WO1995008997A1 - Ranitidine and calcium carbonate pharmaceutical combination product - Google Patents

Ranitidine and calcium carbonate pharmaceutical combination product Download PDF

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Publication number
WO1995008997A1
WO1995008997A1 PCT/US1994/011132 US9411132W WO9508997A1 WO 1995008997 A1 WO1995008997 A1 WO 1995008997A1 US 9411132 W US9411132 W US 9411132W WO 9508997 A1 WO9508997 A1 WO 9508997A1
Authority
WO
WIPO (PCT)
Prior art keywords
pharmaceutical composition
ranitidine
calcium carbonate
unit dose
composition
Prior art date
Application number
PCT/US1994/011132
Other languages
French (fr)
Inventor
Mark Alan Sirgo
Original Assignee
Glaxo Wellcome Inc.
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 Glaxo Wellcome Inc. filed Critical Glaxo Wellcome Inc.
Priority to NZ274713A priority Critical patent/NZ274713A/en
Priority to CA002168846A priority patent/CA2168846A1/en
Priority to AU79253/94A priority patent/AU677108B2/en
Priority to SK405-96A priority patent/SK40596A3/en
Priority to JP7510481A priority patent/JPH09503212A/en
Priority to EP94929984A priority patent/EP0721338A1/en
Priority to PL94316855A priority patent/PL316855A1/en
Publication of WO1995008997A1 publication Critical patent/WO1995008997A1/en
Priority to BG100456A priority patent/BG100456A/en
Priority to NO961297A priority patent/NO961297D0/en

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/06—Aluminium, calcium or magnesium; Compounds thereof, e.g. clay
    • A61K33/10—Carbonates; Bicarbonates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants

