Claims for Patent: 10,441,554

Summary for Patent: 10,441,554

Title:	Oral amphetamine composition
Abstract:	In various embodiments, the present invention is directed to oral pharmaceutical compositions. For example, in some embodiments, the present invention is directed to taste-masked compositions. In some embodiments, the taste masked compositions comprise a highly water soluble drug such as amphetamine, e.g., in the form of a salt such as amphetamine sulfate. In various embodiments, the present invention is directed to taste-masked, orally disintegrating compositions.
Inventor(s):	Venkatesh; Gopi M. (Vandalia, OH), Schilling; Michelle (New Carlisle, OH)
Assignee:	ADARE PHARMACEUTICALS, INC. (Lawrenceville, NJ)
Application Number:	16/000,322
Patent Claims:	1. An orally disintegrating pharmaceutical composition comprising: (a) taste-masked drug containing particles comprising: (i) drug-containing core particles comprising a therapeutically effective amount of racemic amphetamine, or a pharmaceutically acceptable salt or ester thereof and at least one excipient; (ii) a first taste-masking membrane comprising ethylcellulose and excluding pharmaceutically acceptable gastrosoluble polymers, wherein the first taste-masking membrane is disposed on the drug-containing core particles and has a membrane thickness of from about 5% to about 10% by wt. of the taste-masked drug containing particle, and (iii) a second taste-masking membrane comprising ethylcellulose and aminoalkyl methacrylate copolymer at a ratio of about 50/50 by wt., wherein the second taste-masking membrane is disposed on the first taste-masking membrane and the second taste-masking membranes has a thickness of from about 15% to about 30% by wt. of the taste-masked drug containing particle; (b) a disintegrant; (c) a sugar alcohol or saccharide, or mixture thereof; and wherein if the orally disintegrating pharmaceutical composition comprises 30 mg of racemic amphetamine sulfate, after administration the orally disintegrating pharmaceutical composition provides one or more of the following: an AUC.sub.inf ranging from about 80% to about 125% of about 400-600 hr*ng/mL; a C.sub.max ranging from about 80% to about 125% of about 25-35 ng/mL; or a T.sub.max ranging from about 80% to about 125% of about 2-4 hrs. 2. The orally disintegrating pharmaceutical composition of claim 1, wherein the therapeutically effective amount of racemic amphetamine, or a pharmaceutically acceptable salt or ester thereof in the drug containing core particles is a dose equivalent to 30 mg of racemic amphetamine sulfate, wherein after administration, the orally disintegrating pharmaceutical composition provides two or more of the following: an AUC.sub.inf ranging from about 80% to about 125% of about 400-600 hr*ng/mL; a C.sub.max ranging from about 80% to about 125% of about 25-35 ng/mL; or a T.sub.max ranging from about 80% to about 125% of about 2-4 hrs. 3. The orally disintegrating pharmaceutical composition of claim 1, wherein the therapeutically effective amount of racemic amphetamine, or a pharmaceutically acceptable salt or ester thereof in the drug containing core particles is a dose equivalent to 30 mg of racemic amphetamine sulfate, wherein after administration, the orally disintegrating pharmaceutical composition provides the following: an AUC.sub.inf ranging from about 80% to about 125% of about 400-600 hr*ng/mL; a C.sub.max ranging from about 80% to about 125% of about 25-35 ng/mL; and a T.sub.max ranging from about 80% to about 125% of about 2-4 hrs. 4. The orally disintegrating pharmaceutical composition of claim 1, wherein the ethylcellulose in the first taste-masking membrane has a viscosity of about 100 cps. 5. The orally disintegrating pharmaceutical composition of claim 1, wherein the ethylcellulose in the second taste-masking membrane has a viscosity of about 10 cps. 6. The orally disintegrating pharmaceutical composition of claim 1, wherein the ethylcellulose in the first taste-masking membrane has a viscosity of about 100 cps, and the ethylcellulose in the second taste-masking membrane has a viscosity of about 10 cps. 7. The orally disintegrating pharmaceutical composition of claim 1, wherein the disintegrant and the sugar alcohol and/or saccharide are present together in the form of rapidly dispersing microgranules. 