Nicotine-containing pharmaceutical composition

Abstract

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.