Gastric retentive oral dosage form with restricted drug release in the lower gastrointestinal tract

• US 7,976,870 B2
• Filed: 01/29/2004
• Issued: 07/12/2011
• Est. Priority Date: 10/25/2001
• Status: Expired due to Fees

• Current Assignee: Assertio Therapeutics, Inc. (Assertio Holdings, Inc.)
• Original Assignee: Depomed Incorporated (Assertio Holdings, Inc.)
• Inventors: Shell, John W., Berner, Bret, Louie-Helm, Jenny
• Primary Examiner(s): Richter; Johann R
• Assistant Examiner(s): Holt; Andriae M
• Application Number:
  US10/769,574
• Publication Number:
  US 20040185105A1
• Time in Patent Office: 2,721 Days
• Field of Search: 424/400, 424/469, 424/464, 424/468, 424/486
• US Class Current: 424/468
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• 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 31/496 Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• CPC Class Codes: A61K 31/65 Tetracyclines
• 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 9/20 Pills, tablets, discs, rods A61K9/0004, A61K9/0007, A61K9/0056, A61K9/0065 take precedence; for reconstitution of a drink A61K9/0095
• 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: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/06 for tuberculosis
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

Controlled release oral dosage forms are provided for the continuous, sustained administration of a pharmacologically active agent to the upper gastrointestinal tract of a patient in whom the fed mode as been induced. The majority of the agent is delivered, on an extended release basis, to the stomach, duodenum and upper regions of the small intestine, with drug delivery in the lower gastrointestinal tract and colon substantially restricted. The dosage form comprises a matrix of a biocompatible, hydrophilic, erodible polymer with an active agent incorporated therein, wherein the polymer is one that both swells in the presence of water and gradually erodes over a time period of hours, with swelling and erosion commencing upon contact with gastric fluid, and drug release rate primarily controlled by erosion rate.

Claims

1. A method for delivering a pharmacologically active agent, the method comprising:

orally administering to a patient in a fed mode a matrix/active agent tablet dosage form comprised of a polymer matrix and the pharmacologically active agent dispersed in said polymer matrix, said polymer matrix comprised of a biocompatible, hydrophilic polymer which

(a) upon imbibition of water swells unrestrained dimensionally to a size effective to promote gastric retention for a time period of about 4 to 9 hours, and

(b) maintains its size for the time period before it is diminished by erosion,

wherein at least 75 wt. % of the active agent in the dosage form is released by erosion of the polymer matrix within the time period.

2. The method of claim 1, wherein at least 85 wt. % of the active agent in the dosage form is released within the time period.

3. The method of claim 1, wherein the dosage form is characterized by an erosion rate (ER) to dissolution rate (DR) ratio of approximately 1.1:

1 to 5;

1, wherein ER is the rate of active agent release in an aqueous medium measured using an in vitro disintegration test, and DR is the rate of active agent release in an aqueous medium measured using an in vitro dissolution test.

4. The method of claim 1, wherein the dosage form is characterized by an ER to DR ratio of approximately 1.2:

1 to approximately 3;

1.

5. The method of claim 4, wherein the dosage form is characterized by an ER to DR ratio of approximately 1.3:

1 to approximately 2;

1.

6. The method of claim 5, wherein the dosage form is characterized by an ER to DR ratio of approximately 1.5:

1 to approximately 2;

1.

7. The method of claim 1, wherein the matrix-active agent tablet comprises a therapeutically effective amount of the pharmacologically active agent.

8. The method of claim 7, wherein the therapeutically effective amount of the active agent in the dosage form is in a range of about 0.01% to 80% by volume.

9. The method of claim 8, wherein the therapeutically effective amount of the active agent in the dosage form is in a range of about 60% to about 80% of the dosage form by volume.

10. The method of claim 9, wherein the therapeutically effective amount of the active agent in the dosage form is approximately 60% by volume.

11. The method of claim 1, wherein said active agent possesses an aqueous solubility that decreases with increasing pH.

12. The method of claim 11, wherein following administering of said dosage form and gastric retention thereof, the dosage form passes into the lower gastrointestinal tract, whereby active agent remaining in the dosage form is insoluble and unavailable for absorption.

13. The method of claim 1, wherein the active agent is an antibiotic.

14. The method of claim 13, wherein the active agent is selected from the group consisting of ciprofloxacin, minocycline, and acid addition salts thereof.

15. The method of claim 14, wherein the active agent is ciprofloxacin.

16. The method of claim 14, wherein the active agent is ciprofloxacin hydrochloride.

17. The method of claim 14, wherein the active agent is minocycline.

18. The method of claim 14, wherein the active agent is minocycline hydrochloride.

19. The method of claim 1, wherein the active agent is selected from the group consisting of furosemide, gabapentin, losartan, and budesonide.

20. The method of claim 1, wherein the active agent is gabapentin.

21. A method for treating a human patient suffering from a bacterial infection that is responsive to the oral administration of ciprofloxacin, comprising orally administering to the subject in a fed mode a therapeutically effective amount of the dosage form of claim 1.

22. The method of claim 21, wherein the dosage form is administered once daily.

23. The method of claim 21, wherein the bacterial infection is infection with mycobacterium avium complex, Pseudomonas, Shigella, Salmonella, toxigenic E. coli, Campylobacter, Enterobacter, or Bacillus anthracis.