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
  • A61K31/33—Heterocyclic compounds
  • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
  • A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
• • 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

• the present invention relates to low dosage formulations containing the histamine H 2 -receptor antagonist ranitidine and their use in the treatment of gastric disorders such as episodic heartburn.
• Ranitidine N-[2-[[[5-(dimethylamino)methyl-2-furanyl]methylJthio]ethyl]-N'- methyl-2-nitro-1,1-ethenediamine, and its physiologically acceptable salts are described and claimed in British Patent Specification No. 1565966, and a particular crystalline form of ranitidine hydrochloride is described and claimed in British Patent Specification No. 2084580.
• 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 ranitidine.
• US Patent No. 5229137 describes the use of a combination of ranitidine and an antacid for the treatment of episodic heartburn.
• H 2 -antagonists such as ranitidine
• an antacid needs to be administered with the Hr-antagonist in order to obtain rapid relief.
• the doses used in the combination are between 100 and 150mg.
• EP0193400 Compositions containing reduced doses of H 2 -antagonists are described in EP0193400 and W093/12779.
• EP0193400 describes a combination of an H 2 _antagonist, such as ranitidine, and sodium polyacrylate for use in the treatment of gastritis or gastro-duodenal ulcers. According to EP0193400, the synergistic effect between the H 2 -antagonist and polyacrylate affords the possibility of the lower doses of H 2 -antagonist being used.
• W093/12779 describes the use of a combination of an Hr-antagonist, including ranitidine, and an antacid in the treatment of gastric disorders, where the combination is buffered to confer a pH substantially equal to that of the pKa of the H 2 -antagonist and where the dose of the H 2 -antagonist per unit dosage form is less than 25mg.
• the lower dose is said to be effective since the combination of active agents increases bioavailability of the Hr-antagonist at the local stomach wall receptor site.
• EP0492247 also describes a composition having a reduced dose of H 2 _antagonist for the treatment of heartburn etc.
• the composition uses a combination of water-soluble H 2 -antagonist and an effervescent delivery system, such as an alkali metal bicarbonate and citric acid.
• the use of the effervescent delivery system is said to decrease the time for onset of action of the H 2 _antagonist and increases its potency such that the formulation requires about twenty-five per cent of the H 2 -antagonist dosage currently prescribed for the treatment of active duodenal ulcer.
• the effervescent delivery system reduces the dosage from 150mg to less than about 37.5mg.
• Dosage levels between 50 and 600mg, such as 150 and 300mg, of ranitidine when administered alone are conventionally regarded as conferring therapeutic benefit.
• the present invention provides an oral pharmaceutical composition, such as a tablet, comprising ranitidine, or a physiologically acceptable salt thereof, as the sole active ingredient, characterised in that the dose of ranitidine per unit dosage form is between 10 and 30mg, such as 25mg, expressed as the weight of free base.
• a swallow tablet comprising ranitidine, or a physiologically acceptable salt thereof, as the sole active ingredient, characterised in that the dose of ranitidine per unit dosage form is between 10 and 30mg, such as 25mg, expressed as the weight of free base.
• the present invention provides a method of treating minor gastrointestinal disorders associated with excess acid secretion which comprises administering to a patient in need of such, an oral pharmaceutical composition which consists essentially of ranitidine, or a physiologically acceptable salt thereof, as the sole active ingredient characterised in that the dose of ranitidine per unit dosage form is between 10 and 30mg, such as 25mg, expressed as the weight of free base.
• compositions according to the invention are substantially free from antacids, a polyacrylate or an effervescent delivery system.
• Ranitidine may be employed in the tablets 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 ranitidine is the hydrochloride.
• Ranitidine may be employed in the tablets according to the invention in conventional form or coated or encapsulated forms of ranitidine may be used. Suitable coated and encapsulated forms are described in, for example, EP538034, EP523847, W092/21328, EP473431, EP459695, EP349103, CA2068366 and US5084278. Ranitidine resin adsorbates as described in UK2218333 may also be incorporated into the tablets according to the present invention.
• ranitidine and its salts are used in conventional form.
• 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 30mg per dosage unit (for example per tablet), e.g. 25mg, expressed as the weight of free base.
• the unit dose (for example contained in one tablet according to the invention) may be administered up to, for example, 12 times a day depending upon the nature and severity of the conditions being treated, and the age and weight of the patient.
• minor gastrointestinal disorders associated with excess acid secretion such as, for example, acid indigestion, over-indulgence of food or drink (e.g. alcoholic beverages), acid stomach, sour stomach, waterbrash/regurgitation, heartburn, such as episodic heartburn, nocturnal heartburn, and meal-induced heartburn, gastritis and dyspepsia
• a 10-30mg dose of ranitidine e.g. a 25mg dose, expressed as the weight of free base, may be administered up to 12 times a day, for example 6 times a day, as and when required.
• compositions according to the invention may also contain other excipients conventional to the art such as fillers, binders, disintegrants, lubricants and dessicants. Suitable excipients are well-known to those skilled in the art.
• Suitable binders include methylcellulose, sodium carboxymethylcellulose, hydroxypropyl methylcellulose, alginic acid, ethylcellulose, acacia, gelatin, pregelatinised starch, sucrose syrup, polyvinylpyrrolidone (povidone) and guar gum.
• Suitable lubricants include magnesium stearate, zinc stearate, calcium stearate, stearic acid, sodium stearyl fumarate, hydrogenated vegetable oils, glyceryl palmitostearate, glyceryl behenate, sodium benzoate, sodium lauryl sulphate, magnesium lauryl sulphate, mineral oil, talc and mixtures thereof.
• Magnesium stearate is a preferred lubricant.
• Suitable dessicants include silica gel.
• Suitable fillers include microcrysalline cellulose.
• Suitable disintegrants include croscarmellose sodium.
• Such chewable tablets comprise ranitidine, or a physiologically acceptable salt thereof, a chewable base selected from sucrose, glucose, lactose, maltose, or a mixture thereof, a flavouring and, optionally an intense sweetener.
• the chewable tablets may be prepared using the conventional stages of mixing, granulation, drying, blending, compression and packing.
• Suitable swallow tablet cores may be prepared in a conventional manner, for example in a similar manner to that described in British Patent Specification No.
• ranitidine or its salt a lubricant, such as magnesium stearate and optionally a pharmaceutically acceptable disintegrant, such as croscarmellose sodium, are mixed and compressed into tablet cores.
• a lubricant such as magnesium stearate
• a pharmaceutically acceptable disintegrant such as croscarmellose sodium
• Swallow tablets are conventionally film-coated according to conventional procedures either by aqueous or organic techniques.
• a preferred film coat is described in British Patent specification No. 2218336 which is incorporated herein by reference.
• Opaspray white K-1-7000 is a suspension of titanium dioxide and hydroxypropyl cellulose in industrial methylated spirits.
• Opadry Yellow Y S-1 -12606 is a mixture of hydroxypropyl methylcellulose 2910, titanium dioxide, triacetin and iron oxide yellow. Both Opaspray and Opadry are the tradenames of Colorcon Inc., West Point, Philadelphia, USA.
• Reference Example 1

