WO2008090038A1 - Composition pharmaceutique pulvérulente comprenant de l'ibuprofène - Google Patents

Composition pharmaceutique pulvérulente comprenant de l'ibuprofène Download PDF

Info

Publication number
WO2008090038A1
WO2008090038A1 PCT/EP2008/050288 EP2008050288W WO2008090038A1 WO 2008090038 A1 WO2008090038 A1 WO 2008090038A1 EP 2008050288 W EP2008050288 W EP 2008050288W WO 2008090038 A1 WO2008090038 A1 WO 2008090038A1
Authority
WO
WIPO (PCT)
Prior art keywords
pharmaceutical composition
polyalcohol
weight
ibuprofen
composition according
Prior art date
Application number
PCT/EP2008/050288
Other languages
English (en)
Inventor
Carlos Fernandez Navarro
Julian Agut Sanchez
Gabriel Espelleta Gil
Miquel Junca Riuro
Josep Junca Busquets
Ferran Junca Riuro
Jaime MELENDO BAÑOS
Original Assignee
Masterfarm, S.L.
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 Masterfarm, S.L. filed Critical Masterfarm, S.L.
Publication of WO2008090038A1 publication Critical patent/WO2008090038A1/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
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid 
    • 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
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
    • A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
    • A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
    • A61K47/183—Amino acids, e.g. glycine, EDTA or aspartame
    • 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
    • A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
    • A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches

Definitions

  • the present invention refers to a pharmaceutical composition in powder form which comprises ibuprofen.
  • the invention also refers to a process for the preparation of this composition, which has analgesic, antipyretic and anti-inflammatory activity, is orally administrable after dissolution in water and has a final flavour that is pleasant to the consumer's palate.
  • Ibuprofen is an anti-inflammatory agent with analgesic and antipyretic activity that is widely used in multiple medical treatments. Due to its bad taste (intensely pungent), the majority of ibuprofen-based presentations are in the form of tablets or capsules; the disadvantage is that, since the pharmaceutical form must first break up in the stomach and the active principle must then be dissolved in order to be absorbed by the body, the effects take about thirty minutes to become evident, which is a problem in many types of pains that require rapid action.
  • soluble ibuprofen salts with basic amino acids, mainly lysine salt (ibuprofen lysinate) and ibuprofen arginine. Both salts are soluble and make it possible to obtain a pharmaceutical form in powder form that is easily dissolved in water and allows for administration in liquid form. This leads to a greater speed of action, which, as already discussed, is very useful in certain types of pain, such as toothaches.
  • flavour which does not allow for ingestion of the product to be pleasant; moreover, since the ibuprofen is in solution, the unpleasant pungent flavour is even stronger. And even when the bad taste is somewhat masked with some type of aroma, the final flavour is always unpleasant and leaves a tingling sensation in the throat that persists for quite some time.
  • Cyclodextrins are obtained from the enzymatic hydrolysis of starch and, depending on the enzyme used, the Alpha (6 glucose units), Beta (7 glucose units) or Gamma (8 glucose units) forms are obtained, which differ in the diameter of the circle and, therefore, may form complexes with products having a higher or lower molecular weight.
  • beta-cyclodextrin which is composed of 7 glucose units cyclically bonded to form a ring. Its molecular weight is 1 135 and its structure is shown in formula I.
  • R' and R" groups are hydrogens in the case of beta-cyclodextrin; thus, it is easy to understand the existence of complexes of different products via the formation of hydrogen bridges. When these complexes are formed, the functional group responsible for a product's bad taste may become "blocked" by the new bonds formed.
  • Manitol and sorbitol may also be used as plasticisers for the gelatin used in soft- gelatin capsules adapted to contain active principles; and also as crystallisation inhibitors in sugar syrups.
  • manitol is also used as a lyophilisation excipient because it favours the sublimation process.
  • the present invention proposes a pharmaceutical composition with a soluble ibuprofen salt that surprisingly has a pleasant flavour, as much or more so than compositions made of ibuprofen salts and cyclodextrins, and the manufacturing cost whereof allows for subsequent marketing at a competitive price.
  • the object of the present invention is a pulverulent pharmaceutical composition
  • a pulverulent pharmaceutical composition comprising ibuprofen and at least one pharmaceutical-quality excipient, suitable to be administered in aqueous solution and having a pleasant flavour.
  • the pulverulent pharmaceutical composition is characterised in that, as an active principle, it comprises at least one soluble ibuprofen salt with basic amino acids associated with at least one polyalcohol, the molar relation between the soluble ibuprofen salt and the polyalcohol being between 1 :2 and 1 :12.
  • the pharmaceutical composition according to the invention is also characterised in that the molar relation between the soluble ibuprofen salt and the polyalcohol is between 1 :4 and 1 :8.
  • the soluble ibuprofen salt is independently selected from the group formed by ibuprofen lysinate and ibuprofen arginine or a mixture thereof.
  • the pulverulent pharmaceutical composition according to the invention is characterised in that the polyalcohol is independently selected from the group formed by manitol, sorbitol and maltitol, or a mixture thereof.
  • the polyalcohol is preferably manitol.
  • the composition comprises at least one pharmaceutical-quality excipient independently selected from the group - A -
  • the pharmaceutical composition according to the invention is characterised in that it comprises, with respect to the total weight thereof: - between 60% and 95% by weight of the association of soluble ibuprofen salt with basic amino acid and polyalcohol;
  • colloidal silicium dioxide - between 0.4% and 0.8% by weight of colloidal silicium dioxide
  • the pulverulent composition of the invention comprises between 60% and 95% by weight of soluble ibuprofen salt with a basic amino acid associated with manitol and/or sorbitol.
  • the pharmaceutical composition according to the invention is also characterised in that it comprises between 60% and 95% by weight, with respect to the total composition, of lysinate and/or ibuprofen arginine associated with manitol and/or sorbitol.
  • the pulverulent pharmaceutical composition according to the invention is in the form of single-dose sachets, the content being water-soluble for oral administration.
  • Another object of the present invention is a process for the preparation of a pulverulent pharmaceutical composition comprising ibuprofen and at least one pharmaceutical-quality excipient, which is suitable to be administered in aqueous solution and has a pleasant flavour, said process being characterised in that it comprises the following steps: a) Jointly sieving the soluble ibuprofen salt with a basic amino acid and the polyalcohol. b) Mixing and homogenizing both components. c) Sieving and mixing the dry mixture of soluble ibuprofen salt with a basic amino acid and the polyalcohol with the suitable pharmaceutical-quality excipients for administration in aqueous solution.
  • the process for the preparation of a pulverulent pharmaceutical composition according to the invention is characterised in that, following step b) and prior to step c), the following steps are performed:
  • the process for the preparation of a pulverulent pharmaceutical composition comprises a step wherein the manufactured composition is packed in single-dose sachets.
  • a pharmaceutical composition that comprises, as an active principle, at least one soluble ibuprofen salt with basic amino acids, such as lysine and arginine, the salt being associated with at least one carbohydrate with multiple hydroxyl groups, such as manitol, sorbitol, maltitol, glucose, galactose, etc.; and where the molar relation between said soluble ibuprofen salt and the carbohydrate with multiple hydroxyl groups is between 1 :2 and 1 :12.
  • Assay Selection of the carbohydrate with multiple hydroxyl groups and comparison of the final composition's organoleptic characteristics with those of compositions containing cyclodextrins.
  • assays were performed with the following products: glucose, fructose, sucrose, lactose, maltose, maltodextrin and polydextrose.
  • the assays were performed by mixing each of the products described above with soluble ibuprofen salts in molar relations between 2 to 1 and 12 to 1 (carbohydrate/soluble ibuprofen salt).
  • a mixture of beta-cyclodextrin with the soluble ibuprofen salts in a molar proportion of 1 to 1 was also prepared, also under dry and humid conditions.
  • the soluble ibuprofen salts that were assayed were the salts of the active principle with basic amino acids, namely: ibuprofen lysinate and ibuprofen arginine.
  • manitol and sorbitol are isomers and vary in the orientation of the hydroxyl group in carbon 2.
  • sorbitol is like glucose, but with the aldehyde group in carbon 1 reduced to alcohol, and in both cases the possibility of creating hydrogen bridge bonds is very high.
  • parallel galenic developments were initiated with both products in order to achieve the initial objective, which was to obtain a pharmaceutical form in powder form that could be distributed in single-dose sachets and administered by solution thereof in cold water, achieving a rapid solution of ibuprofen and a pleasant flavour to facilitate ingestion.
  • excipients for the pharmaceutical form are preferably, albeit not exclusively, used: aspartame, ammonium glycyrrhizinate, fruit essences, sodium citrate, colloidal silicium dioxide and sucrose.
  • these excipients may be totally or partially replaced with other suitable excipients to achieve the pharmaceutical form, since the main basis for the rapid solution and the good flavour resides in the combination of ibuprofen lysinate with the above-mentioned polyalcohols.
  • composition of this invention comprises the following components in the following weight percentages:
  • composition of the invention may be outlined as follows:
  • lysinate is used as the ibuprofen salt and manitol is the preferred polyalcohol, although the same process is valid for other soluble ibuprofen salts with basic amino acids (such as ibuprofen arginine) and sorbitol may also be used as the polyalcohol, leading to identical results.
  • soluble ibuprofen salts and mixtures of manitol and sorbitol or other polyalcohols may also be used.
  • composition of the invention may also be prepared by omitting steps 3, 4 and 5 of the process described above.
  • the resulting homogeneous product is packed in single-dose aluminum foil sachets for subsequent oral administration, following solution in water or another aqueous medium (for instance, fruit juices).
  • aqueous medium for instance, fruit juices