Definitions

  • Ranitidine chemically identified as N-[2-[[[5-(dimethylamino)methyl-2- furany]methyl]thio]ethyl]-N'-methyl-2-nitro-1 ,1-ethenediamine (see U.S. Patents 4,128,658; 4,521 ,431; 4,585,790 and 4,672,133 incorporated herein by reference), is an antagonist to histamine H2 receptors.
  • the term "ranitidine” refers to the free base and the pharmaceutically acceptable acid addition salts thereof unless otherwise noted. This drug is widely used in the treatment of duodenal ulcers in humans in the form of the hydrochloride salt. While the drug is generally given orally or by injection, the oral route is preferred.
  • Ranitidine HCI is sold under the trademark Zantac® by Glaxo Inc. of Research Triangle Park, North Carolina.
  • Calcium carbonate is used as an antacid for fast relief of acid indigestion, heartburn, sour stomach and upset stomach associated with those symptoms. It is used in antacids sold commercially under the trademark Turns® by SmithKline Beecham Consumer Brands of Pittsburgh, Pennsylvania and is a buffer in Ascriptin® analgesic in combination with aspirin, magnesium hydroxide and aluminum hydroxide as sold by Rorer Consumer Pharmaceuticals of Fort Washington, Pennsylvania.
  • U.S. Patent 4,650,669 to Alexander describes formulations for pharmaceuticals containing calcium carbonate.
  • compositions having both ranitidine or another H2 receptor antagonist and NaHCO ⁇ include the effervescent compositions described by Schaeffer in U.S. Patent 5,102,665.
  • An effervescent pharmaceutical comprising an antacid effervescent couple, an antacid and an histamine ⁇ -antagonist is described in US Patent 4,824, 664 issued to Tarral.
  • Other disclosures of combinations H2- antagonists and antacids are found in European Patent Specification No. 286,781.
  • PCT Publication WO/92/00102 published 9 January 1992 to Davis describes co- administration of a histamine H2-receptor antagonist and antacid for the treatment of gastric disorder, e.g., Example 17 thereof listing calcium carbonate.
  • PCT Publication WO 93/12779 published 8 July 1993 to Davis describes co- administration of a histamine H2-receptor antagonist and antacid for the treatment of gastric disorder, e.g., Example 14 thereof listing calcium carbonate.
  • US Patent 5,229,137 issued to Wolfe describes the co-administration of a histamine H 2 -receptor antagonist and an antacid for the treatment of episodic heartburn, e.g., Example IV thereof relating to the co-administration of ranitidine and Turns® tablets.
  • compositions such as tablets containing both calcium carbonate and ranitidine.
  • the composition provides relief from many gastrointestinal diseases and symptoms.
  • composition of the invention is substantially free of acid, e.g., acid as may be used as part of an acid-base couple to produce effervescence.
  • ranitidine is used in the present invention as its hydrochloride and in the Form 2 crystalline form.
  • Calcium carbonate also known as carbonic acid calcium salt, occurs in nature as the minerals aragonite, calcite and vaterite.
  • the calcium carbonate may be used in the calcite form and be essentially free of the aragonite crystal form.
  • the calcium carbonate employed in the present invention can be in the particulate form. Suitable particulate calcium carbonate is Albaglos®, supplied by Pfizer, at its facility in Adams, Massachusetts. Albaglos is a precipitated calcium carbonate made by starting with high quality CaCU3 and burning it to create CO2 and CaO (lime). The CaO is dissolved in H2O to create a milk of lime solution (CaCOH/2). The CO2 (which was previously captured) is injected into the solution, causing pure crystals of CaC ⁇ 3 to precipitate.
  • excipients such as flavorings, taste masking agents, lubricants, surfactants, binders or coloring agents and the like may be optionally added into the tablet composition of the present invention.
  • Typical flavorings include grapefruit, lemon, mint and orange, and/or sweeteners such as aspartame or sodium saccharin.
  • a small amount of dioctylsodium sulfosuccinate (DOSS also known as docusate sodium) solution, for instance, may be added as a surfactant, and/or a small amount of fumaric acid may be added as a lubricant.
  • DOSS dioctylsodium sulfosuccinate
  • These excipients are usually added in the amount of 0.001 % to 100% weight/weight, more particularly 0.01% to 60% weight/weight, of the CaC ⁇ 3.
  • Taste-masking ingredients and formulation techniques known in the art may be applied in the pharmaceutical composition of the invention.
