Oral drug delivery system

• US 8,133,507 B2
• Filed: 12/15/2003
• Issued: 03/13/2012
• Est. Priority Date: 12/13/2002
• Status: Expired due to Fees

• Current Assignee: DURECT Corporation
• Original Assignee: DURECT Corporation
• Inventors: Yum, Su Il, Schoenhard, Grant, Tipton, Arthur J., Gibson, John W., Middleton, John C.
• Primary Examiner(s): FUBARA, BLESSING M
• Application Number:
  US10/737,144
• Publication Number:
  US 20040161382A1
• Time in Patent Office: 3,011 Days
• Field of Search: 424/1.25, 424/451, 424/400, 424/456, 514/960, 514/159, 514/282, 514/778
• US Class Current: 424/456
• CPC Class Codes: A61K 31/4458 only substituted in position 2, e.g. methylphenidate
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: A61K 47/14 Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
• CPC Class Codes: A61K 47/26 Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
• CPC Class Codes: A61K 47/38 Cellulose; Derivatives thereof
• CPC Class Codes: A61K 9/0053 Mouth and digestive tract, i.e. intraoral and peroral administration rectal administration A61K9/0031
• 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: A61K 9/4825 Proteins, e.g. gelatin gelatin capsule shells with substantial amounts of other macromolecular substances A61K9/4816
• CPC Class Codes: A61K 9/4858 Organic compounds
• CPC Class Codes: A61K 9/4866 Organic macromolecular compounds
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/20 Hypnotics; Sedatives
• CPC Class Codes: A61P 25/26 Psychostimulants, e.g. nicotine, cocaine
• CPC Class Codes: A61P 25/36 Opioid-abuse
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

Dosage forms and drug delivery devices suitable for administration of pharmaceutical compounds and compositions, including the oral drug administration of compounds.

Claims

1. An oral formulation comprising:

a drug selected from the group consisting of buprenorphine, butorphanol, hydrocodone, hydromorphone, levorphanol, meperidine, methadone, morphine, oxycodone, oxymorphone, and tramadol, or pharmacologically effective salts thereof;

sucrose acetate isobutyrate (SAIB);

a cellulose acetate butyrate (CAB) having a number average molecular weight ranging from 66,000 Daltons to 83,000 Daltons;

isopropyl myristate (IPM); and

a solvent in which the CAB is soluble.

2. The oral formulation of claim 1, wherein the solvent is triacetin or ethyl lactate.

3. The oral formulation of claim 1, wherein the solvent is triacetin.

4. The oral formulation of claim 1, wherein the solvent comprises propylene carbonate, N-methylpyrrolidone (NMP), glycofurol, alpha-tocopherol, diethyl phthalate, or polyethylene glycol 400 (PEG 400).

5. The oral formulation of claim 1, wherein the CAB has a butyryl content ranging from about 17% to about 38%.

6. The oral formulation of claim 1, wherein the CAB has an acetyl content ranging from about 13% to about 30%.

7. The oral formulation of claim 1, wherein the CAB has a hydroxyl content ranging from about 0.8% to about 1.7%.

8. The oral formulation of claim 1, wherein the CAB has a butyryl content ranging from about 17% to about 38%, an acetyl content ranging from about 13% to about 30%, and a hydroxyl content ranging from about 0.8% to about 1.7%.

9. The oral formulation of claim 1, wherein the formulation comprises from about 1 to about 8.6 weight percent of the CAB.

10. The oral formulation of claim 9, wherein the drug is hydrocodone, hydromorphone, levorphanol, morphine, oxymorphone or oxycodone.

11. The oral formulation of claim 9, wherein the drug is oxycodone.

12. The oral formulation of claim 1, wherein the formulation comprises from about 20 to about 50 weight percent of the solvent.

13. The oral formulation of claim 1, wherein the formulation comprises from about 1 to about 75 weight percent IPM.

14. An oral dosage form comprising the formulation of claim 1, wherein the formulation is contained in a capsule.

15. The oral dosage form of claim 14, wherein the capsule comprises gelatin or hydroxyl propylmethyl cellulose.

16. The oral dosage form of claim 14, wherein the capsule is a hard capsule comprising gelatin or hydroxyl propylmethyl cellulose.

17. A method of treating a subject, the method comprising:

orally administering to the subject an effective amount of the oral dosage form of claim 14.

18. The oral formulation of claim 1, wherein the formulation comprises:

from about 1 to about 8.6 weight percent of the CAB;

from about 20 to about 50 weight percent of the solvent; and

from about 1 to about 75 weight percent IPM.

19. The oral formulation of claim 18, wherein the formulation comprises from 3 to 7.8 weight percent of the CAB.

20. The oral formulation of claim 19, wherein the CAB has a butyryl content ranging from about 17% to about 38%.

21. The oral formulation of claim 19, wherein the CAB has an acetyl content ranging from about 13% to about 30%.

22. The oral formulation of claim 19, wherein the CAB has a hydroxyl content ranging from about 0.8% to about 1.7%.

23. The oral formulation of claim 19, wherein the CAB has a butyryl content ranging from about 17% to about 38%, an acetyl content ranging from about 13% to about 30%, and a hydroxyl content ranging from about 0.8% to about 1.7%.

24. The oral formulation of claim 23, wherein the solvent is triacetin.

25. The oral formulation of claim 24, wherein the drug is oxycodone.

26. An oral dosage form comprising the formulation of claim 18, wherein the formulation is contained in a capsule.

27. The oral dosage form of claim 26, wherein the capsule comprises gelatin or hydroxyl propylmethyl cellulose.

28. The oral dosage form of claim 27, wherein the capsule is a hard capsule comprising gelatin or hydroxyl propylmethyl cellulose.

29. A method of treating a subject, the method comprising:

orally administering to the subject an effective amount of the oral formulation of claim 1.