INTRAORAL DELIVERY OF NICOTINE FOR SMOKING CESSATION
Dosage forms of a nicotine delivery system are disclosed in which a mucoadhesive film, made up of one or more non-microbial hydrocolloid(s) and an effective dose of nicotine, dissolves when applied intraorally to release the nicotine which is absorbed through the oramucosac and directly reaches systemic circulation. Methods for preparing various versions of the dosage forms are disclosed. Methods to assist smoking cessation or provide substitutes for smoking by administrating the dosage form are also provided.
1 . A mucoadhesive film consisting essentially of
an effective dose of nicotine and
at least one non-microbial hydrocolloid,
wherein
a) the nicotine is present in a single layer;
b) wherein the non-microbial hydrocolloid has a hydration rate at 25° C. and 75% relative humidity of 5 to 20% per 24 hours;
c) the mucoadhesive film provides a nicotine peak plasma level within 15 minutes of administration to a subject; and
d) the mucoadhesive film disintegrates within 1 to 600 seconds upon application in the oral cavity or dissolves within 0.5 to 60 minutes and wherein, the non-microbial hydrocolloid is a hydroxypropyl methylcellulose having a methoxy content in the range of 19 to 30%, hydroxypropyl content in the range of 7 to 12% and molecular weight of approximately 50,000 to 250,000 daltons.
2 . The mucoadhesive film of claim 1 , wherein the mucoadhesive film is a monolayer intraoral film.
3 . The mucoadhesive film of claim 1 , wherein the mucoadhesive film is a bilayer intraoral film.
4 . The mucoadhesive film of claim 2 , wherein the nicotine in the mucoadhesive film is in neutral form.
5 . The mucoadhesive film of claim 3 , wherein the nicotine in the mucoadhesive film is in ionized form.
6 . The mucoadhesive film of claim 4 , wherein at least 50% of the nicotine in the mucoadhesive film is in neutral form.
7 . The mucoadhesive film of claim 5 , wherein at least 90% of the nicotine in the mucoadhesive film is in ionized form.
8 . The mucoadhesive film of claim 1 , wherein the mucoadhesive film has a water content in the range of 0.5 to 10%.
9 . The mucoadhesive film of claim 3 , wherein the film has a disintegration time in the range of 1 to 300 seconds.
10 . The mucoadhesive film of claim 1 , wherein the film has a dissolving time in the range of 0.5 to 5 minutes.
11 . The mucoadhesive film of claim 1 , wherein the dosage form further comprises at least one of an emulsifier, a release modifier, a taste modifying agent, a plasticizer, a water soluble inert filler, a preservative, a buffering agent, a stabilizer and a coloring agent.
12 . A method of administering nicotine to a subject comprising, administering to a subject a mucoadhesive film according to claim 1 , wherein the subject experiences a peak nicotine plasma level within 15 minutes of administration of the mucoadhesive film.
13 . A bilayer mucoadhesive film consisting essentially of
a first layer having an effective dose of nicotine and at least one non-microbial hydrocolloid; and
a nicotine-free second layer having an alkalizing agent and at least one non-microbial hydrocolloid
wherein
a) the non-microbial hydrocolloid in each layer has a hydration rate at 25° C. and 75% relative humidity of 5 to 20% per 24 hours;
b) the mucoadhesive film provides a nicotine peak plasma level within 15 minutes of administration to a subject; and
c) the mucoadhesive film disintegrates within 1 to 600 seconds upon application in the oral cavity or dissolves within 0.5 to 60 minutes, and wherein the non-microbial hydrocolloid is a hydroxypropyl methylcellulose having a methoxy content in the range of 19 to 30%, hydroxypropyl content in the range of 7 to 12% and molecular weight of approximately 50,000 to 250,000 daltons.
14 . The mucoadhesive film of claim 13 , wherein the mucoadhesive film releases at least 92.01±4.53% of the original nicotine dose within 60 seconds of administration to the subject.
15 . The mucoadhesive film of claim 13 , wherein at least 90% of the nicotine in the mucoadhesive film is in ionized form.
16 . The mucoadhesive film of claim 13 , wherein the alkalizing agent is sodium bicarbonate.
17 . A bilayer mucoadhesive film consisting essentially of
a) a first layer containing an effective dose of nicotine and a non-microbial hydrocolloid; and
b) a nicotine free second layer containing an alkalizing agent and a non-microbial hydrocolloid;
wherein the non-microbial hydrocolloid in each layer has a hydration rate at 25° C. and 75% relative humidity of 5 to 20% per 24 hours; and the mucoadhesive film releases at least 92.01±4.53% of the original nicotine dose within 60 seconds of administration to the subject.