  • examples include those in UK Patent Specification Nos 2198352 (liquid preparations), 2219940 (effervescent tablets), 2218333 (ranitidine resinate), 2218336 (film-coated tablets), 2229094 (gelatin capsules), 2262445 (pulsed-release formulation), European Patent Specification Nos 349103, 459695, 473431 , 523847 and 538034 (chewable tablets), 542364 (controlled-release formulations), International Patent Specification Nos W092/21328 (chewable compositions), WO94/08560 (chewable tablets), W094/05260 (aqueous compositions), WO94/08576 (lipid-coated granules), Canadian Patent Specification No. 2068366 (taste-masked powder), United States Patent Specification Nos 5169864 and 5304571 (aqueous compositions) which patent specifications are incorporated herein by reference.
  • Suitable binders for use in tablet preparation include methylcellulose, sodium carboxymethylcellulose, hydroxypropyl methylcellulose, alginic acid, ethylcellulose, acacia, gelatin, pregelatinized starch, sucrose syrup, polyvinylpyrrolidone and guar gum.
  • a particular binder is polyvinylpyrrolidone (povidone).
  • Suitable lubricants for use in tablet preparation include magnesium stearate, zinc stearate, calcium stearate, stearic acid, sodium stearyl fumerate, hydrogenated vegetable oils, glyceryl palmitosterate, glyceryl behenate, sodium benzoate, sodium lauryl sulphate, magnesium lauryl sulphate, mineral oil, talc and mixtures thereof.
  • Magnesium stearate is a particular lubricant.
  • Suitable dessicants for use in tablet preparation include silica gel.
  • Ranitidine may be used in the composition of the present invention in an amount of 25 to less than 100 mg per dose, e.g., about 30 to 90 mg calculated as ranitidine base. In particular, a dose of about 50 to 80 mg, e.g., 75 mg may be used.
  • Calcium carbonate may be used in the unit dose composition of the present invention in an amount of about 250 mg to 1000 mg to provide an antacid neutralizing capacity of about 5 to 40 mEq.
  • a particular dose is about 500 mg of calcium carbonate.
  • the unit dose may be administered up to, for example, 6 times a day depending upon the unit dose used, the nature and severity 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 25-95 mg, e.g., 40-75 mg ranitidine expressed as the weight of free base, such as 83.7 mg ranitidine hydrochloride, administered up to 6 times a day as and when required.
  • reference to treatment is intended to include prophylaxis as well as the alleviation of established symptoms.
  • the pharmaceutical composition of the invention may be in the form of a solid particulate, e.g., a powder, with the 2 ingredients present homogeneously so that the unit dose would be a measure such as a teaspoonful.
  • the composition can be used in the form of a liquid where the unit dose would be a liquid measure, e.g., 10 ml.
  • the composition of the invention is used as a pre-formed unit dose such as a tablet, bi-layer tablet with separate location for the ranitidine and the calcium carbonate, capsule or other particular modification such as a gelcap, caplet, tongue tablet or chewable tablet.
  • the active ingredients and excipients may be subject to dry slugging, wet granulation or dry blending followed by compression into tablets using an appropriate tablet press fitted with suitable punches.
  • the active ingredients and inactive excipients are mixed and filled into gelatin capsules as is conventional in the art.
  • the present invention provides the use of an oral pharmaceutical composition comprising ranitidine, or a pharmaceutically acceptable salt thereof, and an antacid for the manufacture of a medicament of the treatment of conditions where there is an advantage in lowering gastric acidity, characterized in that the antacid comprises calcium carbonate.
  • ranitidine hydrochloride 83.7 grams calcium carbonate 500 grams starch 80 grams powdered lactose 80 grams talc 20 grams
  • the above ingredients are combined, mixed and then compressed into slugs.
  • the slugs may then be ground to form granules that will pass through a 14 to 16 mesh screen.
  • the granules may then be recompressed into tablets using a suitable compression mold to form 1000 tablets, each weighing about 763.7 mg.
  • Example 2 The following is a bi-layer tablet to cover any incompatibilities between the ingredients.
  • ranitidine hydrochloride (taste-masked if required) is blended with the microcrystalline cellulose and magnesium stearate.
  • Magnesium stearate USNF 4.0 The calcium carbonate and sucrose for the antacid layer are granulated together in a conventional manner.
  • the calcium carbonate/sucrose granule is blended with the flavor sweetener and magnesium stearate.
  • ranitidine containing granules and antacid granules are compressed together as a bi-layer tablet on a suitable compression machine.

