Composition comprising a mixture of dextro- and levo-amphetamines complexed with ion-exchange resin particles to form drug resin particles
DCFirst Claim
1. A pharmaceutical composition comprising a mixture of dextro- and levo-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 drug-resin particles that are uncoated 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 dosage forms that provide prolonged therapy. In particular, the invention relates to dosage forms including various pluralities of drug-containing resin particles. In a particular embodiment, the drug dosage form comprises a mixture of dextro- and levo-amphetamines complexed with ion-exchange resin particles to form drug resin particles. The invention also relates to methods of making these dosage forms and methods of treating using these dosage forms.
54 Citations
20 Claims
- 1. A pharmaceutical composition comprising a mixture of dextro- and levo-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 drug-resin particles that are uncoated 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 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 drug-resin particles that are uncoated 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 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 drug-resin particles that are uncoated 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 AUC0-24 of 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 drug-resin particles that are uncoated 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 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 drug-resin particles that are uncoated 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 (dextroamphetamine+levoamphetamine).
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17. 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 drug-resin particles that are uncoated 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 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 drug-resin particles that are uncoated 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 without resin particles under similar exposure to food, said reference composition comprising a mixture of dextroamphetamine sulfate, dextroamphetamine saccharate, amphetamine aspartate, and amphetamine sulfate.
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19. A pharmaceutical composition comprising a mixture of dextro- and levo-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 drug-resin particles that are uncoated 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 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 drug-resin particles that are uncoated 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