Oral pulsed dose drug delivery system

Abstract

A multiple pulsed dose drug delivery system for pharmaceutically active amphetamine salts, comprising an immediate-release component and an enteric delayed-release component wherein (1) the enteric release coating has a defined minimum thickness and/or (2) there is a protective layer between the pharmaceutically active amphetamine salt and the enteric release coating and/or (3) there is a protective layer over the enteric release coating. The product can be composed of either one of a number of beads in a dosage form, including either capsule, tablet, or sachet method for administering the beads.

1. A pharmaceutical composition for delivery of one or more pharmaceutically active amphetamine salts, comprising:
 (a) one or more pharmaceutically active amphetamine salts covered with an immediate release coating; and  
 (b) one or more pharmaceutically active amphetamine salts that are covered with an enteric release coating that provides for delayed pulsed enteric release, wherein said enteric release coating releases essentially all of said one or more pharmaceutically active amphetamine salts coated with said enteric coating within about 60 minutes after initiation of said delayed pulsed enteric release release;  
 wherein the pharmaceutically active amphetamine salts in (a) and (b) comprise mixed amphetamine salts. 
 
     
     
       2. The composition of  claim 1  A pharmaceutical composition for delivery of one or more pharmaceutically active amphetamine salts, comprising:
 (a) one or more pharmaceutically active amphetamine salts covered with an immediate release coating; and  
 (b) one or more pharmaceutically active amphetamine salts that are covered with an enteric release coating that provides for delayed pulsed enteric release, wherein said enteric release coating releases essentially all of said one or more pharmaceutically active amphetamine salts coated with said enteric coating within about  60  minutes after initiation of said delayed pulsed enteric release; wherein said enteric release coating has a thickness of at least 25μ.  
 
     
     
       3. The pharmaceutical composition of  claim 1  wherein the one or more pharmaceutically active amphetamine salts are coated onto a core. 
     
     
       4. The pharmaceutical composition of  claim 1  wherein the one or more pharmaceutically active amphetamine salts are incorporated into a core. 
     
     
       5. The pharmaceutical composition of  claim 1  A pharmaceutical composition for delivery of one or more pharmaceutically active amphetamine salts, comprising:
 (a) one or more pharmaceutically active amphetamine salts covered with an immediate release coating; and  
 ( b )  one or more pharmaceutically active amphetamine salts that are covered with an enteric release coating that provides for delayed pulsed enteric release, wherein said enteric release coating releases essentially all of said one or more pharmaceutically active amphetamine salts coated with said enteric coating within about  60  minutes after initiation of said delayed pulsed enteric release;  wherein the one or more pharmaceutically active amphetamine salts covered with an immediate release coating and the one or more pharmaceutically active amphetamine salts covered with an enteric release coating are present on a single core.  
 
     
     
       6. The pharmaceutical composition of  claim 1  wherein the one or more pharmaceutically active amphetamine salts covered with an immediate release coating and the one or more pharmaceutically active amphetamine salts covered with an enteric release coating are present on different cores. 
     
     
       7. The composition of  claim 1  wherein said enteric release coating is a non-pH dependent enteric release coating. 
     
     
       8. A pharmaceutical composition for delivery of at least one amphetamine salt, comprising:
 (a) at least one pharmaceutically active amphetamine salt covered with an immediate release coating; and  
 (b) at least one pharmaceutically active amphetamine salt covered with an enteric release coating, said component (a) providing for an immediate release of amphetamine salt to provide a first blood level of amphetamine salt and component (b) providing a delayed pulse enteric release of amphetamine salt that increases the blood level of amphetamine salt to a second level that is greater than the first level provided by component (a), wherein said enteric release coating releases essentially all of said one or more pharmaceutically active amphetamine salts coated with said enteric coating within about 60 minutes after initiation of said delayed pulsed enteric release;  
 wherein the pharmaceutically active amphetamine salts comprise mixed amphetamine salts in (a) and (b) comprise mixed amphetamine salts.  
 
     
     
       9. The pharmaceutical composition of  claim 8  wherein the one or more pharmaceutically active amphetamine salts are coated onto a core. 
     
     
       10. The pharmaceutical composition of  claim 8  wherein the one or more pharmaceutically active amphetamine salts are incorporated into a core. 
     