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Engineering & Computer Science (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

La présente invention concerne une composition pharmaceutique pulvérulente comprenant de l'ibuprofène et au moins un excipient de qualité pharmaceutique, pouvant être administrée en solution aqueuse et ayant une saveur plaisante. En tant que matière active, la composition comprend au moins un sel soluble d'ibuprofène avec des acides aminés basiques associés à au moins un polyalcool. La composition comprend les excipients pharmaceutiquement acceptables à formuler sous forme de poudre soluble et garantissant une bonne saveur et elle est obtenue par une séquence d'étapes qui comprennent le tamisage conjoint du sel soluble d'ibuprofène avec un acide aminé basique et le polyalcool, le mélangeage et l'homogénéisation des composants et le tamisage et le mélangeage du soluble sel soluble d'ibuprofène avec un acide aminé basique et le polyalcool avec les excipients de qualité pharmaceutiques appropriés pour une administration en solution aqueuse.
PCT/EP2008/050288 2007-01-22 2008-01-11 Composition pharmaceutique pulvérulente comprenant de l'ibuprofène WO2008090038A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
ESP200700175 2007-01-22
ES200700175A ES2303468B1 (es) 2007-01-22 2007-01-22 "una composicion farmaceutica pulverulenta que comprende ibuprofeno".

Publications (1)

Publication Number Publication Date
WO2008090038A1 true WO2008090038A1 (fr) 2008-07-31

Family

ID=39402567

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2008/050288 WO2008090038A1 (fr) 2007-01-22 2008-01-11 Composition pharmaceutique pulvérulente comprenant de l'ibuprofène

Country Status (2)

Country Link
ES (1) ES2303468B1 (fr)
WO (1) WO2008090038A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107233317A (zh) * 2017-05-25 2017-10-10 北京万鹏朗格医药科技有限公司 一种含精氨酸布洛芬的药物组合物及其制备方法

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2602141A1 (fr) * 1986-08-01 1988-02-05 Zambon Spa Composition pharmaceutique a activite analgesique contenant de l'ibuprofene comme principe actif
US4788220A (en) * 1987-07-08 1988-11-29 American Home Products Corporation (Del.) Pediatric ibuprofen compositions
EP0350701A2 (fr) * 1988-07-12 1990-01-17 FARMA RESA S.r.l. Compositions pharmaceutiques pour administration orale à activités analgésiques et anti-inflammatoire, possédant un goût excellent et étant dépourvues d'effets irritants sur les membranes muqueuses
EP0424028A2 (fr) * 1989-10-17 1991-04-24 Merck & Co. Inc. Acide S(+)-ibuprofène-L-amino et l'acide S(+)-ibuprofène-D-amino comme agents analgésiques puissants
BE1007194A3 (fr) * 1993-06-21 1995-04-18 Zambon Spa Composition pharmaceutique ayant une activite analgesique.
EP1452169A1 (fr) * 2001-12-04 2004-09-01 Farmalider, S.A. Compositions pharmaceutiques liquides de base aqueuse en forme de suspension destinnees a l'administration par voie orale d'ibuprofene

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
IT1209667B (it) * 1985-11-12 1989-08-30 Zambon Spa Composizione effeverscente adattivita' analgesica.
ES2171110B1 (es) * 2000-03-03 2003-06-16 Aplicaciones Farmacodinamicas Composicion farmaceutica a base de ibuprofeno y procedimiento para su preparacion.

