Apparatus and methods for use in administering medicaments by direct medicament contact to mucosal tissues

• US 5,122,127 A
• Filed: 09/05/1989
• Issued: 06/16/1992
• Est. Priority Date: 05/01/1985
• Status: Expired due to Fees

• Current Assignee: University of Utah (State of Utah), University of Utah Research Foundation (State of Utah), Anesta Corporation (Teva Pharmaceutical Industries Limited)
• Original Assignee: University of Utah (State of Utah)
• Inventors: Stanley, Theodore H.
• Primary Examiner(s): NOT, DEFINED
• Assistant Examiner(s): Polutta, Mark O.
• Application Number:
  US07/403,743
• Time in Patent Office: 1,015 Days
• Field of Search: 128/155, 128/156, 604/290, 604/303, 604/305, 604/306, 604/308, 604/303-309, 604/289, 604/890.1, 604/892.1, 424/434, 424/435, 424/443, 424/447-449
• US Class Current: 604/890.1
• CPC Class Codes: A23G 3/368 containing vitamins, antibiotics
• CPC Class Codes: A61K 31/465 Nicotine; Derivatives thereof
• CPC Class Codes: A61K 9/0056 Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
• CPC Class Codes: A61K 9/703 characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches
• 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

Abstract

Apparatus and methods for the dose-to-effect transmucosal administration of medicaments are disclosed. The present invention relates to such apparatus and methods which are useful in administering medicaments in a dose-to-effect manner such that sufficient drug is administered to produce precisely a desired effect. The invention also relates to an apparatus capable of placement directly on the patient'"'"'s buccal mucosa having the capability of adjusting the drug surface area in direct contact with the mucosal tissue thereby enabling the proper amount of therapeutic agent or drug to be administered while accounting for individual needs and susceptibilities of the drug.

Through the use of selected permeation enhancers, the present invention enables lipophilic and nonlipophilic medicaments, which are not suitable for oral administration, to be rapidly administered noninvasively. Employing the present invention the drug may be introduced into the patient'"'"'s bloodstream almost as fast as through injection, and much faster than using the oral administration route, while avoiding the negative aspects of both of these methods.

Claims

1. An apparatus for use in transmucosal delivery of a drug to a patient through the mucosal tissues of the mouth comprising:

a housing resistant to deformation defining a medicament chamber therein, said chamber having a base which defines at least one opening to said medicament chamber;

a quantity of medicament medium located within the medicament chamber, said medicament medium comprising a pharmaceutically effective dose of medicament;

means for temporarily positioning the housing against a mucosal membrane within the mouth, such that the opening to said medicament chamber is positioned over the mucosal membrane and such that the medicament medium within the medicament chamber is capable of contact with the mucosal membrane; and

means for adjusting the size of the opening to the medicament chamber in order to adjust the exposure of medicament medium within the medicament chamber to the mucosal membrane, the means for adjusting the size of the opening to the medicament chamber comprises;

a control member having a size and a shape similar to the medicament chamber base and having at least one opening corresponding to the opening of the medicament chamber base, said control member being positioned adjacent the medicament chamber base such that the respective openings of the control member and medicament chamber base are capable of movement with respect to each other; and

means for moving the control member relative to the medicament chamber base such that the size of the at least one opening to the medicament chamber may be modified by sliding the control member relative to the housing base in order to adjust the exposure of medicament medium within the medicament chamber to the mucosal membrane.

2. An apparatus for use in transmucosal delivery of a drug to a patient through the mucosal tissues of the mouth comprising:

a housing resistant to deformation defining a medicament chamber therein, said chamber having a base which defines at least one opening to aid medicament chamber;

a quantity of medicament medium located within the medicament chamber, said medicament medium comprising a pharmaceutically effective dose of medicament;

means for temporarily positioning the housing against a mucosal membrane within the mouth, such that the opening to said medicament chamber is positioned over the mucosal membrane and such that the medicament medium within the medicament chamber is positioned adjacent the mucosal membrane;

a substantially flat control member having a size and a shape similar to the medicament chamber base and having at least one opening corresponding to the opening of the medicament chamber base, said control member being positioned adjacent the medicament chamber base such that the respective openings of the control member and medicament chamber base are capable of movement with respect to each other; and

means for moving the control ember relative to the medicament chamber base such that the size of the at least one opening to the medicament chamber may be modified by sliding the control member relative to the housing base in order to adjust the exposure of medicament medium within the medicament chamber to the mucosal membrane in the range from zero area to the maximum area provided by the opening to the medicament chamber.

3. An apparatus for use in transmucosal delivery of a drug to a patient as defined in claim 2, further comprising holder means secured to the housing, said holder means being configured so as to permit convenient insertion and removal of the apparatus into and out of the mouth of the patient.

4. An apparatus for use in transmucosal delivery of a drug to a patient as defined in claim 3, wherein the holder means extends outside of the mouth.

