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WO1997021424A1 - Gomme a macher contenant de la ranitidine - Google Patents

Gomme a macher contenant de la ranitidine Download PDF

Info

Publication number
WO1997021424A1
WO1997021424A1 PCT/EP1996/005468 EP9605468W WO9721424A1 WO 1997021424 A1 WO1997021424 A1 WO 1997021424A1 EP 9605468 W EP9605468 W EP 9605468W WO 9721424 A1 WO9721424 A1 WO 9721424A1
Authority
WO
WIPO (PCT)
Prior art keywords
chewing gum
ranitidine
bulking agent
base
chewing
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/EP1996/005468
Other languages
English (en)
Inventor
Frédérique Annie Nathalie BOUAFFRE
Jean-Pierre Lafon
Jean Laurent André PERRIN
Xavier Marc SALANÇON
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.)
Laboratoire Glaxo Wellcome SA
Original Assignee
Laboratoire Glaxo Wellcome SA
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 Laboratoire Glaxo Wellcome SA filed Critical Laboratoire Glaxo Wellcome SA
Priority to AU11914/97A priority Critical patent/AU1191497A/en
Publication of WO1997021424A1 publication Critical patent/WO1997021424A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

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
    • A61K9/0012—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
    • A61K9/0058—Chewing gums

Definitions

  • the present invention relates to improvements in the formulation of the histamine H2-receptor antagonist ranitidme, particularly for oral administration
  • Oral administration constitutes a preferred route for administering ranitidme Ranitidme, however, in common with many drug substances, has an inherently bitter taste, and this constitutes a disadvantage with certain types of oral preparation
  • the problems resulting from the bitter taste of ranitidme are particularly acute in chewable formulations
  • compositions for the oral, systemic delivery of H 2 antagonists have not previously been described, although topical chewing gum compositions for the treatment of gingivitis or pe ⁇ odontitis containing H 2 - receptor antagonists are described generally in US5294433
  • compositions comprising 0 1 % to 10% of an H 2 antagonist and a chewing gum carrier (comprising a gum base, a flavouring agent and a sweetening agent) are disclosed
  • a chewing gum carrier comprising 0 1 % to 10% of an H 2 antagonist and a chewing gum carrier (comprising a gum base, a flavouring agent and a sweetening agent) are disclosed
  • a chewing gum carrier comprising 0 1 % to 10% of an H 2 antagonist and a chewing gum carrier (comprising a gum base, a flavouring agent and a sweetening agent) are disclosed
  • chewing gum carrier comprising 0 1 % to 10% of an H 2 antagonist and a chewing gum carrier (comprising a gum base
  • Chewable formulations are a particularly convenient form of oral presentation for patients who prefer not to take swallowable tablets, or find difficulty in swallowing them
  • a chewing gum formulation would be a particularly convenient way of administering ranitidme systemically, especially in the treatment of minor conditions such as acid indigestion and heartburn
  • a further problem to be overcome if one is to arhve at a sufficiently stable ranitidine chewing gum is due to ranitidine's tendency to degrade in the presence of moisture.
  • Conventional sugar-free chewing gum compositions contain large amounts of hygroscopic sugar alcohols which result in the gum having a high moisture content, around 3 to 5%, which is further increased by moisture uptake on storage.
  • Substantially anhydrous chewing gum compositions have been described, for example US3262784 relates to dry, granular chewing gum compositions comprising a chewing gum base and sugar granules which produces chewing gum granules which can be compressed into shape.
  • US4961935 describes anhydrous chewing gum compositions comp ⁇ sing a gum base, a non-hygroscopic bulking agent, such as an isomalt, a softening agent and a sweetening agent.
  • the chewing gum is prepared by heating the gum base at 60 to 120°C until molten, mixing with the other ingredients whilst still in the molten state and then forming the gum into shapes.
  • the chewing gum ingredients are exposed to a period of working at elevated temperature which could result in degradation of heat-sensitive components. Since it is known that the degradation of ranitidine is accelerated by heat, it would be advantageous to avoid excess exposure to heat during the formulation process.
  • ranitidine chewing gum composition which avoids the problems of exposure to moisture and heat, thus ensuring the stability of ranitidine, and where the bitter taste of ranitidine is effectively masked and which provides a rapid and effective release of ranitidine resulting in advantageous bioavailability.
  • the present invention provides a chewing gum composition
  • a chewing gum composition comprising a gum base, a non-hygroscopic bulking agent, a flavouring, a high-intensity sweetener and ranitidine, or a physiologically acceptable salt thereof.
  • Ranitidme may be employed in the compositions according to the invention in the form of either its free base or a physiologically acceptable salt
  • Such salts include salts with inorganic or organic acids such as the hydrochloride, hydrobromide, sulphate, acetate, maleate, succinate, citrate, tartrate, fumarate and ascorbate salts