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2602141A1 (fr) * 1986-08-01 1988-02-05 Zambon Spa Composition pharmaceutique a activite analgesique contenant de l'ibuprofene comme principe actif
US4788220A (en) * 1987-07-08 1988-11-29 American Home Products Corporation (Del.) Pediatric ibuprofen compositions
EP0350701A2 (fr) * 1988-07-12 1990-01-17 FARMA RESA S.r.l. Compositions pharmaceutiques pour administration orale à activités analgésiques et anti-inflammatoire, possédant un goût excellent et étant dépourvues d'effets irritants sur les membranes muqueuses
EP0424028A2 (fr) * 1989-10-17 1991-04-24 Merck & Co. Inc. Acide S(+)-ibuprofène-L-amino et l'acide S(+)-ibuprofène-D-amino comme agents analgésiques puissants
BE1007194A3 (fr) * 1993-06-21 1995-04-18 Zambon Spa Composition pharmaceutique ayant une activite analgesique.
EP1452169A1 (fr) * 2001-12-04 2004-09-01 Farmalider, S.A. Compositions pharmaceutiques liquides de base aqueuse en forme de suspension destinnees a l'administration par voie orale d'ibuprofene

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107233317A (zh) * 2017-05-25 2017-10-10 北京万鹏朗格医药科技有限公司 一种含精氨酸布洛芬的药物组合物及其制备方法
CN107233317B (zh) * 2017-05-25 2020-07-24 北京万鹏朗格医药科技有限公司 一种含精氨酸布洛芬的药物组合物及其制备方法

Also Published As

Publication number Publication date
ES2303468B1 (es) 2009-06-08
ES2303468A1 (es) 2008-08-01

Similar Documents

Publication Publication Date Title
KR101458772B1 (ko) 페닐에프린을 함유하는 약제학적 현탁액 및 이의 제조 방법
JPH0822818B2 (ja) 被覆組成物およびその製造法
CA2017360A1 (fr) Forme pharmaceutique poreuse et sa preparation
JP2002544241A (ja) 生体活性剤の改良された細胞取り込み
JP5653602B2 (ja) 高吸収性薬剤組成物およびその製造方法
US5597583A (en) Pharmaceutical composition
KR20040047930A (ko) 파라세타몰과 쓴맛 차단 성분을 포함하는 조성물
JPH09501421A (ja) 薬物／β−シクロデキストリン複合物を酸−塩基カップルと組み合わせて含有する医薬組成物
US20240315961A1 (en) Semi-solid chewable compositions and methods of making and using thereof
JP2007131561A (ja) 経口固形製剤及びその製造法
JP2001106639A (ja) 経口用組成物
EP0839528B1 (fr) Compositions solubles dans la bouche contenant de la N-acetyl-cysteine et de la cyclodextrine
WO2008090038A1 (fr) Composition pharmaceutique pulvérulente comprenant de l'ibuprofène
EP1603550B1 (fr) Composition pharmaceutique contenant de l'acide 5-methyl-2-2'-(chloro-6'-fluoroanilino)phenylacetique
FR2649611A1 (fr) Procede de preparation galenique d'une composition therapeutique notamment a base d'aspirine
JPH0827033A (ja) エリスリトール含有固形剤
KR20060051486A (ko) 의약적 냉각 에멀젼
JP5977672B2 (ja) イブプロフェンリシナートの経口投与用の懸濁液
JP7263151B2 (ja) 経口組成物
US20040013693A1 (en) Liquid pharmaceutical composition
EP2253329B1 (fr) Suspension orale d'Ibuprofène lysinate.
KR100415857B1 (ko) 약물의 고미가 차폐된 경구투여용 조성물 및 이의 제조방법
RU2166937C1 (ru) Лекарственное средство на основе парацетамола
JPS63215640A (ja) 易吸収性抗炎症剤及びその製造方法
JPH0256416A (ja) 苦味を抑えた顆粒剤

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 08701432

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 08701432

Country of ref document: EP

Kind code of ref document: A1