8. The orally disintegrating pharmaceutical composition of claim 7, wherein the rapidly dispersing microgranules have an average particle size of not more than about 300 .mu.m. 9. The orally disintegrating pharmaceutical composition of claim 8, wherein the disintegrant has an average particle diameter of not more than about 30 .mu.m. 10. The orally disintegrating pharmaceutical composition of claim 8, wherein the sugar alcohol and/or saccharide has an average particle diameter of not more than about 30 .mu.m. 11. The orally disintegrating pharmaceutical composition of claim 1, wherein taste-masked drug containing particles have an average particle size of not more than about 400 .mu.m. 12. The orally disintegrating pharmaceutical composition of claim 1, wherein the excipient in the drug-containing core particles is mannitol, the racemic amphetamine, or a pharmaceutically acceptable salt or ester thereof is racemic amphetamine sulfate, and the drug-containing core particles are an amphetamine sulfate-mannitol granulate. 13. The orally disintegrating pharmaceutical composition of claim 1, wherein the excipient in the drug-containing core particle is a bead, the racemic amphetamine, or a pharmaceutically acceptable salt or ester thereof is racemic amphetamine sulfate, and the drug-containing core particles are an amphetamine sulfate layered bead. 14. The orally disintegrating pharmaceutical composition of claim 1, wherein the therapeutically effective amount of racemic amphetamine, or a pharmaceutically acceptable salt or ester thereof is a dose equivalent to about 30 mg. 15. The orally disintegrating pharmaceutical composition of claim 1, wherein the therapeutically effective amount of racemic amphetamine, or a pharmaceutically acceptable salt or ester thereof in the drug containing core particles is in the range of from about 5 mg to about 40 mg. 16. The orally disintegrating pharmaceutical composition of claim 15, wherein the therapeutically effective amount of racemic amphetamine, or a pharmaceutically acceptable salt or ester thereof in the drug containing core particles is a dose equivalent to about 5 mg of racemic amphetamine sulfate. 17. The orally disintegrating pharmaceutical composition of claim 15, wherein the therapeutically effective amount of racemic amphetamine, or a pharmaceutically acceptable salt or ester thereof in the drug containing core particles is a dose equivalent to about 10 mg of racemic amphetamine sulfate. 18. The orally disintegrating pharmaceutical composition of claim 15, wherein the therapeutically effective amount of racemic amphetamine, or a pharmaceutically acceptable salt or ester thereof in the drug containing core particles is a dose equivalent to about 15 mg of racemic amphetamine sulfate. 19. The orally disintegrating pharmaceutical composition of claim 15, wherein the therapeutically effective amount of racemic amphetamine, or a pharmaceutically acceptable salt or ester thereof in the drug containing core particles is a dose equivalent to about 20 mg of racemic amphetamine sulfate. 20. The orally disintegrating pharmaceutical composition of claim 15, wherein the therapeutically effective amount of racemic amphetamine, or a pharmaceutically acceptable salt or ester thereof in the drug containing core particles is a dose equivalent to about 25 mg of racemic amphetamine sulfate. 21. The orally disintegrating pharmaceutical composition of claim 15, wherein the therapeutically effective amount of racemic amphetamine, or a pharmaceutically acceptable salt or ester thereof in the drug containing core particles is a dose equivalent to about 30 mg of racemic amphetamine sulfate. 22. The orally disintegrating pharmaceutical composition of claim 15, wherein the therapeutically effective amount of racemic amphetamine, or a pharmaceutically acceptable salt or ester thereof in the drug containing core particles is a dose equivalent to about 40 mg of racemic amphetamine sulfate.