  • a particularly preferred salt of ranitidme is the hydrochloride
  • the gum base may be selected from any suitable water-insoluble gum base known in the art and includes those gum bases utilised for chewing gums and bubble gums
  • the gum base may comp ⁇ se a polymer, such as an elastomeric polymer, resins, waxes, glycerol esters of edible fatty acids plasticizers, mineral adjuvants such as talc and other conventional additives such as antioxidants
  • a particularly suitable gum base is the commercially available "DELTA T"
  • the gum base suitably comprises 15 to 20% of the total composition, for example around 18%
  • the ratio of gum base to non-hygroscopic bulking agent is suitably in the range 1 3 to 1 5, for example 1 4
  • the non-hygroscopic bulking agent is preferably an isomalt, i e a mixture such as a racemic mixture of 1-O-alpha-D-glucopyranosyl-D-mann ⁇ tol and 6-O-alpha- D-glucopyranosyl-D-glucitol, for example the commercially available "PALATINIT” or "PALATINOL”
  • the non-hygroscopic bulking agent suitably comprises 60 to 80% of the total composition, for example around 70%
  • flavouring in the compositions according to the invention ts a strong flavouring such as fruit flavours and natural or synthetic mint or peppermint flavours Strong mint or peppermint flavourings are preferred
  • the chewing gum composition also optionally contains an acidifying agent such as sodium citrate
  • the high intensity sweetener includes saccharine and cyclamic acid and their various salts or, more preferably, dipeptide sweeteners such as aspartame
  • the chewing gum composition may also include a lubricant such as magnesium stearate
  • a lubricant such as magnesium stearate
  • the present invention provides a chewing gum composition comprising a gum base, a non-hygroscopic bulking agent, e.g an isomalt, a flavouring, e.g. a strong mint or peppermint flavouring, a high intensity sweetener, e.g. aspartame, a lubricant, e.g. magnesium stearate and ranitidine, or a physiologically acceptable salt thereof, e.g. the hydrochloride salt.
  • chewing gum compositions according to the invention are for the oral, systemic delivery of ranitidine and not topical delivery It will also be appreciated that the instant chewing gum compositions are essentially sugarless.
  • the chewing gum compositions according to the instant invention are preferably in the form of chewing gum tablets.
  • ranitidine preferably in the form of a physiologically acceptable salt, particularly ranitidine hydrochloride, in the composition according to the invention is preferably in the range of 10 to 800mg per dosage unit (for example per chewing gum tablet), e.g. 20 to 600mg, more preferably 25 to 300mg, such as 25, 75, 125 or 150mg, expressed as the weight of free base.
  • the unit dose (for example contained in one chewing gum tablet according to the invention) may be administered up to, for example, 6 times a day depending upon the unit dose used, the nature and seventy of the conditions being treated, and the age and weight of the patient
  • gastric acidity such as, for example, acid indigestion, over-indulgence of food or drink, acid stomach, sour stomach, waterbrash/regurgitation, heartburn, such as episodic heartburn, nocturnal heartburn, and meal-induced heartburn, gastritis and dyspepsia
  • lower and more frequent doses of ranitidine may be used, for example doses in the range of 10-150mg, e.g 25-75mg ranitidine expressed as the weight of free base, administered up to 6 times a day as and when required
  • more serious conditions such as duodenal and gastric ulceration, reflux oesophagitis and Zollinger-Ellison syndrome, higher and less frequent
  • the chewing gum compositions according to the instant invention may be prepared by heating the gum base until molten according to conventional procedures, for example at around 70°C, allowing the gum base to cool, yet maintaining it in its molten state, for example at around 40-45°C, adding the preheated bulking agent, for example portion wise, e.g. 60% of the total amount, and at a temperature of, for example 30-35°C, and blending and cooling the mixture, for example at about 30°C.
  • the remaining bulking agent is added, for example the remaining 40%, and the mixture is further blended and cooled, for example at around 25°C, at which stage a free flowing powder is produced.
  • the step of cooling and blending the gum base/bulking agent mixture to produce a free flowing powder is novel and constitutes a further aspect of the invention.
  • the free flowing powder is then blended with the ranitidine and other ingredients according to conventional anhydrous blending procedures.
  • the gum base/bulking agent mixture is dry blended or dry granulated with ranitidine followed by the remaining ingredients and then the mixture is compressed into tablet shapes.
  • the gum base used is DELTA T, available from Cafosa Gum SA, Barcelona, Spain, and the isomalt is PALATINIT.
  • DELTA T and PALATINIT are tradenames.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Zoology (AREA)
  • Nutrition Science (AREA)
  • Physiology (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Medicinal Preparation (AREA)