     
       11. The pharmaceutical composition of  claim 8  A pharmaceutical composition for delivery of at least one amphetamine salt, comprising:
 (a) at least one pharmaceutically active amphetamine salt covered with an immediate release coating; and  
 (b) at least one pharmaceutically active amphetamine salt covered with an enteric release coating, said component (a) providing for an immediate release of amphetamine salt to provide a first blood level of amphetamine salt and component (b) providing a delayed pulse enteric release of amphetamine salt that increases the blood level of amphetamine salt to a second level that is greater than the first level provided by component (a), wherein said enteric release coating releases essentially all of said one or more pharmaceutically active amphetamine salts coated with said enteric coating within about  60  minutes after initiation of said delayed pulsed enteric release; and wherein the one or more pharmaceutically active amphetamine salts covered with an immediate release coating and the one or more pharmaceutically active amphetamine salts covered with an enteric release coating are present on a single core.  
 
     
     
       12. The pharmaceutical composition of  claim 8  wherein the one or more pharmaceutically active amphetamine salts covered with an immediate release coating and the one or more pharmaceutically active amphetamine salts covered with an enteric release coating are present on different cores. 
     
     
       13. A pharmaceutical composition for delivering one or more pharmaceutically active amphetamine salts comprising:
 (a) one or more pharmaceutically active amphetamine salts covered with an immediate release coating;  
 (b) one or more pharmaceutically active amphetamine salts that are covered with an enteric release coating that provides for delayed pulsed enteric release, wherein said enteric release coating releases essentially all of said one or more pharmaceutically active amphetamine salts coated with said enteric coating within about 60 minutes after initiation of said delayed pulsed enteric release; and  
 (c) a protective layer over the enteric release coating.  
 
     
     
       14. The pharmaceutical composition of  claim 13  wherein the one or more pharmaceutically active amphetamine salts are coated onto a core. 
     
     
       15. The pharmaceutical composition of  claim 13  wherein the one or more pharmaceutically active amphetamine salts are incorporated into a core. 
     
     
       16. The pharmaceutical composition of  claim 13  wherein the one or more pharmaceutically active amphetamine salts covered with an immediate release coating and the one or more pharmaceutically active amphetamine salts covered with an enteric release coating are present on a single core. 
     
     
       17. The pharmaceutical composition of  claim 13  wherein the one or more pharmaceutically active amphetamine salts covered with an immediate release coating and the one or more pharmaceutically active amphetamine salts covered with an enteric release coating are present On  on different cores. 
     
     
       18. A pharmaceutical composition for delivery of one or more pharmaceutically active amphetamine salts comprising:
 (a) one or more pharmaceutically active amphetamine salts covered with an immediate release coating;  
 (b) one or more pharmaceutically active amphetamine salts that are covered with an enteric release coating that provides for delayed pulsed enteric release, wherein said enteric release coating releases said one or more pharmaceutically active amphetamine salts coated with said enteric coating within about 60 minutes after initiation of said delayed pulsed enteric release; and  
 (c) a protective layer between the at least one pharmaceutically active amphetamine salt and the enteric release coating.  
 
     
     
       19. The pharmaceutical composition of  claim 18  wherein The delayed pulsed release is from 4 to 6 hours after administration of the pharmaceutical composition. 
     
     
       20. The pharmaceutical composition of  claim 18  wherein the delayed pulse enteric release, releases the amphetamine salt in about 30 to 60 minutes after initiation of the release. 
     
     
       21. The pharmaceutical composition of  claim 18  wherein the one or more pharmaceutically active amphetamine salts are coated onto a core. 
     
     
       22. The pharmaceutical composition of  claim 18  wherein the one or more pharmaceutically active amphetamine salts are incorporated into a core. 
     
     
       23. The pharmaceutical composition of  claim 18  wherein the one or more pharmaceutically active amphetamine salts covered with an immediate release coating and the one or more pharmaceutically active amphetamine salts covered with an enteric release coating are present on a single core. 
     
     
       24. The pharmaceutical composition of  claim 18  wherein the one or more pharmaceutically active amphetamine salts covered with an immediate release coating and the one or more pharmaceutically active amphetamine salts covered with an enteric release coating are present on different cores. 
     
     
       25. The pharmaceutical composition of any one of claims  2 ,  13  or  18  to  20  wherein the pharmaceutically active amphetamine salt in (a) and (b) comprises mixed amphetamine salts.