Sustained release formulations for 24 hour release of metroprolol
AssigneeEdward Mendell Co., Inc.
InventorsAnand R. Baichwal, John N. Staniforth
Life of this patent
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Abstract
A sustained release oral solid dosage form of metoprolol pharmaceutical formulation includes a sustained release excipient including a gelling agent, an inert pharmaceutical diluent, a cationic cross-linking agent, and metoprolol provides release of metoprolol for at least about 24 hours. In certain embodiments, the sustained release formulation further includes a hydrophobic material.
Claims34
A tablet for the sustained release of metoprolol or a salt thereof, comprising:
- metoprolol or a pharmaceutically acceptable salt thereof in an amount necessary to render a therapeutic effect in a human patient;
- a sustained release excipient comprising a heteropolysaccharide gum and a homopolysaccharide gum capable of crosslinking said heteropolysaccharide gum when exposed to an environmental fluid;
- an inert pharmaceutical diluent selected from the group consisting of monosaccharide, a disaccharide, a polyhydric alcohol, and mixtures thereof;
- and a pharmaceutically acceptable cationic cross-linking agent selected from the group consisting of alkali metal and alkaline earth metal sulfates, chlorides, borates, bromides, citrates, acetates, lactates and mixtures thereof, and capable of crosslinking with said gums and increasing the gel strength of said gums when the dosage form is exposed to an environmental fluid;
- the ratio of metoprolol to said gums being from about 1:1 to about 1:5, said dosage form providing a sustained release of metoprolol for at least about 24 hours when exposed to an environmental fluid.
A method of preparing a 24 hour formulation of metoprolol, comprising:
- preparing a sustained release excipient comprising a heteropolysaccharide gum;
- a homopolysaccharide gum capable of cross-linking said heteropolysaccharide gum when exposed to an environmental fluid;
- a cationic crosslinking agent selected from the group consisting of alkali metal and alkaline earth metal sulfates, chlorides, borates, bromides, nitrates, acetates, lactate and mixtures thereof and capable of crosslinking with said gums agent to increase the gel strength when said gums are exposed to an environmental fluid, and an inert pharmaceutical diluent;
- combining said sustained release excipient with metoprolol or a pharmaceutically acceptable salt to provide a drug:gum ratio from about 1::1 to about 1:5;
- and
- tableting the resultant mixture such that each tablet includes a dose of metoprolol sufficient to provide a therapeutic effect for at least about 24 hours.
The method of 13, further comprising wet granulating said heteropolysaccharide gum, said homopolysaccharide gum, said cationic cross-linking agent, and said inert diluent prior to incorporating said metoprolol.
The method of 13, further comprising adding a hydrophobic material to said mixture of said sustained release excipient and said metoprolol prior to tabletting in an amount effective to slow the hydration of said gums when exposed to an environmental fluid.
The method of 15, further comprising wet granulating said mixture of sustained release excipient, said metoprolol, and said hydrophobic material prior to tableting.
A method of treating a patient with metoprolol, comprising,
- preparing a sustained release excipient comprising a heteropolysaccharide gum;
- a homopolysaccharide gum capable of cross-linking said heteropolysaccharide gum when exposed to an environmental fluid;
- a cationic crosslinking agent selected from the group consisting of alkali metal alkaline earth metal sulfates, chlorides, borates, bromides, citrates, acetates, lactates and mixtures thereof;
- and capable of crosslinking with said gums agent to increase the gel strength when said gums are exposed to an environmental fluid, and an inert pharmaceutical diluent;
- combining said sustained release excipient with metoprolol or a pharmaceutically acceptable salt to provide a drug:gum ratio from about 1:1 to about 1:5;
- tableting the resultant mixture such that a each tablet includes a dose of metoprolol sufficient to provide a therapeutic effect for about 24 hours or more, and
- administering said tablets to a patient.
A tablet for the sustained release of metoprolol or a salt thereof, comprising:
- metoprolol or a pharmaceutically acceptable salt thereof in an amount necessary to render a therapeutic effect in a human patient for about 24 hours;
- from about 30% to about 60% gum matrix comprising a xanthan gum and locust bean gum in a ratio from about 1:3 to about 3:1;
- from about 1 to about 20% by weight of a pharmaceutically acceptable cationic cross-linking agent selected from the group consisting of alkali metal and alkaline earth metal sulfates, chlorides, borates, bromides, citrates, acetates, lactate and mixtures thereof and capable of crosslinking with said gums and increasing the gel strength of said gums when the dosage form is exposed to an environmental fluid;
- and
- an inert pharmaceutical diluent selected from the group consisting of monosaccharide, a disaccharide, a polyhydric alcohol, and mixtures thereof.
Dependencies are inferred from the claim text.