Abstract

La présente invention se rapporte à une composition de gomme à mâcher comprenant une gomme de base, un ingrédient de charge non hygroscopique, un agent d'aromatisation, un édulcorant très puissant, ainsi que de la ranitidine, ou un sel de celle-ci, acceptable sur le plan physiologique. On décrit également un procédé de préparation de cette composition.
PCT/EP1996/005468 1995-12-09 1996-12-06 Gomme a macher contenant de la ranitidine Ceased WO1997021424A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU11914/97A AU1191497A (en) 1995-12-09 1996-12-06 Chewing gum containing ranitidine

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GBGB9525240.9A GB9525240D0 (en) 1995-12-09 1995-12-09 Ranitidine compositions
GB9525240.9 1995-12-09

Publications (1)

Publication Number Publication Date
WO1997021424A1 true WO1997021424A1 (fr) 1997-06-19

Family

ID=10785216

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP1996/005468 Ceased WO1997021424A1 (fr) 1995-12-09 1996-12-06 Gomme a macher contenant de la ranitidine

Country Status (3)

Country Link
AU (1) AU1191497A (fr)
GB (1) GB9525240D0 (fr)
WO (1) WO1997021424A1 (fr)

Cited By (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002051259A1 (fr) * 2000-12-22 2002-07-04 Wm. Wrigley Jr. Company Produits a macher enrobes contenant divers antiacides
WO2002078459A1 (fr) * 2001-03-29 2002-10-10 Societe Des Produits Nestles S.A. Tablette renfermant du chewing gum
US6949264B1 (en) 1996-11-27 2005-09-27 Wm. Wrigley Jr. Company Nutraceuticals or nutritional supplements and method of making
US7078052B2 (en) 1999-04-06 2006-07-18 Wm. Wrigley Jr. Company Pharmaceutical chewing gum formulations
US7115288B2 (en) 2000-06-09 2006-10-03 Wm. Wrigley Jr. Company Method for making coated chewing gum products with a coating including an aldehyde flavor and a dipeptide sweetener
US7163705B2 (en) 1998-12-15 2007-01-16 Wm. Wrigley Jr. Company Coated chewing gum product and method of making
US7208186B2 (en) 2001-09-18 2007-04-24 Spi Pharma, Inc. Chewing gum formulation and method of making the same
CN100366146C (zh) * 2002-03-08 2008-02-06 丘福.加托股份有限公司 一种动物咀嚼玩具
WO2009007768A1 (fr) * 2007-07-06 2009-01-15 Gumlink A/S Comprimé comprenant un polyol
WO2011080500A3 (fr) * 2009-12-29 2011-11-10 Orexo Ab Nouvelle forme pharmaceutique destinée au traitement de troubles liés à l'acide gastrique
WO2011080502A3 (fr) * 2009-12-29 2011-11-10 Orexo Ab Nouvelle forme pharmaceutique destinée au traitement de troubles liés à l'acide gastrique
WO2011080501A3 (fr) * 2009-12-29 2011-11-10 Orexo Ab Nouvelle forme pharmaceutique destinée au traitement de troubles liés à l'acide gastrique
US8137477B2 (en) 2005-03-22 2012-03-20 Gumlink A/S Method of cleaning a surface attached with at least one chewing gum lump

