Controlled release of drugs

• US 6,669,954 B2
• Filed: 01/24/2001
• Issued: 12/30/2003
• Est. Priority Date: 01/25/2000
• Status: Expired due to Fees

• Current Assignee: TSRL, Inc.
• Original Assignee: Gordon L. Amidon, John R. Crison
• Inventors: Amidon, Gordon L., Crison, John R.
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): Bennett, Rachel M.
• Application Number:
  US09/768,852
• Publication Number:
  US 20020004067A1
• Time in Patent Office: 1,070 Days
• Field of Search: 424/472, 424/453, 424/464, 424/466, 424/468, 424/470, 424/456
• US Class Current: 424/456
• 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

A device for controlled release of pharmaceutical agents and a method for use of the device. The drug delivery device comprises a covered container with an aperture and an aperture cover, containing a pharmaceutical agent and an excipient formulation.

Claims

1. A drug delivery system comprising:

(a) a therapeutic amount of a pharmaceutical agent;

(b) a container having (i) at least one aperture and (ii) a wall having an inside and an outside;

(c) an excipient formulation disposed in said container regulating a diffusional boundary for said pharmaceutical agent, wherein the diffusional boundary layer is confined within said container for a period of time to allow drug delivery to a desired location and continuously releasing said pharmaceutical agent upon solvation at a rate of less than one-fifth of the initial release of said pharmaceutical agent in an uncoated form, the excipient formulation comprising a release control agent and an ingredient selected from the group consisting of;

a lubricating agent, a filling agent and a mixture thereof, the ratio of the release control agent to the ingredient ranging from 0.2 to 170; and

(d) a cover layer adhered to the wall, wherein at least one of the container or the cover layer is semi-permeable to said pharmaceutical agent.

2. The drug delivery system of claim 1 further comprising an aperture cover that is removable to expose the at least one aperture after a preselected length of time.

3. The drug delivery system of claim 1 wherein said container comprises a biocompatible polymer.

4. The drug delivery system of claim 1 wherein said container is selected from the group consisting of:

hard gelatin, soft gelatin, hydroxypropylmethylcellulose and starch.

5. The drug delivery system of claim 1 wherein the pharmaceutical agent is selected from the group consisting of:

organic, inorganic and organometallic.

6. The drug delivery system of claim 1 wherein the pharmaceutical agent has a molecular weight in the range of about 50 to about 10,000,000.

7. The drug delivery system of claim 1 wherein the pharmaceutical agent is selected from the group consisting of:

an analgesic, an anesthetic, an anthelminthic, an antiallergic, an antiarrhythmic, an anti-asthmatic, an antibiotic, an anticonvulsant, an antidepressant, an antidiabetic, an antifungal, an antihypertensive, an anti-inflammatory agent, anti-migraine, an antineoplastic, an antiparasitic, an antitumor agent, an anti-ulcer agent, an antiviral, an anxiolytic, a bronchodilator, a cough or cold agent, a cytostatic, a hypnotic, a hypoglycemic, a metastasis inhibitor, a muscle relaxant, a neoplastic, a sedative and a tranquilizer compound.

8. The drug delivery system of claim 1 wherein the pharmaceutical agent is pseudoephedrine.

9. The drug delivery system of claim 1 wherein the pharmaceutical agent is nifedipine.

10. The drug delivery system of claim 1 wherein the pharmaceutical agent is acetominophen.

11. The drug delivery system of claim 1 wherein the pharmaceutical agent is glipizide.

12. The drug delivery system of claim 1 wherein said formulation remains disposed in said container when hydrated for a time effective to regulate release of said pharmaceutical agent.

13. The drug delivery system of claim 1 wherein said formulation comprises at least one ingredient selected from the group consisting of:

a release control component, a lubricating agent and a filling agent.

14. The drug delivery system of claim 13 comprising at least one ingredient selected from the group consisting of:

hydroxyalkylcellulose, carbomer, magnesium stearate and a saccharide.

15. The drug delivery system of claim 14 wherein the hydroxyalkylcellulose is present in amounts from about 0 to about 85% weight/weight, the carbomer is present in amounts from about 0 to about 30% weight/weight, the magnesium stearate is present in amounts from about 0.5 to about 3% weight/weight and the saccharide is present in amounts from about 0 to about 70% weight/weight.

16. The drug delivery system of claim 1 wherein said cover layer allows the inward passage of water.

17. The drug delivery system of claim 1 wherein said cover layer comprises a cellulose acetate material selected from the group consisting of:

cellulose acetate butyrate, cellulose derivates and polyurethane.

