Oral amphetamine composition
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.
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 inf ranging from about 80% to about 125% of about 400-600 hr*ng/mL;
a C max ranging from about 80% to about 125% of about 25-35 ng/mL; or
a T 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 inf ranging from about 80% to about 125% of about 400-600 hr*ng/mL;
a C max ranging from about 80% to about 125% of about 25-35 ng/mL; or
a T 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 inf ranging from about 80% to about 125% of about 400-600 hr*ng/mL;
a C max ranging from about 80% to about 125% of about 25-35 ng/mL; and
a T 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 μm.
9. The orally disintegrating pharmaceutical composition of claim 8 , wherein the disintegrant has an average particle diameter of not more than about 30 μm.
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 μm.
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 μm.
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.