixture thereof including a racemic mixture.
  • Aqueous solutions of 2- ( -isobutylphenyDpropionic acid salts are convenient in use and are advantageous for those patients, often children and the elderly, who have difficulty in swallowing tablets or capsules.
  • 2 - (4-IsobutylphenyDpropionic acid particularly when present in its free acid form or in an aqueous suspension has an unpleasant taste with a burning sensation in the throat. Therefore, it is an object of the present invention to produce a powder or tablet composition containing a 2- (4-isobutylphenyl)propionic acid salt which effervesces when added to water to produce a clear solution, and which has no unpleasant taste sensation and to provide a simplified method of producing the same.
  • 2-(4-IsobutylphenyDpropionic acid salts may be produced by reaction between 2- (4-isobutylphenyl) - propionic acid and the corresponding base followed by crystallisation of the required salt.
  • 2- (4-isobutylphenyl) - propionic acid For example reacting sodium hydroxide with 2- (4-isobutylphenyl) - propionic acid produces sodium 2- (4-isobutylphenyl) - propionate.
  • the resulting sodium salt is typically a flaky coarse crystalline solid material, which is milled to produce a finer powder having a crystal size typically less than 100 microns.
  • a fine powder was considered necessary for use in simple effervescent compositions as it was believed that a fine powder gave a faster dissolution rate than a material having a larger crystal size which it was thought could not be used directly in simple effervescent compositions.
  • Such fine powders are known to be formulated into effervescent tablet compositions, for example in compositions described in the applicant's European Patent Application 0228164.
  • a disadvantage of using a fine powder in the production of ibuprofen tablets is that once granulated and dried, a fine powder has a tendency to produce a sticky non flowing mass which will not flow freely into tablet dies and can obstruct the dies.
  • an ibuprofen salt which is a fine powder ( ⁇ 100 microns) is a difficult material to handle particularly when tabletting.
  • Others have also sought to produce satisfactory effervescent compositions of ibuprofen or a salt thereof.
  • European Patent Application 0351353 (Aesculapuis Pharma) and documents on the public file thereof teach that effervescent compositions comprising particular ranges of ingredients of ibuprofen or its sodium salt, sodium bicarbonate and citric acid should be mixed in a particular manner, not being admixed in a single phase. There is no teaching in this document of use of a particular crystal size of ibuprofen or its sodium salt.
  • European Patent Application 0369228 discloses a granulated composition requiring various proportions of a water soluble ibuprofen salt, excipient, stabiliser, sodium or potassium carbonate and an acid component.
  • This composition comprises many expensive ingredients for example stabilisers such as water soluble polymers.
  • stabilisers such as water soluble polymers.
  • European Patent Application 0203768 discloses effervescent compositions comprising a pre-blended mixture of a granulated therapeutic agent having a particle size of between 100 and 600 microns and a component of a first effervescent system having a similar particle size, the pre-blend being mixed with a second effervescent system.
  • the use of two effervescent systems and the pre-blending of the therapeutic agent results in compositions which are expensive and complicated to prepare.
  • the therapeutic agents disclosed include non-steroidal anti-inflammatory drugs such as acetaminophen, aspirin and ibuprofen.
  • compositions described in this document do not provide satisfactory effervescent formulations, when ibuprofen is used as the therapeutic agent.
  • compositions of the present invention also have the advantage of using inexpensive and readily available ingredients which can simply be blended together in intimate admixture in a single step to form powder or tablet compositions, without requiring complicated processing steps.
  • Aqueous solutions formed by the compositions of the present invention contain negligible amounts of 2-(4- isobutylphenyl)propionic acid as its free acid.
  • 2-(4- isobutylphenyl)propionic acid as its free acid.
  • the unpleasant taste of 2-(4- isobutylphenyDpropionic acid is largely absent from aqueous solutions formed by the compositions of the present invention.
  • the present invention provides a pharmaceutical powder or tablet composition
  • a pharmaceutically acceptable salt of 2- (4- isobutylphenyl)propionic acid as either enantiomer separately or any mixture thereof, in intimate admixture with a pharmaceutically acceptable couple comprising at least one acid component and at least one carbonate component, the couple producing carbon dioxide in the presence of water; in which 95% or more of the 2-(4- isobutylphenyl) -propionic acid salt has a crystal size, as defined hereinafter, from 180 microns to 800 microns; and further in which the carbonate component of the couple is present in an amount from two to six times by weight the amount of acid component of the couple, such that the pH of an aqueous solution formed from 1 g of the composition in 100 ml of purified water is greater than 5.0.