18. The drug delivery system of claim 1 wherein said cover layer adheres to the outside of the wall.

19. The drug delivery system of claim 1 wherein said cover layer adheres to the inside of the wall.

20. The drug delivery system of claim 1 wherein said cover layer adheres to the inside and the outside of the wall.

21. A process for drug delivery comprising the step of administering to an individual a drug delivery device comprising:

(a) a therapeutic amount of a pharmaceutical agent;

(b) a container having (i) at least one aperture and (ii) a wall having an inside and an outside;

(c) an excipient formulation disposed in said container regulating a diffusional boundary for said pharmaceutical agent, wherein the diffusional boundary layer is confined within said container for a period of time to allow drug delivery to a desired location and continuously releasing said pharmaceutical agent upon solvation at a rate of less than one-fifth of the initial release of said pharmaceutical agent in an uncoated form, the excipient formulation comprising a release control agent and an ingredient selected from the group consisting of;

a lubricating agent, a filling agent and a mixture thereof, the ratio of the release control agent to the ingredient ranging from 0.2 to 170; and

(d) a cover layer adhered to the wall, wherein at least one of the container or the cover layer is semi-permeable to said pharmaceutical agent.

22. The process for drug delivery of claim 21 further comprising an aperture cover that is removable to expose the at least one aperture after a preselected length of time.

23. The process for drug delivery of claim 21 wherein said container comprises a biocompatible polymer.

24. The process for drug delivery of claim 21 wherein said container is selected from the group consisting of:

hard gelatin, soft gelatin, hydroxypropylmethylcellulose and starch.

25. The process for drug delivery of claim 21 wherein the pharmaceutical agent is selected from the group consisting of:

organic, inorganic and organometallic.

26. The process for drug delivery of claim 21 wherein the pharmaceutical agent has a molecular weight in the range of about 50 to about 1,000,000.

27. The process for drug delivery of claim 21 wherein the pharmaceutical agent is selected from the group consisting of:

antihypertensives, antiallergics, anxiolytics, bronchodilators, anti-asthmatics, hypoglycemics, cough or cold agents, neoplastics, anti-ulcer agents, antineoplastics, antitumor agents, hypnotics, sedatives, tranquilizers, anesthetics, muscle relaxants, anticonvulsants, antidepressants, antibiotics, analgesics, antivirals, anti-inflammatory agents, antidiabetics, anti-migraines, cytostatics and metastasis inhibitors, antiarrhythmics, antibiotics, antifungals, antivirals, anthelminthics, and antiparasitic compounds.

28. The process for drug delivery of claim 21 wherein the pharmaceutical agent is pseudoephedrine.

29. The process for drug delivery of claim 21 wherein the pharmaceutical agent is nifedipine.

30. The process for drug delivery of claim 21 wherein the pharmaceutical agent is acetominophen.

31. The drug delivery system of claim 21 wherein the pharmaceutical agent is glipizide.

32. The process for drug delivery of claim 21 wherein said formulation remains disposed in said container when hydrated for a time effective to regulate release of said pharmaceutical agent.

33. The process for drug delivery of claim 21 wherein the formulation comprises at least one ingredient selected from the group consisting of:

a release control component, a lubricating agent and a filling agent.

34. The process for drug delivery of claim 21 comprising at least one ingredient selected from the group consisting of:

hydroxyalkylcellulose, carbomer, magnesium stearate and a saccharide.

35. The process for drug delivery of claim 32 wherein the hydroxyalkylcellulose is hydroxypropylmethylcellulose that is present in amounts from about 0 to about 85% weight/weight, the carbomer is present in amounts from about 0 to about 30% weight/weight, the magnesium stearate is present in amounts from about 0.5 to about 3% weight/weight and the saccharide is present in amounts from about 0 to about 70% weight/weight.

36. The process for drug delivery of claim 21 wherein said cover layer allows the inward passage of water.

37. The process for drug delivery of claim 21 wherein said cover layer adheres to the outside of the wall.

38. The process for drug delivery of claim 21 wherein said cover layer adheres to the inside of the wall.

39. The process for drug delivery of claim 21 wherein said cover layer adheres to the inside and the outside of the wall.

40. The process for drug delivery of claim 21 wherein said cover layer comprises a material selected from the group consisting of:

cellulose acetate butyrate, cellulose derivatives and polyurethane.

41. The process for drug delivery of claim 21 wherein the individual is selected from the group consisting of:

sheep, cattle, horses, goats, pigs, chickens, dogs and cats.

42. The process for drug delivery of claim 21 wherein the individual is human.

43. The process for drug delivery of claim 21 wherein the administration is by a route selected from the group consisting of:

oral, rectal, parenteral, intravenous, intramuscular, subcutaneous, intracisternal, intravaginal, intraperitonal, intravesical, intraventricular, intracranial, and intrathecal.