Pharmaceutical composition comprising amphetamines complexed with ion-exchange resin particles
DCFirst Claim
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1. A pharmaceutical composition comprising amphetamines complexed with ion-exchange resin particles to form drug-resin particles, wherein 30 to 50% by weight of said amphetamines are present in a first plurality of immediate release drug-resin particles and 50 to 70% by weight of said amphetamines are present in a second plurality of drug-resin particles that are coated with a delayed release coating.
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Abstract
The invention relates to a pharmaceutical composition comprising amphetamines complexed with ion-exchanged resin particles to form drug-resin particles. The composition provides for prolonged therapy.
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Citations
21 Claims
- 1. A pharmaceutical composition comprising amphetamines complexed with ion-exchange resin particles to form drug-resin particles, wherein 30 to 50% by weight of said amphetamines are present in a first plurality of immediate release drug-resin particles and 50 to 70% by weight of said amphetamines are present in a second plurality of drug-resin particles that are coated with a delayed release coating.
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12. A pharmaceutical composition comprising amphetamines complexed with ion-exchange resin particles to form drug resin particles, wherein said composition comprises a first plurality of immediate release drug-resin particles and a second plurality of drug-resin particles that are coated with a delayed release coating, wherein a mammal receiving said composition, in the presence of ethanol, is exposed to a reduced amount of amphetamines compared to when said mammal receives a composition without resin particles particles in the presence of ethanol, said composition comprising a mixture of dextroamphetamine sulfate, dextroamphetamine saccharate, amphetamine aspartate, and amphetamine sulfate.
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14. A pharmaceutical composition comprising a mixture of dextro- and levo-amphetamines complexed with ion-exchange resin particles to form drug resin particles, wherein said composition comprises a first plurality of immediate release drug-resin particles and a second plurality of drug-resin particles that are coated with a delayed release coating, wherein said composition is an orally disintegrating tablet and is effective to provide a mean plasma concentration profile in human ADHD patients which has the following AUC and Cmax values for a 30 mg total dose, or respective AUC and Cmax values directly proportional thereto for a total dose other than 30 mg:
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(a) an AUC0-4 of 85.8 ng hr/mL −
20% /+25% and a Cmax of 44.5 ng/mL −
20% /+25% for dextroamphetamine and/or an AUC0-4 of 26.3 ng hr/mL −
20% /+25% and a Cmax of 14.2 ng/mL −
20% /+25% for levoamphetamine;(b) an AUC0-5 of 126.3 ng hr/mL −
20% /+25% and a Cmax of 44.5 ng/mL −
20% /+25% for dextroamphetamine and/or an AUC0-5 of 39.1 ng hr/mL −
20% /+25% and a Cmax of 14.2 ng/mL−
20% /+25% for levoamphetamine;(c) an AUC4-12 of 291 ng hr/mL −
20% /+25% and a Cmax of 44.5 ng/mL −
20% /+25% for dextroamphetamine and/or an AUC4-12 of 95.1 ng hr/mL −
20% /+25% and a Cmax of 14.2 ng/mL −
20% /+25% for levoamphetamine;(d) an AUC5-12 of 250.5 ng hr/mL −
20% /+25% and a Cmax of 44.5 ng/mL −
20% /+25% for dextroamphetamine and/or an AUC5-12 of 82.3 ng hr/mL −
20% /+25% and a Cmax of 14.2 ng/mL −
20% /+25% for levoamphetamine; and
/or(e) an AUC0-24 of 613.3 ng hr/mL −
20% /+25% and a Cmax of 44.5 ng/mL −
20% /+25% for dextroamphetamine and/or an AUC0-24of 204.9 ng hr/mL −
20% /+25% and a Cmax of 14.2 ng/mL −
20% /+25% for levoamphetamine.