Abstract

A pharmaceutical composition for gastrointestinal conditions comprising ranitidine and calcium carbonate.

Description

RANITIDINE AND CALCIUM CARBONATE
PHARMACEUTICAL COMBINATION PRODUCT
BACKGROUND OF THE INVENTION
Ranitidine, chemically identified as N-[2-[[[5-(dimethylamino)methyl-2- furany]methyl]thio]ethyl]-N'-methyl-2-nitro-1 ,1-ethenediamine (see U.S. Patents 4,128,658; 4,521 ,431; 4,585,790 and 4,672,133 incorporated herein by reference), is an antagonist to histamine H2 receptors. As used herein the term "ranitidine" refers to the free base and the pharmaceutically acceptable acid addition salts thereof unless otherwise noted. This drug is widely used in the treatment of duodenal ulcers in humans in the form of the hydrochloride salt. While the drug is generally given orally or by injection, the oral route is preferred. Ranitidine HCI is sold under the trademark Zantac® by Glaxo Inc. of Research Triangle Park, North Carolina.
Calcium carbonate is used as an antacid for fast relief of acid indigestion, heartburn, sour stomach and upset stomach associated with those symptoms. It is used in antacids sold commercially under the trademark Turns® by SmithKline Beecham Consumer Brands of Pittsburgh, Pennsylvania and is a buffer in Ascriptin® analgesic in combination with aspirin, magnesium hydroxide and aluminum hydroxide as sold by Rorer Consumer Pharmaceuticals of Fort Washington, Pennsylvania. U.S. Patent 4,650,669 to Alexander describes formulations for pharmaceuticals containing calcium carbonate.
Pharmaceuticals having both ranitidine or another H2 receptor antagonist and NaHCOβ include the effervescent compositions described by Schaeffer in U.S. Patent 5,102,665. An effervescent pharmaceutical comprising an antacid effervescent couple, an antacid and an histamine ^-antagonist is described in US Patent 4,824, 664 issued to Tarral. Other disclosures of combinations H2- antagonists and antacids are found in European Patent Specification No. 286,781.
PCT Publication WO/92/00102 published 9 January 1992 to Davis describes co- administration of a histamine H2-receptor antagonist and antacid for the treatment of gastric disorder, e.g., Example 17 thereof listing calcium carbonate. PCT Publication WO 93/12779 published 8 July 1993 to Davis describes co- administration of a histamine H2-receptor antagonist and antacid for the treatment of gastric disorder, e.g., Example 14 thereof listing calcium carbonate.
US Patent 5,229,137 issued to Wolfe describes the co-administration of a histamine H2-receptor antagonist and an antacid for the treatment of episodic heartburn, e.g., Example IV thereof relating to the co-administration of ranitidine and Turns® tablets.
SUMMARY OF THE INVENTION
Pharmaceutical compositions such as tablets containing both calcium carbonate and ranitidine. The composition provides relief from many gastrointestinal diseases and symptoms.
DETAILED DESCRIPTION OF THE INVENTION
The composition of the invention is substantially free of acid, e.g., acid as may be used as part of an acid-base couple to produce effervescence.
Ranitidine
Preferably, the ranitidine is used in the present invention as its hydrochloride and in the Form 2 crystalline form.
Calcium Carbonate
Calcium carbonate, also known as carbonic acid calcium salt, occurs in nature as the minerals aragonite, calcite and vaterite. In the present invention, the calcium carbonate may be used in the calcite form and be essentially free of the aragonite crystal form. The calcium carbonate employed in the present invention can be in the particulate form. Suitable particulate calcium carbonate is Albaglos®, supplied by Pfizer, at its facility in Adams, Massachusetts. Albaglos is a precipitated calcium carbonate made by starting with high quality CaCU3 and burning it to create CO2 and CaO (lime). The CaO is dissolved in H2O to create a milk of lime solution (CaCOH/2). The CO2 (which was previously captured) is injected into the solution, causing pure crystals of CaCθ3 to precipitate.
Other Ingredients
Other known pharmaceutical excipients such as flavorings, taste masking agents, lubricants, surfactants, binders or coloring agents and the like may be optionally added into the tablet composition of the present invention. Typical flavorings include grapefruit, lemon, mint and orange, and/or sweeteners such as aspartame or sodium saccharin. A small amount of dioctylsodium sulfosuccinate (DOSS also known as docusate sodium) solution, for instance, may be added as a surfactant, and/or a small amount of fumaric acid may be added as a lubricant. These excipients are usually added in the amount of 0.001 % to 100% weight/weight, more particularly 0.01% to 60% weight/weight, of the CaCθ3.
