Gastric retained gabapentin dosage form

• US 8,192,756 B2
• Filed: 05/19/2011
• Issued: 06/05/2012
• Est. Priority Date: 10/25/2001
• Status: Expired due to Term

• Current Assignee: Almatica Pharma LLC (Alvogen Inc.)
• Original Assignee: Depomed Incorporated (Assertio Holdings, Inc.)
• Inventors: Hou, Sui Yuen Eddie, Berner, Bret, Gusler, Gloria M
• Primary Examiner(s): Wax, Robert A
• Assistant Examiner(s): Tcherkasskaya, Olga V
• Application Number:
  US13/111,575
• Publication Number:
  US 20110256223A1
• Time in Patent Office: 383 Days
• Field of Search: None
• US Class Current: 424/473
• CPC Class Codes: A61K 31/195 having an amino group
• CPC Class Codes: A61K 31/197 the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid carnitine A61K31/205
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/0002 Galenical forms characterised by the drug release technique; Application systems commanded by energy
• CPC Class Codes: A61K 9/0065 Forms with gastric retention, e.g. floating on gastric juice, adhering to gastric mucosa, expanding to prevent passage through the pylorus
• CPC Class Codes: A61K 9/2031 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers
• CPC Class Codes: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/48 Preparations in capsules, e.g. of gelatin, of chocolate A61K9/0004 takes precedence; bite capsules A61K9/0056
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/02 for peripheral neuropathies
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/06 Antimigraine agents
• CPC Class Codes: A61P 25/08 Antiepileptics; Anticonvulsants
• CPC Class Codes: A61P 25/14 for treating abnormal movements, e.g. chorea, dyskinesia
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/24 Antidepressants
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]

Abstract

A method of treatment for epilepsy and other disease states is described, which comprises the delivery of gabapentin in a gastric retained dosage form.

Claims

1. A dosage form, comprising:

comprising from 100 mg to 4800 mg of therapeutically effective amount of gabapentin or pharmaceutically acceptable salt thereof, dispersed in a single matrix

wherein the matrix comprises at least one swellable hydrophilic polymer that swells unrestrained dimensionally by imbibing water to increase its size to promote gastric retention of the dosage form in the stomach in a fed mode,

wherein upon once-daily or twice-daily ingestion of the dosage form gabapentin is released from the matrix over a period of at least five hours wherein at least 40 wt% of the gabapentin is retained in the matrix one hour after administration, and

wherein the gabapentin is released 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, and without loss in bioavailability as measured by the area under the curve (AUC_infinity) as compared to the bioavailability which is achieved from an immediate release dosage form comprising the same dose of gabapentin.

2. The dosage form of claim 1, wherein the time to reach maximum plasma concentration is longer relative to the time to reach maximum plasma concentration from an immediate release dosage form comprising the dose of gabapentin.

3. The dosage form of claim 2, wherein the time to reach maximum plasma concentration is at least 5.6 hours ±

34.9%.

4. The dosage form of claim 1, wherein a maximum plasma concentration (C_max) of at least about 3 μ

g/mL is achieved.

5. The dosage form of claim 1, comprising a dose of gabapentin of between about 300-600 mg.

12. The dosage form of claim 1, further comprising an immediate release coating.

13. The dosage form of claim 12, wherein said coating comprises a second drug.

14. The dosage form of claim 13, wherein said second drug is gabapentin.

6. A method of treating a condition responsive to a therapeutic dose of gabapentin, comprising:

orally administering once-daily or twice daily a dosage form comprising between about 100 mg to about 4800 mg of gabapentin or pharmaceutically acceptable salt thereof, dispersed in a single matrix,

wherein the matrix comprises at least one swellable hydrophilic polymer that swells unrestrained dimensionally by imbibing water to increase its size to promote gastric retention of the dosage form in the stomach in a fed mode,

wherein upon once-daily or twice daily ingestion of the dosage form gabapentin is released from the matrix over a period of at least five hours wherein at least 40 wt% of the gabapentin is retained in the matrix one hour after administration, and

whereby the dosage form releases gabapentin 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, and without loss in bioavailability as measured by the area under the curve (AUC_infinity) as compared to the bioavailability which is achieved from an immediate release dosage form comprising the same dose of gabapentin.

7. The method of claim 6, wherein the time to reach maximum plasma concentration is longer relative to the time to reach maximum plasma concentration from an immediate release dosage form comprising the dose of gabapentin.

8. The method of claim 6, wherein the time to reach maximum plasma concentration is at least 5.6 hours ±

34.9%.

9. The method of claim 6, wherein a maximum plasma concentration (C_max) of at least about 3 μ

g/mL is achieved.

10. The method of claim 6, wherein the condition is pain.

11. The method of claim 6, wherein the condition is neuropathic pain.

15. A dosage form, comprising:

comprising from 100 mg to 4800 mg of therapeutically effective amount of gabapentin or pharmaceutically acceptable salt thereof, dispersed in a single matrix,

wherein the matrix comprises at least one swellable hydrophilic polymer that swells unrestrained dimensionally by imbibing water to increase its size to promote gastric retention of the dosage form in the stomach in a fed mode,

wherein upon once-daily or twice-daily ingestion of the dosage form gabapentin is released from the matrix over a period of at least five hours wherein at least 40 wt% of the gabapentin is retained in the matrix one hour after administration.

16. The dosage form of claim 15, further comprising an immediate release coating.

17. The dosage form of claim 16, wherein said coating comprises a second drug.

18. The dosage form of claim 17, wherein said second drug is gabapentin.