WO1997021424A1 - Chewing gum containing ranitidine - Google Patents

Chewing gum containing ranitidine Download PDF

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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
Application number
PCT/EP1996/005468
Other languages
French (fr)
Inventor
Frédérique Annie Nathalie BOUAFFRE
Jean-Pierre Lafon
Jean Laurent André PERRIN
Xavier Marc SALANÇON
Original Assignee
Laboratoire Glaxo Wellcome
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 filed Critical Laboratoire Glaxo Wellcome
Priority to AU11914/97A priority Critical patent/AU1191497A/en
Publication of WO1997021424A1 publication Critical patent/WO1997021424A1/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
    • A61K9/0012—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.

Abstract

The present invention provides 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 and a process for its preparation.

Description

CHEWING GUM CONTAINING RANITIDINE.
The present invention relates to improvements in the formulation of the histamine H2-receptor antagonist ranitidme, particularly for oral administration
Ranitidme, N-[2-[[[5-(dιmethylamιno)methyl-2-furanyl]methyl]thιo]ethyl]-N'- methyl-2-nιtro-1 ,1-ethenedιamιne, and its physiologically acceptable salts are described and claimed in British Patent Specification No 1565966, and a particular crystalline form of ranitidme hydrochloride is described and claimed in British Patent Specification No 2084580 In both these specifications there is reference to formulations for oral administration, which may take the form of for example tablets, capsules, granules, powders solutions, syrups, suspensions or tablets or lozenges for buccal 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
Chewing gum compositions for the oral, systemic delivery of H2 antagonists have not previously been described, although topical chewing gum compositions for the treatment of gingivitis or peπodontitis containing H2- receptor antagonists are described generally in US5294433 Thus compositions comprising 0 1 % to 10% of an H2 antagonist and a chewing gum carrier (comprising a gum base, a flavouring agent and a sweetening agent) are disclosed There is no further teaching as to the nature of the chewing gum carrier, however, and chewing gum compositions containing ranitidme are not specifically disclosed
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 However since chewing gums remain in the mouth for an extended period, such a formulation presents particular difficulties if the taste of ranitidme is to be effectively masked 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.
An additional problem with conventional chewing gums lies in the method used to prepare them. This involves mixing a heated chewing gum base with an aqueous solution of the sugar alcohol.
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 compπsing 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.
Thus, according to the method of US4961935, 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.
A ranitidine chewing gum composition has now been discovered 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.
Thus, the present invention provides 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 Thus, for example, the gum base may compπse 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-mannιtol 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%
The 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 acidifiant 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 Thus, in a preferred aspect, 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.
It will be appreciated that the 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.
The amount of 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 Thus, for example, in the treatment of minor conditions where there is an advantage in lowering 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 For more serious conditions such as duodenal and gastric ulceration, reflux oesophagitis and Zollinger-Ellison syndrome, higher and less frequent doses of ranitidine will be employed, for example 75-600mg, e g 150mg unit doses administered one to four, preferably once or twice, daily
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. Thus, for example 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 following table illustrates non-limiting examples of the pharmaceutical compositions according to the invention.
In the following examples 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.
Ingredient Example 1 Example 2 Example 3 Example 4 mg/tablet mg/tablet mg/tablet mg/tablet
Ranitidine HCl 28.0 84.0 84.0 168.0
Gum Base 534 534 534 575
Isomalt 2100 2136 2136 2140
Peppermint Flavour 150 150 150 200
Sodium Citrate - - 30 30
Aspartame 10 22 22 25
Magnesium Stearate 40 44 44 60

Claims

1. A chewing gum comprising a gum base, a non-hygroscopic bulking agent, a flavouring, a high-intensity sweetener and ranitidine, or a physiologically acceptable salt thereof.
2. A chewing gum according to claim 1 wherein the gum base comprises 15 to 20% of the total composition.
3. A chewing gum according to claim 1 or claim 2 wherein the non- hygroscopic bulking agent comprises 60 to 80% of the total composition.
4. A chewing gum according to any of claims 1 to 3 wherein the ratio of gum base to non-hygroscopic bulking agent is in the range 1:3 to 1:5.
5. A chewing gum according to any of claims 1 to 4 wherein the non- hygroscopic bulking agent is an isomalt.
6. A chewing gum according to claim 5 wherein the isomalt is a mixture of 1- O-alpha-D-glucopyranosyl-D-mannitol and 6-O-alpha-D-glucopyranosyl- D-glucitol.
7. A chewing gum according to any of claims 1 to 6 containing ranitidine hydrochloride.
8. A chewing gum according to any of claims 1 to 7 containing 25 to 300mg ranitidine, expressed as the weight of free base, per dosage unit.
9. A chewing gum according to any of claims 1 to 8 in the form of a chewing gum tablet.
10. A process for the preparation of a ranitidine chewing gum composition as defined in claim 1 which comprises cooiing and blending a mixture of the gum base and bulking agent to produce a free flowing powder and blending with the ranitidine and other ingredients.
PCT/EP1996/005468 1995-12-09 1996-12-06 Chewing gum containing ranitidine WO1997021424A1 (en)