  • 2- (4-Isobutylphenyl)propionic acid may form salts with organic or inorganic bases in a conventional manner.
  • Particularly suitable salts of 2-(4- isobutylphenyl)propionic acid include, for example, alkali metal salts (such as sodium and potassium salts) , alkaline earth metal salts (such as magnesium and calcium salts), aluminium and ammonium salts, salts with suitable organic bases such as alkylamines, N-methyl-D- glucamine and salts with amino acids such as arginine and lysine. It will be readily understood that these salts may also exist as racemates, separate enantiomers or mixtures thereof.
  • 2- (4-isobutylphenyl) - propionic acid salt is defined herein as either enantiomer separately or any mixture thereof including a racemic mixture, of all pharmaceutically acceptable salts of 2-(4-isobutylphenyl)propionic acid that are soluble in water.
  • a preferred salt is sodium 2-(4- isobutylphenyDpropionate, more preferably S(-) sodium 2- (4-isobutylphenyDpropionate.
  • 2-(4-Isobutylphenyl)propionic acid and its salts may exist in more than one crystal form and references to them herein include each crystal form and mixtures thereof.
  • 2-(4-Isobutylphenyl)propionic acid and its salts may also exist in the form of solvates, for example hydrates such as the dihydrate, and references to them herein include each solvate and mixtures thereof.
  • the composition of the present invention comprises from about 1% to about 99% (w/w) of the 2- (4-isobutylphenyl)propionic acid salt, more preferably from about 5% to about 30% (w/w) , most preferably from about 5% to about 10% (w/w) .
  • ' (w/w) ' signifies that the percentages referred to are the percentage weight (or mass) of the ingredient relative to the total weight (or mass) of the composition.
  • Pharmaceutically acceptable effervescent couples that produce carbon dioxide in the presence of water may comprise one or more of the following pharmaceutically acceptable acids which are solid at room temperature, for example one or more of the organic acids: citric, tartaric, adipic or malic, together with one or more carbonate component which is defined herein as a pharmaceutically acceptable organic or inorganic carbonate salt which is solid at room temperature, such as one or more of any of the following: sodium carbonate, sodium bicarbonate, potassium carbonate and potassium bicarbonate.
  • the effervescent couple may comprise as each component separately one or more acid and/or one or more carbonate salt, provided the separate acid and/or carbonate salt mixtures are blended to be homogeneous.
  • the composition comprises one acid as the acid component and one carbonate salt as the carbonate component, more preferably one acid component and one carbonate component.
  • the composition may comprise from about 40% to about 99% (w/w) couple ingredients, more preferably from about 50% to about 95% (w/w) , most preferably from about 75% to about 95% (w/w) .
  • Water soluble salts of 2-(4-isobutylphenyl) - propionic acid can react with the acid component of the couple in the presence of water to precipitate 2- (4- isobutylphenyl)propionic acid. Therefore, to minimise precipitation of 2- (4-isobutylphenyl)propionic acid, the carbonate component and acid component of the couple are present in a respective ratio by weight of from about two to about six, more preferably from about three to about five, most preferably about four.
  • about 95% or more of the 2- (4- isobutylphenyl)propionic acid salt has a crystal size from about 250 microns to about 600 microns, more preferably from about 300 microns to about 500 microns.
  • Crystal size is defined herein to be the length of a crystal measured along its longest axis. Measurement may be made by any suitable method, for example that described in Example 1, below. The range of crystal sizes of the 2-(4-isobutylphenyl)propionic acid salt can be determined by sieve separation. The crystal sizes can then be measured by microscopic image analysis, in comparison with standards supplied by the National Physics Laboratory.
  • the pH of an aqueous solution formed from the composition of the present invention at a concentration of about 1 g of the composition in about 100 ml of purified water is greater than about 5.0, more preferably from about 6.0 to about 9.0, most preferably from about 7.0 to about 8.0.
  • the composition of the present invention is a tablet
  • the composition comprises a pharmaceutically acceptable surface active agent preferably from a trace amount to about 10% (w/w) , more preferably from about 0.01% to about 5% (w/w), most preferably from about 0.1% to about 1% (w/w) .
  • the surface active agent used in the above tablet composition may ionic or non-ionic. Such an agent is present to disperse the active ingredient within the tablet and to prevent grit forming at the surface of the tablet.
  • the surface active agent may have the function of a lubricant or alternatively a separate lubricant may be added.
