Controlled Absorption of Statins in the Intestine
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Abstract
The present invention provides a controlled absorption formulation in which modified release of active ingredient preferentially occurs in the lower gastrointestinal tract, including the colon. The formulation supports a significantly higher bioavailability of the active ingredient into the body of the subject than can be achieved from the currently used conventional formulation, such that therapeutically significant plasma levels of statin are maintained for an extended period after administration. The formulation preferably features a core over which an outer coating is layered. The core is optionally and preferentially in the form of a tablet.
31 Citations
219 Claims
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1-180. -180. (canceled)
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181. A delayed onset slow release formulation for a statin and/or active forms of the statin, comprising:
- a slowly disintegrating core comprising at least one statin, a filler and a release controlling agent, wherein the release controlling agent is present in a range of from about 5% to about 20% weight per weight relative to the total weight of the core, and a rate-controlling outer coating over the core, the rate-controlling outer coating selected from the group consisting of;
i) an outer coating featuring a mixture of cellulosic water insoluble polymers; ii) an outer coating featuring a combination of a water insoluble polymer and a water soluble polymer; iii) an outer coating featuring an enteric polymer coating; iv) an outer coating featuring a polymer disintegrating at pH values above about pH 5; v) an outer coating featuring a cellulosic polymer that is applied as a dry coating, the polymer forming a hydrogel; vi) an outer coating featuring water insoluble hydrophilic particles embedded in a water insoluble flexible polymer, wherein the statin and/or active forms of the statin are released through diffusion through the water insoluble hydrophilic particles; and vii) an outer coating featuring a dry coating or an enteric coating, with the proviso that the core does not comprise a disintegrating agent. - View Dependent Claims (182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 201, 209, 211, 213)
- a slowly disintegrating core comprising at least one statin, a filler and a release controlling agent, wherein the release controlling agent is present in a range of from about 5% to about 20% weight per weight relative to the total weight of the core, and a rate-controlling outer coating over the core, the rate-controlling outer coating selected from the group consisting of;
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196. A delayed onset controlled release formulation for providing an increased bioavailability as measured by AUC of a statin and/or active forms of the statin, relative to that resulting from the administration of an equivalent dose of the conventional immediate release formulations, comprising:
- a slowly disintegrating core comprising at least one statin and at least one release controlling agent and a rate-controlling outer coating over the core, providing controlled release.
- View Dependent Claims (197, 198, 199, 200, 202, 203, 204, 205, 207, 208, 210, 212, 214, 216, 217)
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215. A method for providing enhanced bioavailability of a statin or pharmaceutically acceptable salts or esters thereof or its related metabolite in a subject, or for providing an increased amount of a statin or a pharmaceutically acceptable salt or ester thereof, relative to that resulting from the administration of an equivalent dose of the conventional immediate release formulations, comprising:
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administering orally to the subject a delayed onset controlled release formulation comprising a core and an outer coating that surrounds the core; the core comprising a statin, or a pharmaceutically acceptable salt thereof and at least one release controlling agent, and the coating characterized by at least one of a. pH dependent coating film, preferably an enteric coating b. a combination of at least one water soluble polymer and at least one water insoluble polymer c. a combination of at least one swellable polymer and at least one water insoluble polymer d. a combination of at least a water soluble pore forming agent and at least one water insoluble polymer e. at least one swellable gel forming polymer f. at least one erodible polymer g. a combination of at least one pH dependent polymer and at least one water insoluble polymer h. a two-layer coating comprising a rupturable outer layer and swellable inner layer wherein the in vivo blood plasma concentration of the statin is substantially zero for at least about two hours after oral administration.
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218. A method for providing enhanced bioavailability of statin and/or a pharmaceutically acceptable salts and/or esters thereof and/or its related metabolite in a subject, comprising:
- administering orally to the subject a controlled release formulation excluding delayed burst release and delayed immediate or fast release characterized in that the in vivo blood plasma concentration of the statin is substantially zero for at least about one hour after oral administration.
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219. A controlled release method for providing an increased amount of a statin and/or active forms of the statin circulating in the blood of a subject, relative to that resulting from the administration of an equivalent dose of a conventional immediate release formulation to the subject, wherein the method excludes delayed burst release and delayed immediate or fast release.
Specification