Claims for Patent: 6,162,463

Summary for Patent: 6,162,463

Title:	Extended release formulation of diltiazem hydrochloride
Abstract:	An extended release formulation of diltiazem which is suitable for once-daily oral administration comprises a quantity of a quick release preparation of diltiazem or a pharmaceutically active salt thereof, mixed with a quantity of a slow release (or delayed release) preparation of diltiazem or a pharmaceutically active salt thereof. The quick release preparation used obtains a maximal release of diltiazem within approximately 1-2 hours after administration, and then falls toward baseline levels. The delayed release preparation individually shows a maximal release of diltiazem at between approximately 6-8 hours after administration. The formulation containing the two preparation achieves a maximal release of diltiazem approximately within 1-2 hours after administration, and the levels of released diltiazem remain near these maximal levels for approximately another 12 hours after administration, compared to other extended release formulations of diltiazem (referred to herein as slow or delayed release preparations) which achieve maximal release approximately 9 hours after oral administration. The preferred embodiment is a capsule containing the formulation, which, based upon the total quantity of drug in the formulation rather than total weight of the formulation, comprises up to approximately 25 percent by weight of the quick release preparation of diltiazem, and up to 75 percent by weight of the slow (or delayed) release preparation of diltiazem. The present invention has application for combinations of other preparations of quick release and slow or delayed release pharmaceuticals.
Inventor(s):	Lippa; Arnold S. (Hackensack, NJ)
Assignee:
Application Number:	09/067,573
Patent Claims:	1. An extended release pharmaceutical formulation comprising: a. a pharmaceutically active compound or a pharmaceutically active salt thereof in the amount of between 1% to 25% of total weight of the active compound; and b. a quantity of between 75% to 99% of the total weight of the active compound of a preparation of a pharmaceutically active compound or a pharmaceutically active salt thereof wherein the preparation is characterized by a delayed release of the pharmaceutically active compound or the pharmaceutically active salt thereof with a maximum release of the active compound or active salt thereof achieved within approximately 5-8 hours of administration. 2. The controlled release formulation as described in claim 1, wherein the quantity of the pharmaceutically active compound or the pharmaceutically active salt thereof achieves a maximum release of the active compound or active salt thereof within approximately 1-2 hours of administration. 3. The controlled release formulation as described in claim 1, wherein the controlled release formulation maintains the released active compound or active salt thereof at almost the maximum levels over a period of approximately 12 hours after achieving the maximum release. 4. The controlled release formulation as described in claim 3, wherein the controlled release formulation is suitable for once-daily administration. 5. The controlled release formulation as described in claim 3, wherein the formulation is suitable for oral administration. 6. The controlled release formulation as described in claim 5, wherein the release of the active compound or its active salt thereof is measured by determining the concentration of the released active compound or its active salt thereof in the blood plasma. 7. The controlled release formulation as described in claim 5, wherein the pharmaceutically active compound consists of diltiazem, or a pharmaceutically active salt thereof, and the pharmaceutically active compound in the preparation is diltiazem or a pharmaceutically active salt thereof. 8. A capsule comprising an controlled release formulation according to claim 1. 9. A extended release diltiazem formulation, comprising: a. diltiazem or a pharmaceutically active salt thereof in the amount of between 1% to 25% of total weight of the active compound; and b. a quantity of between 75% to 99% of the total weight of the active compound of a preparation of diltiazem or a pharmaceutically active salt thereof wherein the preparation is characterized by a delayed release of the diltiazem or the pharmaceutically active salt thereof with a maximum release of the active compound or active salt thereof achieved within approximately 5-8 hours of administration. 10. The controlled release diltiazem formulation as described in claim 9, wherein the quantity of diltiazem or the pharmaceutically active salt thereof achieves a maximum release of diltiazem or the active salt thereof within approximately 1-2 hours. 11. The controlled release diltiazem formulation as described in claim 9, wherein the controlled release formulation maintains the released diltiazem or pharmaceutically active salt thereof at almost maximum levels over a period of approximately 12 hours after achieving the maximum release. 12. The diltiazem formulation as described in claim 11, wherein the controlled release diltiazem formulation is suitable for once-daily administration. 13. The controlled release diltiazem formulation as described in claim 11, wherein the controlled release diltiazem formulation is suitable for oral administration. 14. The controlled release diltiazem formulation as described in claim 13, wherein the release of diltiazem or its pharmaceutically active salt thereof is characterized by determining the concentration of diltiazem or its pharmaceutically active salt thereof in blood plasma. 15. A capsule comprising an controlled release diltiazem formulation of diltiazem or a pharmaceutically acceptable salt thereof according to claim 9. 16. A method for producing an extended release formulation of diltiazem, comprising: a. obtaining a quantity of diltiazem or a pharmaceutically active salt thereof of between 1% to 25% of total weight of the active compound, the diltiazem or the pharmaceutically active salt thereof achieving a maximum release of diltiazem or the pharmaceutically active salt thereof within approximately 1-2 hours; b. obtaining a quantity of a preparation of diltiazem or a pharmaceutically active salt thereof of between 75% to 99% of the total weight of the active compound, the preparation of diltiazem or the pharmaceutically active salt thereof achieving a maximum release of diltiazem or the pharmaceutically active salt thereof within approximately 5-8 hours; and c. mixing the diltiazem or the pharmaceutically active salt thereof together with the preparation to form the extended release formulation, wherein the extended release formulation is characterized by rapidly releasing diltiazem or its pharmaceutically active salt thereof, the rapid release characterized by obtaining a maximum release of diltiazem or its active salt within approximately 1-2 hours after administration, and wherein the extended release diltiazem formulation is further characterized by its maintaining the released diltiazem or pharmaceutically active salt thereof at almost maximum levels over a period of approximately 12 hours after achieving the maximum release.