5. An apparatus for use in transmucosal delivery of a drug to a patient as defined in claim 3, wherein the holder means allows the mouth or teeth of the patient to hold it in position adjacent the mucosal membrane.

6. An apparatus for use in transmucosal delivery of a drug to a patient as defined in claim 3, further comprising means for accessing the medicament chamber such that medicament medium may be introduced into the medicament chamber or removed therefrom.

7. An apparatus for use in transmucosal delivery of a drug to a patient as defined in claim 6, wherein means for accessing the medicament chamber permits medicament medium to be introduced into the medicament chamber or removed therefrom while the housing is positioned against the mucosal membrane.

8. An apparatus for use in transmucosal delivery of a drug to a patient as defined in claim 6, wherein the medicament chamber is reusable by adding new medicament medium to the medicament chamber after each use.

9. An apparatus for use in transmucosal delivery of a drug to a patient as defined in claim 3, wherein the medicament medium further comprises a permeation enhancer capable of increasing the medicament permeability across the mucosal membrane.

10. An apparatus for use in transmucosal delivery of a drug to a patient as defined in claim 9, wherein the permeation enhancer comprises a bile salt.

11. An apparatus for use in transmucosal delivery of a drug to a patient as defined in claim 9, wherein the permeation enhancer comprises a synthetic permeation enhancer.

12. An apparatus for use in transmucosal delivery of a drug to a patient as defined in claim 9, wherein the permeation enhancer comprises a fatty acid.

13. An apparatus for use in transmucosal delivery of a drug to a patient as defined in claim 9, wherein the permeation enhancer comprises a surfactant.

14. An apparatus for use in transmucosal delivery of a drug to a patient as defined in claim 9, wherein the permeation enhancer comprises an organic alcohol.

15. An apparatus for use in transmucosal delivery of a drug to a patient as defined in claim 3, wherein the medicament medium comprises the medicament within a pharmaceutically acceptable carrier.

16. An apparatus for use in transmucosal delivery of a drug to a patient as defined in claim 15, wherein the pharmaceutically acceptable carrier includes water.

17. An apparatus for use in transmucosal delivery of a drug to a patient as defined in claim 3, wherein the medicament medium comprises a hydrogel.

18. An apparatus for use in transmucosal delivery of a drug to a patient as defined in claim 3, wherein the medicament medium comprises a semisolid composition.

19. An apparatus for use in transmucosal delivery of a drug to a patient as defined in claim 3, wherein the medicament medium comprises a sponge-like material saturated with a medicament solution.

20. An apparatus for use in transmucosal delivery of a drug to a patient as defined in claim 3, wherein the medicament is potent and fast-acting.

21. An apparatus for use in transmucosal delivery of a drug to a patient as defined in claim 3, wherein the medicament has effects on the central nervous system of the patient.

22. An apparatus for use in transmucosal delivery of a drug to a patient as defined in claim 3, wherein the medicament has effects on the cardiovascular system of the patient.

23. An apparatus for use in transmucosal delivery of a drug to a patient as defined in claim 3, wherein the medicament has effect on the renal vascular system of the patient.

24. An apparatus for use in transmucosal delivery of a drug to a patient as defined in claim 3, wherein the medicament has effects on the respiratory system of the patient.

25. An apparatus for use in transmucosal delivery of a drug to a patient as defined in claim 3, wherein the medicament is a polypeptide drug.

26. An apparatus for use in transmucosal delivery of a drug to a patient as defined in claim 3, wherein the medicament is a protein drug.

27. An apparatus for use in transmucosal delivery of a drug to a patient as defined in claim 3, wherein the medicament is an opioid agonist.

28. An apparatus for use in transmucosal delivery of a drug to a patient as defined in claim 3, wherein the medicament is an opioid antagonist.

29. An apparatus for use in transmucosal delivery of a drug to a patient as defined in claim 3, wherein the medicament has antiemetic effects.

30. An apparatus for use in transmucosal delivery of a drug to a patient as defined in claim 3, wherein the medicament has antimigraine effects.

31. An apparatus for use in transmucosal delivery of a drug to a patient as defined in claim 3, wherein the medicament has bronchodilator effects.

32. An apparatus for use in transmucosal delivery of a drug to a patient as defined in claim 3, wherein the medicament has oxytocic effects.

33. An apparatus for use in transmucosal delivery of a drug to a patient as defined in claim 3, wherein the medicament has antidiuretic effects.

34. An apparatus for use in transmucosal delivery of a drug to a patient as defined in claim 3, wherein the medicament is insulin.

35. An apparatus for use in transmucosal delivery of a drug to a patient as defined in claim 3, wherein the medicament is fentanyl.

36. An apparatus for use in transmucosal delivery of a drug to a patient as defined in claim 3, wherein the medicament is ergotamine.