  • the surface active agent may be a solid or liquid and one or more surface active agents can be used.
  • a suitable surface active agent which also acts as lubricant, is sodium lauryl sulphate.
  • a tablet composition of the present invention comprises from a trace amount to about 10% (w/w) of a separate lubricant, more preferably from about 0.01% to about 5% (w/w), most preferably from about 0.1% to about 1% (w/w).
  • ingredients which may be added to a powder or tablet composition of the present invention include; intense sweeteners such as aspartame, or saccharin, flavour components for example mints such as peppermint; colorants for example brilliant blue FC1 or Cl food blue (as identified in the standard colour index book) ; and to a tablet composition, compression agents such as sorbitol or lactose which increase the hardness of the tablet.
  • intense sweeteners such as aspartame, or saccharin
  • flavour components for example mints such as peppermint
  • colorants for example brilliant blue FC1 or Cl food blue (as identified in the standard colour index book)
  • compression agents such as sorbitol or lactose which increase the hardness of the tablet.
  • the type and quantity of such ingredients are selected to be readily soluble in water, and to minimise the effect on the pH of the aqueous solution formed when compositions of the invention are added to water.
  • these optional ingredients separately comprise from a trace amount to about 20% w/w of the composition, more preferably from
  • a further optional component in the compositions of the present invention is a water scavenging agent to absorb any water remaining after the granulation step and prevent premature effervescence of the composition.
  • a water scavenging agent may be sodium or potassium carbonate especially if already present in the composition as the carbonate component, in which case no additional water scavenging agent need be added.
  • Effervescent compositions of the present invention may optionally comprise other pharmacologically active ingredients and/or enhancing agents compatible with the 2-(4-isobutylphenyl)propionic acid salt.
  • the 2-(4-isobutylphenyl)propionic acid salt may be combined with one or more additional pharmacologically active ingredient or ingredients commonly used in cough or cold remedies, selected from; an antihistamine; caffeine and/or another xanthine derivative; a cough suppressant; a decongestant; an expectorant; a muscle relaxant; a further non-steroidal anti-inflammatory drug (hereinafter known as NSAID) other than 2-(4-isobutylphenyl)propionic acid or its salts; and combinations thereof.
  • NSAID non-steroidal anti-inflammatory drug
  • Suitable antihistamines which are preferably non-sedating include acrivastine, astemizole, azatadine, azelastine, bromodiphenhydramine, brompheniramine, carbinoxamine, cetirizine, chloropheniramine, cyproheptadine , dexbromopheniramine, dexchlorpheniramine, diphenhydramine, ebastine, ketoifen, lodoxamide, loratidine, levelcubastine, equitazine, oxatomide, phenindamine, phenyltoloxamine, pyridamine, setastine, tazifylline, warmthlastine, terfenadine, tripelennamine or tripolidine.
  • Suitable cough suppressants include caramiphen, codeine or dextromethorphan.
  • Suitable decongestants include pseudeoephedrine, phenylpropanolamine and phenylephrine.
  • Suitable expectorants include guaifensin, potassium citrate, potassium guaiacolsulphonate, potassium sulphate and terpin hydrate.
  • NSAIDs can be classified chemically as derivatives of arylcarboxylic acids, including salicylic and anthranilic acid derivatives; arylalkanoic acids, including arylacetic, arylpropionic, heteroarylacetic, indoleacetic and indenacetic acids; and enolic acids, including pyrazolidinediones and oxicams .
  • NSAID when used herein includes, but is not restricted to, the following compounds and pharmaceutically acceptable salts thereof.
  • Arylcarboxylic acids salicylic acid, acetylsalicylic acid, diflunisal, chlorine magnesium trisalicylate, salicylate, benorylate, flufenamic acid, mefenamic acid, meclofenamic acid, niflumic acid;
  • Arylalkanoic acids diclofenac, fenclofenac, alcofenac, fentaizac, flurbiprofen, ketoprofen, naproxen, fenorprofen, fenburfen, suprofen, indiprofen, tiaprofen acid, benoxaprofen, pirprofen tolmetin, zomepirac, clopinac, indomethacin, sulindac;
  • Enolic acids phenylbutazone, oxyphenbutazone, azapropazone, feprazone, piroxicam, isoxicam, sudoxicam.
  • compositions according to the present invention may be packaged in any conventional means to protect them from moisture, such as aluminium sachets for powder compositions, or aluminium foil strips for tablet compositions. Tablet compositions may be coated with conventional film or sugar coatings.
  • the present invention further comprises a method of making the powder or tablet .
  • compositions described herein comprising blending in a single step a water soluble pharmaceutically acceptable salt of 2- (4- isobutylphenyl)propionic acid, as either enantiomer or any mixture thereof, having a crystal size from 180 microns to 800 microns with a pharmaceutically acceptable couple comprising at least one acid component and at least one carbonate component to produce a uniform intimately mixed composition; followed by the optional step of adding after the blending step any optional ingredients; followed by the further optional step of compressing the composition in a tablet die to produce tablets.