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2808160A1 (de) * 1978-02-25 1979-08-30 Nordstroem Rabbe Neuartige tablette und das verfahren zur herstellung eines solchen presslings
EP0151344A2 (fr) * 1984-01-31 1985-08-14 Warner-Lambert Company Composition pour gomme à mâcher, procédé de préparation d'un bâton de gomme à mâcher à partir de celle-ci et bâton de gomme à mâcher
WO1988008671A1 (fr) * 1987-05-04 1988-11-17 Wm. Wrigley Jr. Company Chewing-gum sans sucre ameliore a enrobage dur
CA2068366A1 (fr) * 1991-05-10 1992-11-11 Angelo M. Morella Composition de microcapsule et procede
US5294433A (en) * 1992-04-15 1994-03-15 The Procter & Gamble Company Use of H-2 antagonists for treatment of gingivitis

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2808160A1 (de) * 1978-02-25 1979-08-30 Nordstroem Rabbe Neuartige tablette und das verfahren zur herstellung eines solchen presslings
EP0151344A2 (fr) * 1984-01-31 1985-08-14 Warner-Lambert Company Composition pour gomme à mâcher, procédé de préparation d'un bâton de gomme à mâcher à partir de celle-ci et bâton de gomme à mâcher
WO1988008671A1 (fr) * 1987-05-04 1988-11-17 Wm. Wrigley Jr. Company Chewing-gum sans sucre ameliore a enrobage dur
CA2068366A1 (fr) * 1991-05-10 1992-11-11 Angelo M. Morella Composition de microcapsule et procede
US5294433A (en) * 1992-04-15 1994-03-15 The Procter & Gamble Company Use of H-2 antagonists for treatment of gingivitis

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
DATABASE WPI Week 6800, Derwent World Patents Index; AN 66-15950f, XP002028473 *

Cited By (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6949264B1 (en) 1996-11-27 2005-09-27 Wm. Wrigley Jr. Company Nutraceuticals or nutritional supplements and method of making
US7163705B2 (en) 1998-12-15 2007-01-16 Wm. Wrigley Jr. Company Coated chewing gum product and method of making
US7078052B2 (en) 1999-04-06 2006-07-18 Wm. Wrigley Jr. Company Pharmaceutical chewing gum formulations
US7115288B2 (en) 2000-06-09 2006-10-03 Wm. Wrigley Jr. Company Method for making coated chewing gum products with a coating including an aldehyde flavor and a dipeptide sweetener
WO2002051259A1 (fr) * 2000-12-22 2002-07-04 Wm. Wrigley Jr. Company Produits a macher enrobes contenant divers antiacides
WO2002078459A1 (fr) * 2001-03-29 2002-10-10 Societe Des Produits Nestles S.A. Tablette renfermant du chewing gum
US7208186B2 (en) 2001-09-18 2007-04-24 Spi Pharma, Inc. Chewing gum formulation and method of making the same
CN100366146C (zh) * 2002-03-08 2008-02-06 丘福.加托股份有限公司 一种动物咀嚼玩具
US8137477B2 (en) 2005-03-22 2012-03-20 Gumlink A/S Method of cleaning a surface attached with at least one chewing gum lump
WO2009007768A1 (fr) * 2007-07-06 2009-01-15 Gumlink A/S Comprimé comprenant un polyol
WO2011080500A3 (fr) * 2009-12-29 2011-11-10 Orexo Ab Nouvelle forme pharmaceutique destinée au traitement de troubles liés à l'acide gastrique
WO2011080502A3 (fr) * 2009-12-29 2011-11-10 Orexo Ab Nouvelle forme pharmaceutique destinée au traitement de troubles liés à l'acide gastrique
WO2011080501A3 (fr) * 2009-12-29 2011-11-10 Orexo Ab Nouvelle forme pharmaceutique destinée au traitement de troubles liés à l'acide gastrique

Also Published As

Publication number Publication date
AU1191497A (en) 1997-07-03
GB9525240D0 (en) 1996-02-07

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