Taste-masking ingredients and formulation techniques known in the art may be applied in the pharmaceutical composition of the invention. Examples include those in UK Patent Specification Nos 2198352 (liquid preparations), 2219940 (effervescent tablets), 2218333 (ranitidine resinate), 2218336 (film-coated tablets), 2229094 (gelatin capsules), 2262445 (pulsed-release formulation), European Patent Specification Nos 349103, 459695, 473431 , 523847 and 538034 (chewable tablets), 542364 (controlled-release formulations), International Patent Specification Nos W092/21328 (chewable compositions), WO94/08560 (chewable tablets), W094/05260 (aqueous compositions), WO94/08576 (lipid-coated granules), Canadian Patent Specification No. 2068366 (taste-masked powder), United States Patent Specification Nos 5169864 and 5304571 (aqueous compositions) which patent specifications are incorporated herein by reference.
Suitable binders for use in tablet preparation include methylcellulose, sodium carboxymethylcellulose, hydroxypropyl methylcellulose, alginic acid, ethylcellulose, acacia, gelatin, pregelatinized starch, sucrose syrup, polyvinylpyrrolidone and guar gum. A particular binder is polyvinylpyrrolidone (povidone).
Suitable lubricants for use in tablet preparation include magnesium stearate, zinc stearate, calcium stearate, stearic acid, sodium stearyl fumerate, hydrogenated vegetable oils, glyceryl palmitosterate, glyceryl behenate, sodium benzoate, sodium lauryl sulphate, magnesium lauryl sulphate, mineral oil, talc and mixtures thereof. Magnesium stearate is a particular lubricant.
Suitable dessicants for use in tablet preparation include silica gel.
Dose
Ranitidine may be used in the composition of the present invention in an amount of 25 to less than 100 mg per dose, e.g., about 30 to 90 mg calculated as ranitidine base. In particular, a dose of about 50 to 80 mg, e.g., 75 mg may be used.
Calcium carbonate may be used in the unit dose composition of the present invention in an amount of about 250 mg to 1000 mg to provide an antacid neutralizing capacity of about 5 to 40 mEq. A particular dose is about 500 mg of calcium carbonate.
The unit dose may be administered up to, for example, 6 times a day depending upon the unit dose used, the nature and severity 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 25-95 mg, e.g., 40-75 mg ranitidine expressed as the weight of free base, such as 83.7 mg ranitidine hydrochloride, administered up to 6 times a day as and when required. It will be appreciated that reference to treatment is intended to include prophylaxis as well as the alleviation of established symptoms.
Pharmaceutical Presentation
The pharmaceutical composition of the invention may be in the form of a solid particulate, e.g., a powder, with the 2 ingredients present homogeneously so that the unit dose would be a measure such as a teaspoonful. Alternatively, the composition can be used in the form of a liquid where the unit dose would be a liquid measure, e.g., 10 ml. Most conveniently, the composition of the invention is used as a pre-formed unit dose such as a tablet, bi-layer tablet with separate location for the ranitidine and the calcium carbonate, capsule or other particular modification such as a gelcap, caplet, tongue tablet or chewable tablet.
Tableting
To produce tablets of the composition according to the present invention, the active ingredients and excipients may be subject to dry slugging, wet granulation or dry blending followed by compression into tablets using an appropriate tablet press fitted with suitable punches.
Capsules
To produce capsules of the composition according to the present invention, the active ingredients and inactive excipients are mixed and filled into gelatin capsules as is conventional in the art.
In a further or alternative aspect, the present invention provides the use of an oral pharmaceutical composition comprising ranitidine, or a pharmaceutically acceptable salt thereof, and an antacid for the manufacture of a medicament of the treatment of conditions where there is an advantage in lowering gastric acidity, characterized in that the antacid comprises calcium carbonate. Example 1
The following ingredients are mixed and formulated into tablets in a conventional manner.
ranitidine hydrochloride 83.7 grams calcium carbonate 500 grams starch 80 grams powdered lactose 80 grams talc 20 grams
763.7 grams
The above ingredients are combined, mixed and then compressed into slugs. The slugs may then be ground to form granules that will pass through a 14 to 16 mesh screen. The granules may then be recompressed into tablets using a suitable compression mold to form 1000 tablets, each weighing about 763.7 mg.
Example 2 The following is a bi-layer tablet to cover any incompatibilities between the ingredients.
Ranitidine Layer mg/tablet
Ranitidine hydrochloride 84.0 Microcrystalline cellulose USP 64.5 Magnesium stearate USNF 1.5
The ranitidine hydrochloride (taste-masked if required) is blended with the microcrystalline cellulose and magnesium stearate.
Antacid Layer mg/tablet
Calcium carbonate precipitated USP 500.0
Sucrose 346.0
Flavor/sweetener qs
Magnesium stearate USNF 4.0 The calcium carbonate and sucrose for the antacid layer are granulated together in a conventional manner. The calcium carbonate/sucrose granule is blended with the flavor sweetener and magnesium stearate.
The ranitidine containing granules and antacid granules are compressed together as a bi-layer tablet on a suitable compression machine.