  • the 2-(4- isobutylphenyl)propionic acid salt and/or the two components of the couple may be pregranulated by any convenient method such as wetting. Initial contact between the two components of the couple may produce some slight effervescence in the mixture, which is useful in the production of tablets as it can improve the compressibility of the resultant composition.
  • the blended composition thus produced can be optionally granulated (for example by a method such as fluidised bed granulation) to produce a more even particle size, reduce agglomeration and make tabletting the composition easier if tablets are being produced.
  • a further aspect of the invention comprises use of the compositions disclosed herein in the treatment of pain and fever, the compositions comprising a therapeutically effective amount of a water soluble pharmaceutically acceptable salt of 2- (4- isobutylphenyl)propionic acid, as either enantiomer separately or any mixture thereof.
  • compositions of the invention are generally prepared in unit dosage form.
  • the unit dosage of the 2- (4-isobutylphenyl)propionic acid salt is from about 50 mg to about 2000 mg.
  • the amount of the 2-(4-isobutylphenyl)propionic acid salt is calculated to provide doses equivalent by weight to doses of, for example, 50 mg, 100 mg, 200 mg, 400 mg, 800 mg or 1600 mg (preferably 200 mg or 400 mg) of racemic 2- (4-isobutylphenyl)propionic acid.
  • the quantity of the 2- (4-isobutylphenyl)propionic acid salt in each dose may be substantially reduced to have equivalent effect to the above mentioned doses of the racemic acid.
  • ibuprofen (900 kg) [produced by any convenient method], and flakes of B.P. grade sodium hydroxide (185.5 kg) were dissolved in industrial methylated spirit 600 B.P. (3,078 kg) to give coarse flaky crystals of sodium ibuprofen dihydrate (854 kg) .
  • the coarse sodium ibuprofen dihydrate crystals were separated from the reaction mixture, dried and used without further purification as an ingredient in the following composition.
  • the crystal shape of sodium ibuprofen was determined by microscopic image analysis to be flat, planar flakes, crystal size being measured in the plane which appears in the microscopic screen, with the crystals lying flat and 95% of the crystals were found to have a size in the range of 180 microns to 630 microns.
  • Example 2 These ingredients were combined in the above ratios using the method described in Example 1 to prepare solid tablets.
  • the sodium ibuprofen dihydrate was produced as described in Example 1 and had a similar crystal size to the sodium ibuprofen dihydrate used in Example 1, measured in a similar manner.
  • Example 2 These ingredients were combined in the above ratios using the method described in Example 1 to prepare solid tablets.
  • the sodium ibuprofen dihydrate was produced as described in Example 1 and had a similar crystal size to the sodium ibuprofen dihydrate used in Example 1, measured in a similar manner.
  • Example 2 These ingredients were combined in the above ratios using the method described in Example 1 to prepare solid tablets.
  • the sodium ibuprofen dihydrate was produced as described in Example 1 and had a similar crystal size to the sodium ibuprofen dihydrate used in Example 1, measured in a similar manner.
  • Example 2 Total These ingredients were combined in the above ratios using the method described in Example 1 to prepare solid tablets.
  • the sodium ibuprofen dihydrate was produced as described in Example 1 and had a similar crystal size to the sodium ibuprofen dihydrate used in Example 1, measured in a similar manner.
  • Pseudoephedrine hydr ⁇ chloride Anhydrous citric acid Sodium bicarbonate Sodium lauryl sulphate
  • Example 2 These ingredients were combined in the above ratios using the method described in Example 1 to prepare solid tablets.
  • the sodium ibuprofen dihydrate was produced as described in Example 1 and had a similar crystal size to the sodium ibuprofen dihydrate used in Example 1, measured in a similar manner.
  • the ibuprofen salt was present at a level equivalent to 100 mg (128 mg) , 200 mg (256 mg) and 400 mg (512 mg) of ibuprofen (mass of salt in parentheses) .
  • Example 7
  • Example 7 The S(-)sodium ibuprofen dihydrate was produced in a similar manner to that described in Example 1 from pharmaceutical grade S(+) -ibuprofen and had a similar crystal size to the racemic sodium ibuprofen dihydrate used in Example 1, measured in a similar manner.
  • Each tablet of Example 7 comprised 256 mg of S(-)sodium ibuprofen dihydrate (equivalent to 200 mg of S(+) -ibuprofen) .
  • the sodium lauryl sulphate ingredient was omitted from each of Examples 1 to 7 respectively, and granules were prepared as described in Example 1 prior to the tablet compression step, to give respective effervescent powder compositions Examples 8 to 14.

