Controlled, sustained release delivery system for smoking cessation

• US 5,536,503 A
• Filed: 04/03/1995
• Issued: 07/16/1996
• Est. Priority Date: 05/07/1991
• Status: Expired due to Fees

• Current Assignee: DynaGen, Inc. (Sun Pharmaceutical Industries Limited)
• Original Assignee: DynaGen, Inc. (Sun Pharmaceutical Industries Limited)
• Inventors: Muni, Indu A., Kitchell, Judith P., Boyer, Yvonne N.
• Primary Examiner(s): AZPURU, CARLOS A
• Application Number:
  US08/415,859
• Time in Patent Office: 470 Days
• Field of Search: 424/423, 424/425, 424/426, 424/449, 424/451, 424/489, 424/501, 424/502, 514/810, 514/811, 514/812, 514/813, 514/963, 514/965, 514/953, 514/955
• US Class Current: 424/449
• CPC Class Codes: A61K 31/439 the ring forming part of a bridged ring system, e.g. quinuclidine 8-azabicyclo [3.2.1] octanes A61K31/46
• CPC Class Codes: A61K 31/44 Non condensed pyridines; Hydrogenated derivatives thereof
• CPC Class Codes: A61K 31/4425 Pyridinium derivatives, e.g. pralidoxime, pyridostigmine
• CPC Class Codes: A61K 31/445 Non condensed piperidines, e.g. piperocaine
• CPC Class Codes: A61K 31/4545 containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
• CPC Class Codes: A61K 31/455 Nicotinic acids, e.g. niacin; Derivatives thereof, e.g. esters, amides
• CPC Class Codes: A61K 31/465 Nicotine; Derivatives thereof
• CPC Class Codes: A61K 9/009 Sachets, pouches characterised by the material or function of the envelope with gastric retention A61K9/0065; sachets which are not administered but function merely as a container are classified according to the content, e.g. sachets comprising powder for reconstitution of a drink A61K9/0095
• CPC Class Codes: A61K 9/1647 Polyesters, e.g. poly(lactide-co-glycolide)
• CPC Class Codes: A61K 9/7023 Transdermal patches and similar drug-containing composite devices, e.g. cataplasms galenical aspects of iontophoretic devices A61K9/0009; microneedle arrays A61K9/0021; buccal patches A61K9/006
• CPC Class Codes: A61K 9/7084 Transdermal patches having a drug layer or reservoir, and one or more separate drug-free skin-adhesive layers, e.g. between drug reservoir and skin, or surrounding the drug reservoir; Liquid-filled reservoir patches
• CPC Class Codes: G01N 33/52 Use of compounds or compositions for colorimetric, spectrophotometric or fluorometric investigation, e.g. use of reagent paper and including single- and multilayer analytical elements immunological elements G01N33/54386; involving labelled immunochemicals G01N33/58; for haemoglobin or occult blood G01N33/72

Abstract

A drug delivery system useful in aiding individuals in the cessation of smoking or chewing nicotine containing products is described. The delivery system includes a physical constraint modulation system (PCMS™) containing lobeline. The drug delivery system is capable of delivering lobeline to an individual in a controlled, sustained release manner and providing long-term therapeutic levels of lobeline to the individual. The delivery of lobeline in such a manner reduces or eliminates the individual'"'"'s smoking or chewing habit. The PCMS may be a biodegradable polymer containing the lobeline capable of subcutaneous or intramuscular injection or implantation into the individual or may be part of a transdermal patch containing lobeline. Also described are methods of using the drug delivery systems and kits containing the drug delivery systems.

Claims

1. A transdermal drug delivery device comprising:

(a) a diffusion matrix layer, said diffusion matrix layer having a macroporous structure for holding a mixture of lobeline and an enhancer, and having a inner surface and an outer surface, said inner surface adapted to be applied on or toward the skin of a subject, said outer surface for application away from the skin of a subject,

(b) a mixture of lobeline, a polymer and an enhancer, said mixture having a quantity of lobeline sufficient for delivery of an effective dose of lobeline to said subject to diminish said subject'"'"'s desire for nicotine, said enhancer controlling the solubility of said lobeline in said polymer to release said lobeline in said polymer over time to allow lobeline to be absorbed from said polymer by said skin; and

(c) a backing layer, said backing layer comprising a film of elastomer on said outer surface of said diffusion matrix layer to prevent said mixture from being transmitted from the device, said diffusion matrix layer releasing an effective amount of lobeline to diminish said subject'"'"'s desire for nicotine for a period of at least one day.

2. The device of claim 1 wherein said enhancer is a non-solvent absorption enhancer.

3. The device of claim 1 wherein said mixture further comprises a anti-pruritic agent.

4. The device of claim 1 wherein said lobeline is in a free base form.

5. The device of claim 1 wherein said diffusion matrix layer is a reticulated macroporous foam.

6. The device of claim 5 wherein said foam has 10-40 pores per linear centimeter and an unfilled density of 0.01 to 0.5 mg/cm³.

7. The device of claim 6 wherein said foam is selected from polyurethanes and polyethylenes.

8. The device of claim 1 further comprising a pressure sensitive adhesive layer.

9. The device of claim 8 further comprising a release liner, said release liner for covering said pressure sensitive adhesive layer until said device is placed on said subject, said release liner removable to expose said pressure sensitive adhesive layer.

10. The device of claim 1 wherein said diffusion matrix layer releases 5 to 30 mg. lobeline per day.

17. A method of treating a subject for nicotine withdrawal or smoking cessation comprising the step of administering to said subject a device as claimed in claim 1 or 11.

11. A transdermal drug delivery device comprising:

(a) a rate controlling membrane having a bottom for being placed on or toward the skin of a subject and a top for being placed away from the skin of a subject;

(b) a backing layer fixed to said top of said rate controlling membrane to form a first chamber and a second chamber, said first chamber for containing lobeline and said second chamber for containing a delivery substance, said first and second chamber capable of being placed in fluid communication;

(c) lobeline, held in a solid form in said first chamber, which upon dissolution in said first or second chamber enters said rate controlling membrane for transdermal delivery to the skin; and

(d) a drug delivery substance, held within said second chamber, said drug delivery substance for dissolving said lobeline in said first chamber and carrying said lobeline through said rate controlling membrane to deliver an amount of lobeline to a subject effective to diminish the subject'"'"'s desire for nicotine.

12. The device of claim 11 further comprising a pressure sensitive adhesive layer.

13. The desire of claim 12 further comprising a release layer, said release layer covering said pressure sensitive adhesive layer until use, said release layer removable from said pressure sensitive layer to allow said pressure sensitive layer to be applied to a subject.

14. The device of claim 11 wherein said first and second chambers are placed in communication by breaking a pressure seal.

15. The device of claim 11 wherein said delivery substance is selected from alcoholic, aqueous, and aqueous/alcoholic solutions.

16. The device of claim 11 wherein said first chamber contains sufficient lobeline to deliver 5-30 mg. of lobeline per day to a subject.