NICOTINE-CONTAINING PHARMACEUTICAL COMPOSITION
A composition intended to be employed for therapeutic purposes incorporates a nicotinic compound, a sugar substitute, and a sugar alcohol syrup. Representative forms of nicotine include free base (e.g., as a mixture of nicotine and microcrystalline cellulose), a nicotine salt (e.g., as nicotine bitartrate) or nicotine polacrilex. The composition is useful for treatment of central nervous system conditions, diseases, and disorders, and as a nicotine replacement therapy.
1 . A nicotine-containing pharmaceutical composition, comprising:
a. a nicotinic compound;
b. a sugar substitute in an amount of at least about 80% by weight; and
c. a sugar alcohol syrup,
wherein the sugar substitute is a non-hygroscopic sugar alcohol capable of forming a glassy matrix and wherein the composition is in a pharmaceutically acceptable form adapted for oral delivery of the composition.
2 . The pharmaceutical composition of claim 1 , wherein at least a portion of the nicotinic compound is in the form of a free base, a salt, a complex, or a solvate.
3 . The pharmaceutical composition of claim 2 , wherein the nicotinic compound is nicotine polacrilex.
4 . The pharmaceutical composition of claim 1 , wherein the nicotinic compound is sorbed onto a porous particulate carrier.
5 . The pharmaceutical composition of claim 4 , wherein the porous particulate carrier comprises microcrystalline cellulose.
6 . The pharmaceutical composition of claim 1 , wherein the sugar substitute is isomalt.
7 . The pharmaceutical composition of claim 1 , wherein the sugar alcohol syrup is in an amount sufficient to slow recrystallization of the sugar substitute in melted form.
8 . The pharmaceutical composition of claim 1 , wherein the sugar alcohol syrup is maltitol syrup or xylitol syrup.
9 . The pharmaceutical composition of claim 1 , wherein the composition comprises at least about 85% by weight of the sugar substitute.
10 . The pharmaceutical composition of claim 1 , wherein the composition comprises at least about 4.0% by weight of sugar alcohol syrup.
11 . The pharmaceutical composition of claim 1 , wherein the composition comprises at least about 4.5% by weight of sugar alcohol syrup.
12 . The pharmaceutical composition of claim 1 , wherein the composition is in the form of a lozenge or tablet.
13 . The pharmaceutical composition of claim 1 , wherein the composition is translucent.
14 . The pharmaceutical composition of claim 1 , wherein the composition further comprises one or more flavorants.
15 . The pharmaceutical composition of claim 14 , wherein the amount of flavorant is from about 0.1 to about 0.5 percent by weight of the pharmaceutical composition.
16 . The pharmaceutical composition of claim 14 , wherein the flavorant is vanillin and/or mint flavor.
17 . The pharmaceutical composition of claim 1 , further comprising at least one sweetener.
18 . The pharmaceutical composition of claim 17 , wherein the at least one sweetener comprises sucralose.
19 . The pharmaceutical composition of claim 1 , further comprising NaCl.
20 . The pharmaceutical composition of claim 19 , wherein the amount of NaCl is from about 0.5 to about 1 percent by weight of the pharmaceutical composition.
21 . A method for treating a human subject having a condition, disease, or disorder responsive to stimulation of nicotinic acetylcholinergic receptors, comprising orally administering an effective amount of a pharmaceutical composition according to claim 1 to said human subject.
22 . The method of claim 21 , wherein said administering step comprises administering the pharmaceutical composition to a human subject having a condition, disease, or disorder of the central nervous system.
23 . The method of claim 21 , wherein said administering step comprises administering the pharmaceutical composition to a human subject as a smoking cessation aid.
24 . The method of claim 21 , wherein the nicotinic compound is nicotine free base or nicotine polacrilex.
25 . The method of claim 21 , wherein the nicotinic compound is sorbed onto a porous particulate carrier.
26 . The method of claim 25 , wherein the porous particulate carrier comprises microcrystalline cellulose.
27 . The method of claim 21 , wherein the composition is in the form of a lozenge or tablet.
28 . A method of preparing a nicotine-containing pharmaceutical composition according to claim 1 , comprising:
(i) mixing a non-hygroscopic sugar substitute capable of forming a glassy matrix in an amount of at least about 80% by weight and a sugar alcohol syrup in a melted state to form a mixture;
(ii) cooling the mixture and incorporating a nicotinic compound into the cooled mixture; and
(iii) further cooling the mixture to room temperature to form a solid nicotine-containing pharmaceutical composition.
29 . The method of claim 28 , wherein at least a portion of the nicotinic compound is in the form of a free base, a salt, a complex, or a solvate.
30 . The method of claim 28 , wherein the nicotinic compound is nicotine polacrilex.
31 . The method of claim 28 , wherein the nicotinic compound is sorbed onto a porous particulate carrier.
32 . The method of claim 31 , wherein the porous particulate carrier comprises microcrystalline cellulose.
33 . The method of claim 28 , wherein the sugar substitute is isomalt.
34 . The method of claim 28 , wherein the sugar alcohol syrup is in an amount sufficient to slow recrystallization of the sugar substitute in melted form.
35 . The method of claim 28 , wherein the sugar alcohol syrup is maltitol syrup or xylitol syrup.
36 . The method of claim 28 , wherein the pharmaceutical composition comprises at least about 85% by weight of the sugar substitute.
37 . The method of claim 28 , wherein the pharmaceutical composition comprises at least about 4.0% by weight of sugar alcohol syrup.
38 . The method of claim 28 , wherein the pharmaceutical composition comprises at least about 4.5% by weight of sugar alcohol syrup.
39 . The method of claim 28 , wherein the composition is in the form of a lozenge or tablet.
40 . The method of claim 28 , wherein the composition is translucent.
41 . The method of claim 28 , further comprising adding one or more components selected from the group consisting of flavorants, sweeteners, and NaCl.
42 . The method of claim 41 , wherein the amount of flavorant is from about 0.1 to about 0.5 percent by weight of the pharmaceutical composition.
43 . The method of claim 41 , wherein the flavorant is vanillin or mint flavor.
44 . The method of claim 41 , wherein the sweetener comprises sucralose.
45 . The method of claim 41 , wherein the amount of NaCl is from about 0.5 to about 1 percent by weight of the pharmaceutical composition.
46 . The method of claim 28 , wherein the mixing step comprises heating the sugar substitute and the sugar alcohol syrup to a temperature above the hard crack stage of the sugar substitute and wherein the incorporating step comprises adding a nicotinic compound to the mixture at a temperature below the hard crack stage of the sugar substitute.
47 . The method of claim 46 , wherein the hard crack stage is about 145° C. to about 155° C. and the sugar substitute and the sugar alcohol syrup are heated at a temperature between the hard crack stage and about 171° C.