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• Engineering & Computer Science (AREA)
• Bioinformatics & Cheminformatics (AREA)
• Chemical Kinetics & Catalysis (AREA)
• General Chemical & Material Sciences (AREA)
• Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
• Organic Chemistry (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
• Medicinal Preparation (AREA)
• Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Applications Claiming Priority (3)

Publications (1)

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Family Applications (1)

Country Status (11)

Family Cites Families (3)

• 1994
  • 1994-04-12 GB GB9407235A patent/GB9407235D0/en active Pending
• 1995
  • 1995-04-10 CN CN95192537A patent/CN1146150A/zh active Pending
  • 1995-04-10 JP JP7526068A patent/JPH10502331A/ja active Pending
  • 1995-04-10 CA CA002187651A patent/CA2187651A1/en not_active Abandoned
  • 1995-04-10 BR BR9507312A patent/BR9507312A/pt unknown
  • 1995-04-10 ZA ZA952931A patent/ZA952931B/xx unknown
  • 1995-04-10 NZ NZ283354A patent/NZ283354A/en unknown
  • 1995-04-10 AU AU21380/95A patent/AU690664B2/en not_active Ceased
  • 1995-04-10 WO PCT/EP1995/001271 patent/WO1995027486A1/en not_active Application Discontinuation
  • 1995-04-10 EP EP95914346A patent/EP0755251A1/en not_active Withdrawn
• 1996
  • 1996-10-11 KR KR1019960705716A patent/KR970702034A/ko not_active Application Discontinuation

Non-Patent Citations (1)

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