NICOTINE DOSAGE REGIMEN
The invention relates to dosage regimens for an inhalable formulation comprising nicotine, and to devices for delivering said dosage regimens.
1 .- 16 . (canceled)
17 . A method of preventing nicotine craving associated with tobacco dependence in a patient, said method comprising the steps of:
providing an inhalable formulation comprising a deliverable daily dose of less than 60 mg of nicotine or a pharmaceutically acceptable salt thereof in at least one pressurized container;
filling a simulated cigarette with a charge of the orally inhalable formulation from the at least one pressurized container, the charge containing 0.1 mg to 1 mg of nicotine or a pharmaceutically acceptable salt thereof, the simulated cigarette including: an outlet, a reservoir for holding the charge of the orally inhalable formulation, and an outlet; and
delivering, from the outlet of the simulated cigarette, at least a portion of the orally inhalable formulation in the form of droplets to the patient's lungs, wherein:
at least 90% (vol) of the delivered droplets have a diameter of 10 micrometers or less and at least 10% (vol) of the delivered droplets have a diameter between 0.4 and 0.5 micrometers so that at least 90% of the nicotine or the pharmaceutically acceptable salt thereof in the delivered portion of the orally inhalable formulation enters the patient's bloodstream via the patient's lungs.
18 . The method according to claim 17 , further comprising:
when the full charge of the orally inhalable formulation has been delivered to the patient's lungs, refilling the simulated cigarette with a subsequent charge of the orally inhalable formulation from the at least one pressurized container.
19 . The method according to claim 18 , wherein the subsequent charge contains more nicotine or the pharmaceutically acceptable salt thereof compared to the first charge.
20 . The method according to claim 17 , wherein the orally inhalable formulation further comprises a propellant.
21 . The method according to claim 20 , wherein the propellant is HFA.
22 . The method according to claim 17 , wherein:
the orally inhalable formulation further comprises a monohydric alcohol; and a glycol and/or glycol ether, and
the ratio of monohydric alcohol:glycol or glycol ether by weight is from 6:1 to 1:1.
23 . The method according to claim 22 , wherein the monohydric alcohol is ethanol.
24 . The method according to claim 22 , wherein the glycol and/or glycol ether is propylene glycol.
25 . The method according to claim 17 , wherein the orally inhalable formulation further comprises, based on the total weight of the formulation: from 0.03-0.05% w/w menthol, from 0.25-0.4% w/w propylene glycol, from 0.9-1% w/w ethanol, saccharin, and from 0.025% w/w to 0.03% w/w nicotine or the pharmaceutically acceptable salt thereof, the balance being HFA-134a, wherein the ratio of nicotine or the pharmaceutically acceptable salt thereof to saccharin is from 9.5:1 to 8:1% w/w.
26 . The method according to claim 17 , wherein the orally inhalable formulation further comprises, based on the total weight of the formulation: from 0.03-0.05% w/w menthol, from 0.25-0.4% w/w propylene glycol, from 0.9-1% w/w ethanol, saccharin, and from 0.054% w/w to 0.058% w/w nicotine or the pharmaceutically acceptable salt thereof, the balance being HFA-134a, wherein the ratio of nicotine or the pharmaceutically acceptable salt thereof to saccharin is from 9.5:1 to 8:1% w/w.
27 . The method according to claim 17 , wherein the orally inhalable formulation further comprises, based on the total weight of the formulation: from 0.03-0.05% w/w menthol, from 0.25-0.4% w/w propylene glycol, from 0.9-1% w/w ethanol, saccharin, and from 0.08% w/w to 0.088% w/w nicotine or the pharmaceutically acceptable salt thereof, the balance being HFA-134a, wherein the ratio of nicotine or the pharmaceutically acceptable salt thereof to saccharin is from 9.5:1 to 8:1% w/w.
28 . The method according to claim 17 , wherein the orally inhalable formulation is delivered from the outlet of the simulated cigarette when the patient activates a breath-actuated valve included in the simulated cigarette.
29 . The method according to claim 17 , wherein the simulated cigarette further comprises a capillary plug extending from the vicinity of the outlet valve into the reservoir, filling at least 50% of the volume of the reservoir and being configured to wick the orally inhalable composition towards the outlet.
30 . A method of preventing nicotine craving associated with tobacco dependence in a patient, said method comprising the steps of:
providing, in at least one pressurized container, an inhalable formulation comprising: a deliverable daily dose of less than 60 mg of nicotine or a pharmaceutically acceptable salt thereof, a monohydric alcohol, and a glycol and/or glycol ether, the ratio of monohydric alcohol:glycol or glycol ether by weight being from 6:1 to 1:1;
filling a simulated cigarette with a charge of the orally inhalable formulation from the at least one pressurized container, the charge containing 0.1 mg to 1 mg of nicotine or a pharmaceutically acceptable salt thereof, the simulated cigarette including: an outlet, a reservoir for holding the charge of the orally inhalable formulation, and an outlet; and
delivering, from the outlet of the simulated cigarette, at least a portion of the orally inhalable formulation in the form of droplets to the patient's lungs, wherein at least 90% of the nicotine or the pharmaceutically acceptable salt thereof in the delivered portion of the orally inhalable formulation enters the patient's bloodstream via the patient's lungs.
31 . The method according to claim 30 , wherein at least 90% (vol) of the delivered droplets have a diameter of 10 micrometers or less and at least 10% (vol) of the delivered droplets have a diameter between 0.4 and 0.5 micrometers.
32 . The method according to claim 33 , wherein:
the orally inhalable formulation further comprises a monohydric alcohol; and a glycol and/or glycol ether, and
the ratio of monohydric alcohol:glycol or glycol ether by weight is from 6:1 to 1:1.
33 . The method according to claim 32 , wherein the monohydric alcohol is ethanol.
34 . The method according to claim 30 , further comprising:
when the full charge of the orally inhalable formulation has been delivered to the patient's lungs, refilling the simulated cigarette with a subsequent charge of the orally inhalable formulation from the at least one pressurized container.
35 . The method according to claim 34 , wherein the subsequent charge contains more nicotine or the pharmaceutically acceptable salt thereof compared to the first charge.
36 . The method according to claim 30 , wherein the orally inhalable formulation is delivered from the outlet of the simulated cigarette when the patient activates a breath-actuated valve included in the simulated cigarette.