Methods of treatment using a gastric retained gabapentin dosage
View Patent ↗A method of treatment for epilepsy and other disease states is described, which comprises delivery of gabapentin in a gastric retained dosage form.
1. An oral dosage form, comprising
an osmotic device comprising a core comprising gabapentin, and a semipermeable membrane surrounding the core, wherein the semipermeable membrane comprises a plasticizer, is permeable to a fluid in an environment of use and is substantially impermeable to unsolubilized gabapentin,
wherein the oral dosage form as formulated is of sufficient size to promote retention in the stomach of a subject in the fed mode for a period of at least about 5 hours,
wherein the dosage form is a tablet comprising about 100 mg to about 4800 mg gabapentin,
wherein the gabapentin is released into the upper gastrointestinal tract over a period of about 5-12 hours at a rate sufficient to achieve a lower maximum plasma concentration (C max ) compared to an equal dose of gabapentin provided by an immediate release dosage form.
2. The dosage form of claim 1 , wherein the dosage form provides bioavailability of gabapentin at a level greater than or equal to 80 % of that provided by an equal dose of gabapentin released by the immediate release dosage form as measured by the plasma AUC inf .
3. The dosage form of claim 1 , wherein the osmotic device comprises an elementary pump.
4. The dosage form of claim 1 , wherein the dosage form comprises about 300 mg or about 600 mg gabapentin.
5. The dosage form of claim 1 , further comprising a second therapeutic agent selected from the group consisting of a hydantoin, an iminostilbene, a valproate, a phenyltriazine, a barbiturate, a deoxybarbiturate, a benzodiazepine, a carbamate, an anticonvulsant other than gabapentin, a tricyclic antidepressant, levadopa, carbidopa, an opioid, lithium, carbamazepine, valproate, trifluoperazine, clonazepam, risperidone, lorazepam, venlafaxine, clozapine, olanzapine, a benzodiazepine, a neuroleptic, a serotonin reuptake inhibitor, buproprion, nefadone, venlaxatine, nefadone, diazepam, oxazepam, a dopaminergic agent, clonazepam, a triptan and ergotamine.
6. The dosage form of claim 1 , wherein the osmotic device comprises a push-pull osmotic device comprising a first osmotic composition and a second osmotic composition housed in a compartment of the push-pull osmotic device.
7. The dosage form of claim 6 , wherein the dosage form provides for bioavailability of gabapentin at a level greater than or equal to 80 % of that provided by an equal dose of gabapentin released by the immediate release dosage form as measured by the plasma AUC inf .
8. The dosage form of claim 6 , wherein the dosage form comprises about 300 mg or about 600 mg gabapentin.
9. The dosage form of claim 6 , further comprising a second therapeutic agent selected from the group consisting of a hydantoin, an iminostilbene, a valproate, a phenyltriazine, a barbiturate, a deoxybarbiturate, a benzodiazepine, a carbamate, an anticonvulsant other than gabapentin, a tricyclic antidepressant, levadopa, carbidopa, an opioid, lithium, carbamazepine, valproate, trifluoperazine, clonazepam, risperidone, lorazepam, venlafaxine, clozapine, olanzapine, a benzodiazepine, a neuroleptic, a serotonin reuptake inhibitor, buproprion, nefadone, venlaxatine, nefadone, diazepam, oxazepam, a dopaminergic agent, clonazepam, a triptan and ergotamine.
10. The dosage form of claim 1 , wherein the osmotic device comprises a macroporous membrane.
11. The dosage form of claim 10 , wherein the dosage form provides for bioavailability of gabapentin at a level greater than or equal to 80 % of that provided by an equal dose of gabapentin released by the immediate release dosage form as measured by the plasma AUC inf .
12. The dosage form of claim 10 , wherein the dosage form comprises about 300 mg or about 600 mg gabapentin.
13. The dosage form of claim 10 , further comprising a second therapeutic agent selected from the group consisting of a hydantoin, an iminostilbene, a valproate, a phenyltriazine, a barbiturate, a deoxybarbiturate, a benzodiazepine, a carbamate, an anticonvulsant other than gabapentin, a tricyclic antidepressant, levadopa, carbidopa, an opioid, lithium, carbamazepine, valproate, trifluoperazine, clonazepam, risperidone, lorazepam, venlafaxine, clozapine, olanzapine, a benzodiazepine, a neuroleptic, a serotonin reuptake inhibitor, buproprion, nefadone, venlaxatine, nefadone, diazepam, oxazepam, a dopaminergic agent, clonazepam, a triptan and ergotamine.
14. The dosage form of claim 1 , wherein the plasticizer is selected from acetylated monoglycerides, dibutyl phthalate, diethyl phthalate, isopropyl phthalate, dimethyl phthalate, dactyl phthalate, dibutyl sebacate, dimethyl sebacate, esters, fatty acids, glycols, oils, glycerin, glycerol, glycerol monostearate, and triacetin.
15. The dosage form of claim 14 , wherein the plasticizer is selected from esters and fatty acids.
16. The dosage form of claim 15 , wherein the ester is selected from the group consisting of acetyl triethyl citrate, acetyl tributyl citrate, citrate ester, dibutyl sebacate, tetraethyl acetate, and triethyl citrate.
17. The dosage form of claim 15 , wherein the fatty acid is a stearic acid.
18. The dosage form of claim 1 , wherein the subject is a human.