Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Tablets – lozenges – or pills
Patent
1998-09-11
2000-08-22
Spear, James M.
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Tablets, lozenges, or pills
424468, 424474, 424475, 424482, 514770, 514781, 5147723, A61K 922, A61K 932, A61K 936
Patent
active
061068632
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
The present invention relates to sustained-release metal valproate tablets.
BACKGROUND
Sodium valproate is a useful drug widely used for the treatment of epilepsy and prevention of ictus epilepticus. The effective blood concentration of the drug is generally in the range of 50 to 100 .mu.g/ml. Since sodium valproate has a short biological half-life, it should be administered three times a day to keep the effective blood concentration. Such a short does interval being troublesome for patients, many efforts have been made to develop sustained-release preparations of sodium valproate, and several preparations have now been on the market. However, sodium valproate should be administered at a comparatively high daily dose reaching 1200 mg. Besides, it is water-soluble and highly hygroscopic. Hence, sustained-release tablets prepared by conventional techniques comprise a comparatively large proportion of release retarders, and the like, which increase the weight of the individual tablets, and are not always satisfactory.
Some proposals have been made on sustained-release tablets of sodium valproate.
For example, known are a method of preparing granules from a mixture of sodium valproate and magnesium aluminometasilicate using ethyl cellulose as a binder and then preparing sustained-releasing tablets (JP-A-62-81309) and a method of adding valproic acid in which ethyl cellulose has been dissolved therein to a mixture of Eudragit (a methacrylic acid copolymer) and sodium valproate, granulating the mixture, and preparing tablets (JP-A-60-41610). However, it is difficult to keep the blood concentration of sodium valproate for a long time according to these techniques.
JP-A-8-26977 discloses controlled-release oral preparations, which are applicable to general drugs, comprising a drug-containing core coated with a dissolution controlling coat comprising a mixture of a water-insoluble film-forming agent and an enteric film-forming agent. JP-A-8-26977 discloses a controlled-release oral preparation prepared by using a mixture of ethyl cellulose as a water-insoluble film-forming agent and a methacrylic acid-methyl methacrylate copolymer as an enteric film-forming agent. Judging from the specification as a whole, however, this invention relates to granules or powders the coat of which does not dissolve to release the drug in the stomach and the upper part of the small intestine but quickly dissolves to release the drug in the lower part of the digestive tract having a comparatively high pH, i.e., the lower part of the small intestine and the large intestine. Therefore, it is different from the present invention in not only purpose but also a preferred mixing ratio of ethyl cellulose and a methacrylic acid-methyl methacrylate copolymer.
Moreover, JP-A-4-235914 discloses a method of coating a core tablet containing sodium valproate with a coating agent comprising ethyl cellulose and hydroxypropylmethyl cellulose that is a water-soluble polymer.
The inventors of the present invention previously invented a sustained-release sodium valproate tablet which comprises a core tablet comprising sodium valproate having on the surface a coating layer coated with a coating agent comprising light silicic acid anhydride dispersed in ethyl cellulose (JP-A-6-40899). The sustained-release tablet exhibits satisfactory sustained release properties, showing substantially no difference in dissolution rate with pH change in a dissolution test using first and second solutions specified in The Pharmacopoeia of Japan. However, cases are sometimes observed with the sustained-release tablet having a release-controlling coating layer, wherein valproic acid is released from sodium valproate by the action of an acidic liquid having passed through the sustained-release coating layer in the digestive tract (stomach), and the valproic acid thus released dissolves and erodes the coating layer. If the tablet is taken during active peristalsis after a meal, it may follow that the coating layer is destroyed by the influences of the meal to
REFERENCES:
patent: 4913906 (1990-04-01), Friedman et al.
patent: 5019398 (1991-05-01), Daste
patent: 5169642 (1992-12-01), Brinker et al.
Okumura Mutsuo
Tsukune Tadashi
Ukigaya Tadashi
Nikken Chemicals Co., Ltd.
Spear James M.
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