Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Tablets – lozenges – or pills
Patent
1997-11-12
2000-03-28
Williamson, Michael A.
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Tablets, lozenges, or pills
A61K 924
Patent
active
060428473
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD OF THE INVENTION
The invention belongs to the field of pharmaceutical industry and relates to a novel medicinal preparation with prolonged action for peroral application (sustained release tablets) based on a combination of an amorphous active ingredient, water-soluble polymer polyvinylpyrrolidone, cellulose ethers and a mixture of mono-, di- and triglycerides, an ester of hydroxypropylmethylcellulose with phthalic anhydride or a copolymer based on methacrylic acid and ethyl acrylate.
Particularly, the invention relates to a novel three-phase pharmaceutical form with a constant and controlled release of an amorphous active ingredient stabilized with polymers for a single daily peroral application such as tablets and capsules. A three-phase pharmaceutical form with constant and controlled release of an amorphous active ingredient for a single daily peroral application is especially suitable for active ingredients existing in amorphous form or in one or more polymorphous forms, which exhibit poor solubility in crystal form depending on the polymorphous form, particle size and specific surface area of the active ingredient. The active ingredient can be used in amorphous or any polymorphous form which is converted into the amorphous form during the manufacturing process of the three-phase pharmaceutical form of the invention. The three-phase pharmaceutical form with constant and controlled release of the amorphous active ingredient for a single daily peroral application contains a core consisting of a first and a second phase and a coating representing the third phase. The three-phase pharmaceutical form contains as the first phase an amorphous active ingredient, the water-soluble polymer polyvinylpyrrolidone and a cellulose ether as carriers of the amorphous active ingredient and simultaneously as inhibitors of crystallization of the amorphous active ingredient as well as a surfactant improving the solubility of the active ingredient and promoting the absorption of the amorphous active ingredient from the gastrointestinal tract; as the second phase it contains sustained-release agents such as cellulose ether and a mixture of mono-, di- and triglycerides, and the third phase is represented by a poorly soluble or gastro-resistant film coating, which in the first few hours after the application controls the release of the active ingredient and can consist of an ester of hydroxypropylmethylcellulose with phthalic anhydride or of a copolymerizate based on methacrylic acid and ethyl acrylate.
TECHNICAL PROBLEM
There exists a constant need to develop pharmaceutical forms in which solubility and dissolution rate of the active ingredient will be independent of its polymorphous form, crystallinity, particle size and specific surface area. Hitherto known pharmaceutical forms with prolonged release of the active ingredient containing a crystalline active ingredient in the pharmaceutical form have the essential disadvantage that, due to the presence of the crystalline active ingredient in several polymorphous modifications, the release rate of the active ingredient depends on the polymorphous modification, the crystal size and thus on the specific surface area of the active ingredient. The dissolution rate of a crystalline substance is not constant and it changes depending on various shapes and size distribution of the crystals of the active ingredient.
PRIOR ART
The use of cellulose ethers of various viscosities and molecular weights in the function of controlling the release rate has been known for a long time. In U.S. Pat. No. 4,259,314 there is described a method for the preparation of a dry pharmaceutical preparation with controlled and sustained release, which is provided by a mixture of hydroxypropylmethylcellulose and hydroxypropylcellulose together with a hygroscopic active ingredient.
N. A. Shaikh, S. E. Abidi and L. H. Block (Drug Development and Industrial Pharmacy, 13 (8), 1345-1369 (1987)) studied the influence of the concentration of ethylcellulose in a pharmaceutical preparation on t
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Kerc Janez
Kofler Bojan
Rebic Ljubomira Barbara
LEK, tovarna farmacevtskih in kemicnih izdelkov, d.d.
Williamson Michael A.
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