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
GB9525240.9 1995-12-09
GBGB9525240.9A GB9525240D0 (en) 1995-12-09 1995-12-09 Ranitidine compositions

Publications (1)

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

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Country Status (3)

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AU (1) AU1191497A (en)
GB (1) GB9525240D0 (en)
WO (1) WO1997021424A1 (en)

Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002051259A1 (en) * 2000-12-22 2002-07-04 Wm. Wrigley Jr. Company Coated chewing gum products containing various antacids
WO2002078459A1 (en) * 2001-03-29 2002-10-10 Societe Des Produits Nestles S.A. Chewing gum-containing tablet
US7078052B2 (en) 1999-04-06 2006-07-18 Wm. Wrigley Jr. Company Pharmaceutical chewing gum formulations
US7208186B2 (en) 2001-09-18 2007-04-24 Spi Pharma, Inc. Chewing gum formulation and method of making the same
CN100366146C (en) * 2002-03-08 2008-02-06 丘福.加托股份有限公司 A chewable toy for animals
WO2009007768A1 (en) * 2007-07-06 2009-01-15 Gumlink A/S Compressed tablet comprising polyol
WO2011080502A3 (en) * 2009-12-29 2011-11-10 Orexo Ab New pharmaceutical dosage form for the treatment of gastric acid-related disorders
WO2011080500A3 (en) * 2009-12-29 2011-11-10 Orexo Ab New pharmaceutical dosage form for the treatment of gastric acid-related disorders
WO2011080501A3 (en) * 2009-12-29 2011-11-10 Orexo Ab New pharmaceutical dosage form for the treatment of gastric acid-related disorders
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 (en) * 1978-02-25 1979-08-30 Nordstroem Rabbe Tablets produced from chewing gum granulate - obtained by cooling chewing gum until it becomes brittle
EP0151344A2 (en) * 1984-01-31 1985-08-14 Warner-Lambert Company A chewing gum composition, a process for preparing a chewing gum tablet therefrom, and a chewing gum tablet
WO1988008671A1 (en) * 1987-05-04 1988-11-17 Wm. Wrigley Jr. Company Improved hard coated sugarless chewing gum
CA2068366A1 (en) * 1991-05-10 1992-11-11 Angelo M. Morella Microcapsule composition and process
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 (en) * 1978-02-25 1979-08-30 Nordstroem Rabbe Tablets produced from chewing gum granulate - obtained by cooling chewing gum until it becomes brittle
EP0151344A2 (en) * 1984-01-31 1985-08-14 Warner-Lambert Company A chewing gum composition, a process for preparing a chewing gum tablet therefrom, and a chewing gum tablet
WO1988008671A1 (en) * 1987-05-04 1988-11-17 Wm. Wrigley Jr. Company Improved hard coated sugarless chewing gum
CA2068366A1 (en) * 1991-05-10 1992-11-11 Angelo M. Morella Microcapsule composition and process
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 (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7078052B2 (en) 1999-04-06 2006-07-18 Wm. Wrigley Jr. Company Pharmaceutical chewing gum formulations
WO2002051259A1 (en) * 2000-12-22 2002-07-04 Wm. Wrigley Jr. Company Coated chewing gum products containing various antacids
WO2002078459A1 (en) * 2001-03-29 2002-10-10 Societe Des Produits Nestles S.A. Chewing gum-containing tablet
US7208186B2 (en) 2001-09-18 2007-04-24 Spi Pharma, Inc. Chewing gum formulation and method of making the same
CN100366146C (en) * 2002-03-08 2008-02-06 丘福.加托股份有限公司 A chewable toy for animals
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 (en) * 2007-07-06 2009-01-15 Gumlink A/S Compressed tablet comprising polyol
WO2011080502A3 (en) * 2009-12-29 2011-11-10 Orexo Ab New pharmaceutical dosage form for the treatment of gastric acid-related disorders
WO2011080500A3 (en) * 2009-12-29 2011-11-10 Orexo Ab New pharmaceutical dosage form for the treatment of gastric acid-related disorders
WO2011080501A3 (en) * 2009-12-29 2011-11-10 Orexo Ab New pharmaceutical dosage form for the treatment of gastric acid-related disorders

Also Published As

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

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