Multi-layer nicotine-containing pharmaceutical composition

Abstract

The invention provides a multi-layered pharmaceutical composition comprising two or more formulations with varying properties. In some embodiments, the pharmaceutical compositions provide combinations of different organoleptic properties within the same product. In certain embodiment, these combinations allow for a modified release profile of active ingredients as the user enjoys the pharmaceutical composition. The invention further provides methods for making and using the pharmaceutical composition.

1 . A multi-layered pharmaceutical composition comprising two or more formulations having different organoleptic properties, wherein the formulations are selected from the group consisting of:
 i) a dissolvable formulation comprising a sugar substitute in an amount of at least about 80% by weight and a sugar alcohol syrup;   ii) a meltable formulation comprising a lipid having a melting point of about 36° C. to about 45° C.;   iii) a pastille formulation comprising a polysaccharide filler;   iv) a pastille formulation comprising a sugar alcohol and a natural gum binder component;   v) a chewable formulation comprising a binder, an emulsifier, and a lipid having a melting point of about 36° C. to about 45° C.; and   vi) a hard coating formulation comprising a binder, a sugar substitute, and a sugar alcohol syrup;   wherein at least one fat nulation further comprises one or more nicotinic compounds.   
     
     
         2 . The multi-layered pharmaceutical composition of  claim 1 , wherein all formulations of the multi-layered pharmaceutical composition comprise one or more nicotinic compounds. 
     
     
         3 . The multi-layered pharmaceutical composition of  claim 1 , wherein the one or more nicotinic compounds are independently in the form of a free base, a salt, a complex, or a solvate. 
     
     
         4 . The multi-layered pharmaceutical composition of  claim 3 , wherein the one or more nicotinic compounds comprise nicotine polacrilex. 
     
     
         5 . The multi-layered pharmaceutical composition of  claim 1 , wherein the one or more nicotinic compounds comprise a nicotinic compound sorbed onto a porous particulate carrier. 
     
     
         6 . The multi-layered pharmaceutical composition of  claim 5 , wherein the porous particulate carrier comprises microcrystalline cellulose. 
     
     
         7 . The multi-layered pharmaceutical composition of  claim 1 , wherein the multi-layered pharmaceutical composition comprises between two and ten layers. 
     
     
         8 . The multi-layered pharmaceutical composition of  claim 7 , wherein the multi-layered pharmaceutical composition comprises between two and five layers. 
     
     
         9 . The multi-layered pharmaceutical composition of  claim 1 , wherein the form of the pharmaceutical composition is a core formulation surrounded by one or more continuous layers or a core formulation coated by one or more discontinuous layers so as to form a layered or side-by-side configuration of the two or more formulations. 
     
     
         10 . The multi-layered pharmaceutical composition of  claim 1 , wherein the sugar substitute of the dissolvable formulation comprises isomalt and wherein the sugar alcohol syrup of the dissolvable follnulation comprises maltitol syrup. 
     
     
         11 .- 25  (canceled) 
     
     
         26 . The multi-layered pharmaceutical composition of  claim 1 , wherein the product comprises a combination of formulations selected from the group consisting of: formulations i) and ii); formulations i) and iii); formulations i) and iv); formulations i) and v); formulations i) and vi); formulations ii) and iii); formulations ii) and iv); formulations ii) and v); formulations ii) and vi).; formulations iii) and iv); formulations iii) and v); formulations iii) and vi); fon mlations iv) and v); formulations iv) and vi); formulations i), ii), and iii); formulations i), ii), and iv); formulations i), ii), and v); formulations i), ii), and vi); formulations i), iii), and iv); formulations i), iii), and v); formulations i), iii), and vi); formulations i), iv), and v); formulations i), iv), and vi); formulations i), v), and vi); formulations ii), iii), and iv); formulations ii), iii), and v); formulations ii), iii), and vi); formulations ii), iv), and v); formulations ii), iv), and vi); formulations ii), v), and vi); formulations iii), iv), and v); formulations iii), iv), and vi); and formulations iii), v), and vi). 
     
     
         27 . A process for preparing a multi-layered pharmaceutical composition, comprising:
 preparing a first formulation by combining one or more nicotinic compounds with one or more components selected from the group consisting of binders, lipid components, polysaccharide fillers, sugar substitutes, sugar alcohol syrups, flavorants, sweeteners, emulsifiers, disintegration aids, humectants, buffering agents, and mixtures thereof to form a first nicotinic compound-containing mixture and forming the first nicotinic compound-containing mixture into a desired form;   preparing a second formulation by combining one or more nicotinic compounds with one or more components selected from the group consisting of binders, lipid components, polysaccharide fillers, sugar substitutes, sugar alcohol syrups, flavorants, sweeteners, emulsifiers, disintegration aids, humectants, buffering agents, and mixtures thereof to form a second nicotinic compound-containing mixture and forming the second nicotinic compound-containing mixture into a desired form;   and applying the second formulation to the first formulation,   wherein the formulations are selected from the group consisting of:   i) a dissolvable formulation comprising a sugar substitute in an amount of at least about 80% by weight and a sugar alcohol syrup;   ii) a meltable formulation comprising a lipid having a melting point of about 36° C. to about 45° C.;   iii) a pastille formulation comprising a polysaccharide filler;   iv) a pastille formulation comprising a sugar alcohol and a natural gum binder component;   v) a chewable formulation comprising a binder, an emulsifier, and a lipid having a melting point of about 36° C. to about 45° C.; and   vi) a hard coating formulation comprising a binder, a sugar substitute, and a sugar alcohol syrup.   
     
     
         28 . The process of  claim 27 , wherein the first formulation is formed into a desired form by pouring the first nicotinic compound-containing mixture into a mold or injection molding the first nicotinic compound-containing mixture. 
     
     
         29 . The process of  claim 27 , wherein the second formulation is applied by spray coating, dip coating, or by forming the second formulation into a sheet that is applied to the first formulation as a sandwiched coating. 
     
     
         30 . The process of  claim 29 , wherein the spray coating or dip coating is conducted at a temperature such that the first formulation is maintained in substantially intact form. 
     
     
         31 . The process of  claim 27 , further comprising applying a third formulation as a coating on the second formulation. 
     
     
         32 . The process of  claim 31 , wherein the third formulation is applied by spray coating, dip coating, or by fanning the third formulation into a sheet that is applied to the second formulation as a sandwiched coating. 
     
     
         33 . 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. 
     
     
         34 . The method of  claim 33 , wherein said administering step comprises administering the pharmaceutical composition to a human subject as a smoking cessation aid.