Claims

What is claimed is:
1. A pharmaceutical composition comprising ranitidine in an amount of 25 to less than 100 mg per dose and calcium carbonate.
2. The pharmaceutical composition of Claim 1 , wherein the composition is substantially free of acid.
3. The pharmaceutical composition of Claim 1 , wherein said ranitidine is in the form of ranitidine hydrochloride salt.
4. The pharmaceutical composition of Claim 1 , wherein said ranitidine is present in an amount of about 30 to 90 mg, calculated as ranitidine free base, per unit dose of said pharmaceutical composition.
5. The pharmaceutical composition of Claim 1 , wherein said ranitidine is present in an amount of 25 or 75 mg, calculated as ranitidine free base, per unit dose of said pharmaceutical composition.
6. The pharmaceutical composition of Claim 1, wherein said calcium carbonate is present in an amount of about 250 to 1000 mg per unit dose of said pharmaceutical composition.
7. The pharmaceutical composition of Claim 1, in the form of a solid particulate.
8. The pharmaceutical composition of Claim 1 , in the form of a liquid.
9. The pharmaceutical composition of Claim 1 , in the form of a solid unit dose.
10. The pharmaceutical composition of Claim 9, wherein said solid unit dose is a tablet or capsule.
11. The pharmaceutical composition of Claim 1, further comprising one or more flavoring agents, taste masking agents, binders, lubricants, surfactants or coloring agents.
12. The pharmaceutical composition of Claim 1, in the form of a bi-layer tablet.
13. The pharmaceutical composition of Claim 1, wherein said composition contains only said ranitidine and calcium carbonate as active ingredients.
14. A method of treating episodic heartburn, nocturnal heartburn, meal- induced heartburn, gastritis, dyspepsia or gastrointestinal symptoms associated with the overindulgence of food and drink which comprises administering to a human in need thereof, the pharmaceutical composition of Claim 1.
15. A method of treating and preventing duodenal ulcers, pathological hypersecretory conditions, gastric ulcers, gastro-esophageal reflux or erosive esophagitis which comprises administering to a human in need thereof, the pharmaceutical composition of Claim 1.
PCT/US1994/011132 1993-09-30 1994-09-29 Ranitidine and calcium carbonate pharmaceutical combination product WO1995008997A1 (en)

Priority Applications (9)

Application Number Priority Date Filing Date Title
NZ274713A NZ274713A (en) 1993-09-30 1994-09-29 Pharmaceutical compositions comprising ranitidine and calcium carbonate
CA002168846A CA2168846A1 (en) 1993-09-30 1994-09-29 Ranitidine and calcium carbonate pharmaceutical combination product
AU79253/94A AU677108B2 (en) 1993-09-30 1994-09-29 Ranitidine and calcium carbonate pharmaceutical combination product
SK405-96A SK40596A3 (en) 1993-09-30 1994-09-29 A pharmaceutical composition
JP7510481A JPH09503212A (en) 1993-09-30 1994-09-29 Ranitidine and calcium carbonate pharmaceutical composition
EP94929984A EP0721338A1 (en) 1993-09-30 1994-09-29 Ranitidine and calcium carbonate pharmaceutical combination product
PL94316855A PL316855A1 (en) 1993-09-30 1994-09-29 Pharmaceutic mixture of ranitidin and calcium carbonate
BG100456A BG100456A (en) 1993-09-30 1996-03-27 Ranitidine and calcium carbonate pharmaceutical product
NO961297A NO961297D0 (en) 1993-09-30 1996-03-29 Ranitidine and calcium carbonate pharmaceutical product

