Sustained release ranolazine formulations
AssigneesCV Therapeutics, Inc., Syntex (U.S.A.) Inc.
InventorsAndrew A. Wolff, Fiona Baker, John Langridge
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Abstract
A sustained release ranolazine formulation contains an intimate mixture of ranolazine and a partially neutralized pH-dependent binder to form a film that is mostly insoluble in aqueous media below pH 4.5 and soluble in aqueous media above pH 4.5. The formulation is suitable for twice daily administration of ranolazine and is useful for controlling the rate of dissolution of ranolazine, and to maintain human plasma ranolazine levels at between 550 and 7500 ng base/mL.
Claims33
A pharmaceutical dosage form comprising at least about 50 wt % ranolazine and at least one pH dependent binder that inhibits the release of ranolazine from the sustained release dosage form when the sustained release dosage form is subjected to an aqueous environment having a pH of the stomach and that promotes the release of a therapeutic amount of ranolazine in an aqueous solution having a pH above about 4.5.
A compressed tablet comprising from about 70 to about 80 wt % ranolazine, at least one pH dependent binder selected from methacrylic acid copolymers, hydroxypropyl cellulose phthalate, hydroxypropyl methylcellulose phthalate, cellulose acetate phthalate, polyvinyl acetate, phthalate, polyvinylpyrrolidine phthalate, and mixtures thereof, and at least one pH independent binder wherein the compressed tablet includes from about 350 to about 800 mg ranolazine.
A dosage form for delivering ranolazine to a human, wherein the dosage form comprises at least 50% by weight ranolazine and at least one pharmaceutically acceptable excipient, said dosage form when administered at least once over a 24 hour period provides a peak to trough ranolazine level ratio in plasma that does not exceed 4:1 over the 24 hour period.
A dosage form for delivering ranolazine to a human, wherein the dosage form comprises at least 50% by weight ranolazine and the admixture of at least one pharmaceutically acceptable excipient, said dosage form when administered at least once during a 24 hour period maintains a trough plasma ranolazine level that is not less than about 550 ng base/mL over the 24 hour period.
A dosage form for delivering ranolazine to a patient, wherein the dosage form comprises at least 50% by weight ranolazine and the admixture of at least one pharmaceutically acceptable excipient, said dosage form when administered periodically over a 24 hour period maintains plasma ranolazine levels close to minimal effective levels without peak fluctuations.
A method for preparing a sustained release ranolazine dosage form comprising the steps of
- (a) intimately admixing ranolazine with at least one pharmaceutically acceptable excipient;
- (b) granulating the result of step (a) with an aqueous solution of a strong base;
- (c) drying and screening the granules from step (b);
- (d) blending the granules from step (c) with lubricants or tabletting aids;
- (e) compressing the granules from step (d) into a tablet;
- and optionally
- (f) coating the tablets from step (e).
A dosage form for delivering ranolazine to a human, wherein the dosage form comprises at least 50% by weight ranolazine and the admixture of at least one pharmaceutically acceptable excipient, said dosage form when administered at least once during a 24 hour period maintains a trough plasma ranolazine level that is not less than about 850 ng base/mL over the 24 hour period.
A dosage form for delivering ranolazine to a patient, wherein the dosage form comprises at least 50% by weight ranolazine and the admixture of at least one pharmaceutically acceptable excipient, said dosage form when administered at least once during a 24 hour period maintains a peak plasma ranolazine level that is not more than about 7500 ng base/mL over the 24 hour period.
A dosage form for delivering ranolazine to a patient, wherein the dosage form comprises at least 50% by weight ranolazine and the admixture of at least one pharmaceutically acceptable excipient, said dosage form when administered at least once during a 24 hour period maintains a peak plasma ranolazine level that is not more than about 4000 ng base/mL over the 24 hour period.
A dosage form for delivering ranolazine to a patient, wherein the dosage form provides a therapeutic advantage of minimizing variations in ranolazine plasma concentration over a 24 hour period.
Dependencies are inferred from the claim text.