Tablet shapes to enhance gastric retention of swellable controlled-release oral dosage forms

• US 6,488,962 B1
• Filed: 06/20/2000
• Issued: 12/03/2002
• Est. Priority Date: 06/20/2000
• Status: Expired due to Term

• Current Assignee: Assertio Therapeutics, Inc. (Assertio Holdings, Inc.)
• Original Assignee: Depomed Incorporated (Assertio Holdings, Inc.)
• Inventors: Berner, Bret, Louie-Helm, Jenny
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): Joynes, Robert M.
• Application Number:
  US09/598,061
• Time in Patent Office: 896 Days
• Field of Search: 424/484, 424/473, 424/457, 424/464, 424/468, 424/469
• US Class Current: 424/484
• 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 9/2072 characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms A61K9/0004, A61K9/0056, A61K9/0065 take precedence

Abstract

The retention of oral drug dosage forms in the stomach is improved by using swellable dosage forms that are shaped in a manner that will prevent them from inadvertently passing through the pylorus as a result of being in a particular orientation. The planar projection of the shape is one that has two orthogonal axes of different lengths, the longer being short enough to permit easy swallowing prior to swelling while the shorter is long enough within one-half hour of swelling to prevent passage through the pylorus.

Claims

1. A controlled-release oral drug dosage form for releasing a drug into at least a portion of a region defined by the stomach and the upper gastrointestinal tract, said dosage form comprising a solid monolithic matrix with said drug contained therein, said matrix being non-circular in shape and having first and second orthogonal axes of unequal length, said matrix being one that swells in an unrestricted manner along both such axes upon imbibition of water, the longer such axis having a maximum length of 3.0 cm when said matrix is unswollen, and the shorter such axis achieving a minimum length of 1.2 cm within one hour of immersion of said dosage form in water and wherein said matrix has a shape which when projected onto a plane, is either an oval or a parallelogram.

2. A controlled-release oral drug dosage form in accordance with claim 1 in which said shorter axis achieves a minimum length of 1.2 cm within thirty minutes of immersion of said dosage form in water.

3. A controlled-release oral drug dosage form in accordance with claim 1 in which said shorter axis achieves a minimum length of 1.3 cm within one hour of immersion of said dosage form in water.

4. A controlled-release oral drug dosage form in accordance with claim 1 in which said shorter axis achieves a minimum length of 1.3 cm within thirty minutes of immersion of said dosage form in water.

5. A controlled-release oral drug dosage form in accordance with claim 1 in which said shorter axis ha s a length of 0.7 cm to 1.5 cm when said matrix is unswollen.

6. A controlled-release oral drug dosage formn in accordance with claim 1 in Which said shorter axis has a length of 0.75 cm to 1.2 cm when said matrix is unswollen.

7. A controlled-release oral drug dosage form in accordance with claim 1 in which said shorter axis has a length of 0.8 cm to 1.0 cm when said matrix is unswollen.

9. A controlled-release oral drug dosage form in accordance with claim 1 in which said longer axis has a length of 1.5 cm to 2.5 cm when said matrix is unswollen.

10. A controlled-release oral drug dosage form in accordance with claim 1 in which said matrix is a water-swellable polymer.

11. A controlled-release oral drug dosage form in accordance with claim 10 in which said water-swellable polymer is a member selected from the group consisting of poly(ethylene oxide), poly(vinyl alcohol), cellulose, alkyl-substituted cellulose, hydroxyalkyl-substituted cellulose, crosslinked polyacrylic acids, and xanthan gum.

12. A controlled-release oral drug dosage form in accordance with claim 10 in which said water-swellable polymer is a member selected from the group consisting of poly(ethylene oxide), poly(vinyl alcohol), hydroxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropylmethyl cellulose, and carboxymethyl cellulose.

13. A controlled-release oral drug dosage form in accordance with claim 10 in which said water-swellable polymer is a member selected from the group consisting of poly(ethylene oxide), hydroxypropylmethyl cellulose, and hydroxyethyl cellulose.

14. A controlled-release oral drug dosage form in accordance with claim 10 in which said water-swellable polymer is poly(ethylene oxide).

15. A controlled release oral drug dosage form in accordance with claim 1 in which said drug has a solubility in water at 37°

C. that is at least one part by weight of said drug in twenty parts by weight of water, and said matrix is a poly(ethylene oxide) having a viscosity-average molecular weight within the range of about 2,000,000 to about 7,000,000.

16. A controlled release oral drug dosage form in accordance with claim 1 in which said drug has a solubility in water at 37°

C. that is at least one part by weight of said drug in tenaparts by weight of water, and said matrix is a poly(ethylene oxide) having a viscosity-average molecular weight within the range of about 2,000,000 to about 7,000,000.

17. A controlled release oral drug dosage form in accordance with claim 1 in which said drug has a solubility in water at 37°

C. that is at least one part by weight of said drug in three parts by weight of water, and said matrix is a poly(ethylene oxide) having a viscosity-average molecular weight within the range of about 2,000,000 to about 7,000,000.

18. A controlled release oral drug dosage form in accordance with claim 1 in which-said drug has a solubility in water at 37°

C. that is from about 0.005% to about 10% by weight, and said matrix is a poly(ethylene oxide) having a vis sity-average molecular weight within the range of about 200,000 to about 2,000,000.

19. A controlled-release oral drug dosage form in accordance with claim 1 in which said drug has a solubility in water at 37°

C. that is from about 0.01% to about 5% by weight, and said matrix is a poly(ethylene oxide) having a viscosity-average molecular weight within the range of about 200,000 to about 2,000,000.

20. A controlled-release oral drug dosage form in accordance with claim 1 in which said drug is a member selected from the group consisting of lisinopril, acyclovir, rhetformin hydrochloride, baclofen, ciprofloxacin, furosemide, cyclosporin, sertraline hydrochloride, and calcium carbonate.

21. A controlled-release oral drug dosage form in accordance with claim 1 in which said drug is an antibiotic.

22. A controlled-release oral drug dosage form in accordance with claim 1 in which said drug is an angiotensin converting inhibitor.

23. A controlled-release oral drug dosage form in accordance with claim 22 in which said angiotensin converting inhibitor is a member selected from the group consisting of lisinopril, enalapril, captopril, and benazepril.

24. A controlled-release oral drug dosage form in accordance with claim 1 in which said drug is acyclovir.

25. A controlled-release oral drug dosage form in accordance with claim 1 in which said drug is metformin hydrochloride.

26. A controlled-release oral drug dosage form in accordance with claim 1 in which said drug is baclofen.

27. A controlled-release oral drug dosage form in accordance with claim 1 in which said drug is ciprofloxacin.

8. A controlled-release oral drug dosage form in accordance with claim in which said longer axis has a maximum length of 2.5 cm when said matrix is unswollen.