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US12951793A 1993-09-30 1993-09-30
US08/129,517 1993-09-30

Publications (1)

Publication Number Publication Date
WO1995008997A1 true WO1995008997A1 (en) 1995-04-06

Family

ID=22440376

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1994/011132 WO1995008997A1 (en) 1993-09-30 1994-09-29 Ranitidine and calcium carbonate pharmaceutical combination product

Country Status (17)

Country Link
EP (1) EP0721338A1 (en)
JP (1) JPH09503212A (en)
CN (1) CN1140996A (en)
AU (1) AU677108B2 (en)
BG (1) BG100456A (en)
CA (1) CA2168846A1 (en)
CZ (1) CZ76996A3 (en)
HU (1) HUT75061A (en)
IL (1) IL111094A0 (en)
NO (1) NO961297D0 (en)
NZ (1) NZ274713A (en)
OA (1) OA10717A (en)
PL (1) PL316855A1 (en)
SG (1) SG44715A1 (en)
SK (1) SK40596A3 (en)
WO (1) WO1995008997A1 (en)
ZA (1) ZA947553B (en)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP5560701B2 (en) * 2008-12-26 2014-07-30 ライオン株式会社 Ranitidine-containing pharmaceutical solid preparation and method for producing ranitidine-carrying particles

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2636532A1 (en) * 1988-09-20 1990-03-23 Glaxo Group Ltd PHARMACEUTICAL COMPOSITIONS
WO1992000102A1 (en) * 1990-06-22 1992-01-09 Beecham Group Plc Novel treatment
WO1993012779A1 (en) * 1991-12-20 1993-07-08 Smithkline Beecham Plc Compositions containing histamine-h2-receptor antagonists at low dosage
US5229137A (en) * 1992-05-06 1993-07-20 Brigham And Women's Hospital, Inc. Methods and pharmaceutical compositions for treating episodic heartburn

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2636532A1 (en) * 1988-09-20 1990-03-23 Glaxo Group Ltd PHARMACEUTICAL COMPOSITIONS
WO1992000102A1 (en) * 1990-06-22 1992-01-09 Beecham Group Plc Novel treatment
WO1993012779A1 (en) * 1991-12-20 1993-07-08 Smithkline Beecham Plc Compositions containing histamine-h2-receptor antagonists at low dosage
US5229137A (en) * 1992-05-06 1993-07-20 Brigham And Women's Hospital, Inc. Methods and pharmaceutical compositions for treating episodic heartburn

Also Published As

Publication number Publication date
IL111094A0 (en) 1994-11-28
AU7925394A (en) 1995-04-18
CN1140996A (en) 1997-01-22
AU677108B2 (en) 1997-04-10
HU9600810D0 (en) 1996-05-28
EP0721338A1 (en) 1996-07-17
PL316855A1 (en) 1997-02-17
NO961297L (en) 1996-03-29
BG100456A (en) 1996-11-29
CA2168846A1 (en) 1995-04-06
SK40596A3 (en) 1997-02-05
CZ76996A3 (en) 1996-10-16
HUT75061A (en) 1997-03-28
NO961297D0 (en) 1996-03-29
NZ274713A (en) 1997-10-24
ZA947553B (en) 1995-05-26
OA10717A (en) 2002-12-09
JPH09503212A (en) 1997-03-31
SG44715A1 (en) 1997-12-19

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