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Abstract

Composition pharmaceutique sous forme de poudre entrant en effervescence lorsqu'elle est ajoutée à de l'eau pour former une solution aqueuse transparente à administration orale. La composition renferme: un sel pharmaceutiquement acceptable soluble dans l'eau d'un acide 2-(4-isobutylphenyl)propionique, en tant que l'un des deux énantiomères, séparément ou sous forme de mélange, en combinaison intime avec un couple pharmaceutiquement acceptable comprenant au moins un composant acide et un composant carbonate, ce couple produisant du dioxyde de carbone en présence d'eau; dans cette composition, une proportion de l'ibuprofène égale à 95 % ou plus présente une dimension des cristaux comprise entre 180 et 800 microns et son composant carbonate est présent sous une quantité comprise entre deux et six fois la quantité du composant acide, de telle sorte que le pH de la solution aqueuse élaborée avec 1 gramme de la composition de 100 ml est supérieure à 5,0. L'invention porte sur une telle composition de comprimés renfermant en outre un agent tensioactif pharmaceutiquement acceptable, tel que du sulphate de lauryle de sodium et, facultativement, un lubrifiant. Cette composition effervescente peut en outre contenir des ingrédients pharmacologiquement actifs employés couramment pour soigner les rhumes et les refroidissements.
PCT/EP1993/003207 1992-11-16 1993-11-16 Compositions effervescentes de sel d'ibuprofene Ceased WO1994010994A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU54660/94A AU5466094A (en) 1992-11-16 1993-11-16 Ibuprofen salt effervescent compositions

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB9224021.7 1992-11-16
GB929224021A GB9224021D0 (en) 1992-11-16 1992-11-16 Effervescent compositions

Publications (1)

Publication Number Publication Date
WO1994010994A1 true WO1994010994A1 (fr) 1994-05-26

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GB (1) GB9224021D0 (fr)
WO (1) WO1994010994A1 (fr)
ZA (1) ZA938539B (fr)

