Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Tablets – lozenges – or pills
Patent
1989-01-04
1993-02-23
Page, Thurman K.
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Tablets, lozenges, or pills
424465, 424466, 424486, 424487, 424489, 514925, 514960, 514961, 5147723, 514779, A61K 916, A61K 920
Patent
active
051888394
DESCRIPTION:
BRIEF SUMMARY
This invention relates to granules of cimetidine which are useful in the preparation of tablets and which have an improved flavour.
Cimetidine is a histamine H.sub.2 -antagonist. It has been described in U.K. Patent Specification 1,397,436. Cimetidine has been shown to be useful in the treatment of duodenal, gastric, recurrent and stomach ulceration, and reflux oesophagitis and in the management of Patients who are at high risk from haemorrhage of the upper gastrointestinal tract.
Cimetidine is known to have a pronounced bitter taste. This is not usually a problem when the dosage form employed is a capsule or a tablet designed to be swallowed, thereafter to disintegrate upon reaching the stomach. However, such dosage forms can be impractical when it is desired to administer a large amount of active ingredient, or to co-administer a relatively bulky second active ingredient such as an antacid or alginate. Moreover many individuals have difficulty in swallowing a solid dosage form.
A conventional approach to administering relatively large amounts of active ingredient in a solid dosage form is by means of a chewable tablet, i.e. a tablet which disintegrates in the mouth upon being chewed. Such a tablet also circumvents the problem of a solid dosage being difficult to swallow.
It will be appreciated that a ma)or requirement of such a dosage form is that it must be palatable, since an unpalatable formulation increases the risk of a patient neglecting to take the tablet. Such non-compliance with the dosing regimen will in turn delay or prevent the patient's recovery from the condition under treatment.
A further requirement of such a composition is that once the disintegrated tablet reaches the stomach, the individual particles should release the active ingredient rapidly and completely in order to ensure that substantially all of the active ingredient is absorbed; that is to say the formulation should be bioavailable.
In the case of cimetidine, because of its bitterness, the provision of such a dosage form represents a considerable problem.
Several solutions to the problem of the bitterness of cimetidine have been proposed. One proposal is disclosed in Japanese patent Application No. 67375/80 wherein there are described granules of cimetidine containing ethylcellulose preferably in the range of 15 to 85% (w/w) and particularly 50% (w/w) relative to the cimetidine. Such granules are described as having good stability to light, good dissolution characteristics and are stated not to have a bitter taste. These properties are stated to be specific to granules containing ethylcellulose; it is disclosed that methylcellulose does not impart such properties.
Another proposed solution is disclosed in Japanese Patent Application No. 86228/78 which similarly describes cimetidine granules containing a specific polymeric substance; in this case polyvinylacetal diethylaminoacetate. The particular granules exemplified in the specification of JP 86228/78 are characterised by having a high sugar content (approximately 75% by weight of the granules), and it is noteworthy that, of all those granules for which test results are provided in the specification demonstrating acceptable solubility and palatability characteristics, all contain approximately 75% by weight of granulated sugar (i.e. presumably sucrose).
Although both JP 67375/80 and JP 86228/78 address the problem of the bitterness of cimetidine, in neither case is it suggested that the granules described therein would be suitable for preparing chewable tablets. In the case of the granules disclosed in JP 86228/78, the use of a high loading of sucrose would be expected to be disadvantageous in a chewable dosage form in view of the well known ability of sucrose to promote tooth decay.
As far as we are aware, up until the time of the making of the present invention, no chewable tablets containing cimetidine have been marketed, or marketed to any significant extent, even though cimetidine per se has been on the market for approximately ten years, and is a well established drug.
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Dinner Dara L.
Lentz Edward T.
Page Thurman K.
Smith Kline & French Laboratories Ltd.
Spear James M.
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