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15. A pharmaceutical composition comprising a mixture of dextro- and levo-amphetamines complexed with ion-exchange resin particles to form drug resin particles, wherein said composition comprises a first plurality of immediate release drug-resin particles and a second plurality of drug-resin particles that are coated with a delayed release coating, wherein said composition is a liquid suspension and is effective to provide a mean plasma concentration profile in human ADHD patients which has the following AUC and Cmax values for a 30 mg total dose, or respective AUC and Cmax values directly proportional thereto for a total dose other than 30 mg:
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(a) an AUC0-4 of 104.7 ng hr/mL −
20% /+25% and a Cmax of 46.3 ng/mL −
20% /+25% for dextroamphetamine and/or an AUC0-4 of 31.8 ng hr/mL −
20% /+25% and a Cmax of 14.6 ng/mL −
20% /+25% for levoamphetamine;(b) an AUC0-5 of 148.6 ng hr/mL −
20% /+25% and a Cmax of 46.3 ng/mL −
20% /+25% for dextroamphetamine and/or an AUC0-5 of 45.7 ng hr/mL −
20% /+25% and a Cmax of 14.6 ng/mL −
20% /+25% for levoamphetamine; and
/or(c) an AUC4-12 , of 300.3 ng hr/mL −
20% /+25% and a Cmax of 46.3 ng/mL −
20% /+25% for dextroamphetamine and/or an AUC4-12 , of 96.8 ng hr/mL −
20% /+25% and a Cmax of 14.6 ng/mL −
20% /+25% for levoamphetamine.
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16. A pharmaceutical composition comprising amphetamines complexed with ion-exchange resin particles to form drug resin particles, wherein said composition comprises a first plurality of immediate release drug-resin particles and a second plurality of drug-resin particles that are coated with a delayed release coating, wherein said composition, when containing about a total amphetamine dose of 30 mg, will produce in a human, a mean plasma concentration versus time curve (ng/ml versus hours) having an area under the curve (AUC0-∞
- ) of about 1140 to about 1240 for total amphetamines.
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17. A pharmaceutical composition comprising dextro-amphetamines, levo-amphetamines, or a racemic mixture thereof complexed with ion-exchange resin particles to form drug resin particles, wherein said composition comprises a first plurality of immediate release drug-resin particles and a second plurality of drug-resin particles that are coated with a delayed release coating, wherein one or more in vivo pharmacokinetic parameters of the composition selected from the group consisting of Cmax, AUC0-5, AUC5-12, AUC5-24, AUC5-t, AUC0-12, AUC0-24, AUC0-t,and AUC0-∞
- have a 90% confidence interval with upper and lower bounds within a range from 90%-115% of the value of the same parameter(s) for a bioequivalent reference composition.
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18. A pharmaceutical composition comprising amphetamines complexed with ion-exchange resin particles to form drug resin particles, wherein said composition comprises a first plurality of immediate release drug-resin particles and a second plurality of drug-resin particles that are coated with a delayed release coating, wherein said composition is a liquid suspension and a human receiving said composition substantially contemporaneously with food is exposed to an increased amount of amphetamines in the first 4 hours compared to a human receiving a reference composition comprising a mixture of dextroamphetamine sulfate, dextroamphetamine saccharate, amphetamine aspartate, and amphetamine sulfate.
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19. A pharmaceutical composition comprising amphetamines complexed with ion-exchange resin particles to form drug resin particles, wherein about 50% by weight of said amphetamines are present in a first plurality of immediate release drug-resin particles and about 50% by weight of said amphetamines are present in a second plurality of drug-resin particles that are coated with a delayed release coating.
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20. A pharmaceutical composition comprising amphetamines complexed with ion-exchange resin particles to form drug resin particles, wherein said composition comprises a first plurality of immediate release drug-resin particles and a second plurality of drug-resin particles that are coated with a delayed release coating and wherein said composition has an in vivo fasted serum profile with a first and second peak wherein said first peak occurs between 1 and 3 hours after ingestion of the composition and said second peak occurs between 4 and 7 hours after ingestion and is the Cmax.
Specification