Cited By (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1995034284A1 (fr) * 1994-06-15 1995-12-21 Gerhard Gergely Preparation pharmaceutique comportant un principe actif hydrophobe et un systeme effervescent, et procede de fabrication de ladite preparation
EP0769294A1 (fr) * 1995-10-17 1997-04-23 RECKITT & COLMAN PRODUCTS LIMITED Solutions aqueuses masquant le goût contenant du menthol
EP0748628A3 (fr) * 1995-06-13 1997-04-23 American Home Prod Compositions orales contenant de l'S(+)-étodolac
EP0753296A3 (fr) * 1995-06-13 1997-04-23 American Home Prod Compositions orales, contenant de l'S(+)-ibuprofène
WO1999049843A1 (fr) * 1998-03-31 1999-10-07 Asta Medica Aktiengesellschaft Formulations solides et a decomposition rapide contenant de la cetirizine
US6284271B1 (en) 1997-07-01 2001-09-04 Astrazeneca Ab Multiple unit effervescent dosage form
WO2002083105A3 (fr) * 2001-04-10 2003-04-10 Zagros Pharma Inc Composition pour une meilleure absorption d'anti-inflammatoires non steroidiens
WO2004066978A1 (fr) * 2003-01-23 2004-08-12 The Procter & Gamble Company Compositions pharmaceutiques en poudre
WO2004069132A3 (fr) * 2003-02-06 2004-10-28 Gebro Pharma Gmbh Preparations pharmaceutiques et leur procede de production
JP2006505558A (ja) * 2002-10-14 2006-02-16 エフ．ホフマン−ラ　ロシュ　アーゲー イブプロフェンナトリウムの剤形
EP1800667A1 (fr) 2005-12-23 2007-06-27 Losan Pharma GmbH Granulate d'ibuprofen solubilisé rapidement
EP1814512A2 (fr) * 2004-08-31 2007-08-08 Aristocon Verwaltungs-GmbH Formes galeniques perorales pour obtenir un effet de retard apres la prise de medicament lors d'un repas
EP2559430A1 (fr) 2005-03-22 2013-02-20 Losan Pharma GmbH Ibuprofen solubilisé
US20140030326A1 (en) * 2011-05-18 2014-01-30 Mahmut Bilgic Effervescent formulations comprising dexketoprofen
EP2965746A1 (fr) 2014-07-10 2016-01-13 Santa Farma Ilaç Sanayi A.S. Composition pharmaceutique orale comprenant de l'ibuprofène, du dihydrate de sodium d'ibuprofène, de l'hydrochlorure de pseudoéphédrine et du maléate de chlorophéniramine
EP2054367B1 (fr) 2006-08-22 2017-03-22 SI Group, Inc. Procédé de préparation de sel de sodium d'ibuprofène à dimensions de particules différentes
US10471006B2 (en) * 2017-07-06 2019-11-12 Marenda Pharmaceuticals Llc Blend compositions for oral administration as a rapidly dissolving powder and/or suspension

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1992020334A1 (fr) * 1991-05-13 1992-11-26 The Boots Company Plc Composition pharmaceutique comprenant un sel d'ibuprofene

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1992020334A1 (fr) * 1991-05-13 1992-11-26 The Boots Company Plc Composition pharmaceutique comprenant un sel d'ibuprofene

Cited By (29)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CH686865A5 (de) * 1994-06-15 1996-07-31 Gergely Gerhard Pharmazeutische Zubereitung mit einem hydrophoben Wirkstoff und einem Brausesystem, sowie Verfahren zur Herstellung der Zubereitung.
US5834019A (en) * 1994-06-15 1998-11-10 Gerhard Gergely Pharmaceutical formulation containing a hydrophobic active substance and an effervescent system
WO1995034284A1 (fr) * 1994-06-15 1995-12-21 Gerhard Gergely Preparation pharmaceutique comportant un principe actif hydrophobe et un systeme effervescent, et procede de fabrication de ladite preparation
EP0748628A3 (fr) * 1995-06-13 1997-04-23 American Home Prod Compositions orales contenant de l'S(+)-étodolac
EP0753296A3 (fr) * 1995-06-13 1997-04-23 American Home Prod Compositions orales, contenant de l'S(+)-ibuprofène
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GB9224021D0 (en) 1993-01-06
ZA938539B (en) 1994-05-23

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