NICOTINE LOZENGE FORMULATION
Aspects of the present invention are directed to a nicotine lozenge for oral administration comprising: a nicotine active; at least one high viscosity, water soluble, synthetic or semi-synthetic, non-ionic polymer; and at least one low viscosity, water soluble, synthetic or semi-synthetic, non-ionic polymer. Lozenges of the present invention are more stable and less expensive than traditional lozenges.
1 . A nicotine lozenge for oral administration comprising:
a nicotine active;
at least one high viscosity, water soluble, synthetic or semi-synthetic, non-ionic polymer; and
at least one low viscosity, water soluble, synthetic or semi-synthetic, non-ionic polymer.
2 . The lozenge of claim 1 , wherein the ratio of high viscosity water soluble, synthetic or semi-synthetic, non-ionic polymer to low viscosity water soluble, synthetic or semi-synthetic, non-ionic polymer is between about 1:50 and about 50:1.
3 . The lozenge of claim 2 , wherein the ratio of high viscosity water soluble, synthetic or semi-synthetic, non-ionic polymer to low viscosity water soluble, synthetic or semi-synthetic, non-ionic polymer is between about 1:2 and about 2:1.
4 . The lozenge of claim 1 , further comprising at least one alkaline buffering agent.
5 . The lozenge of claim 1 , wherein the nicotine active is nicotine polacrilex.
6 . The lozenge of claim 1 , wherein the high viscosity water soluble synthetic or semi-synthetic, non-ionic polymer is selected from the group consisting of alkylcelluloses, hydroxyalkylcelluloses, hydroxyalkyl alkylcelluloses, carboxyalkylcellulose esters, methacrylate copolymers, polyvinylalcohol, polyvinylpyrrolidone, copolymers of polyvinylpyrrolidone with vinyl acetate, combinations of polyvinylalcohol and polyvinylpyrrolidone, polyalkylene oxides, and copolymers of ethylene oxide and propylene oxide.
7 . The lozenge of claim 1 , wherein the low viscosity water soluble, synthetic or semi-synthetic, non-ionic polymer is selected from the group consisting of alkylcelluloses, hydroxyalkylcelluloses, hydroxyalkyl alkylcelluloses, carboxyalkylcellulose esters, methacrylate copolymers, polyvinylalcohol, polyvinylpyrrolidone, copolymers of polyvinylpyrrolidone with vinyl acetate, combinations of polyvinylalcohol and polyvinylpyrrolidone, polyalkylene oxides, and copolymers of ethylene oxide and propylene oxide.
8 . The lozenge of claim 1 , wherein the high viscosity water soluble, synthetic or semi-synthetic, non-ionic polymer has a viscosity of between about 2,000 cps to about 6,000 cps as measured by Brookfield type LV Model, or equivalent.
9 . The lozenge of claim 1 , wherein the low viscosity water soluble, synthetic or semi-synthetic, non-ionic polymer has a viscosity of between about 50 cps and about 150 cps as measured by Capillary Viscometer Methods 911.
10 . The lozenge of claim 6 , wherein the hydroxyalkyl alkylcellulose is hydroxypropylmethylcellulose.
11 . The lozenge of claim 7 , wherein the hydroxyalkyl alkylcellulose is hydroxypropylmethylcellulose.
12 . The lozenge of claim 4 , wherein the at least one alkaline buffering agent is selected from the group consisting of sodium carbonate, sodium bicarbonate, potassium phosphate, potassium carbonate and potassium bicarbonate.
13 . The lozenge of claim 1 , further comprising at least one dissolution modifier.
14 . The lozenge of claim 1 , further comprising at least one diluent.
15 . The lozenge of claim 1 , further comprising at least one excipient selected from the group consisting of taste masking agents, sweetening agents, flavorants, chelating agents, antioxidants, glidants, and colorants.
16 . A nicotine lozenge for oral administration comprising:
an intragranular component comprising a water soluble, synthetic or semi-synthetic, non-ionic polymer; and
an extragranular component comprising a nicotine active and at least one high viscosity water soluble, synthetic or semi-synthetic, non-ionic polymer and the at least one low viscosity water soluble, non-ionic, synthetic or semi-synthetic polymer.
17 . The lozenge of claim 16 , wherein the ratio of high viscosity water soluble, synthetic or semi-synthetic, non-ionic polymer to low viscosity water soluble, non-ionic, synthetic or semi-synthetic polymer is between about 1:50 and about 50:1.
18 . The lozenge of claim 17 , wherein the ratio of high viscosity water soluble, synthetic or semi-synthetic, non-ionic polymer to low viscosity water soluble, non-ionic, synthetic or semi-synthetic polymer is between about 1:2 and about 2:1.
19 . The lozenge of claim 16 , further comprising at least one alkaline buffering agent.
20 . The lozenge of claim 16 , wherein the nicotine active is nicotine polacrilex.
21 . The lozenge of claim 16 , wherein the high viscosity water soluble, synthetic or semi-synthetic, non-ionic polymer is selected from the group consisting of alkylcelluloses, hydroxyalkylcelluloses, hydroxyalkyl alkylcelluloses, carboxyalkylcellulose esters, methacrylate copolymers, polyvinylalcohol, polyvinylpyrrolidone, copolymers of polyvinylpyrrolidone with vinyl acetate, combinations of polyvinylalcohol and polyvinylpyrrolidone, polyalkylene oxides, and copolymers of ethylene oxide and propylene oxide.
22 . The lozenge of claim 16 , wherein the low viscosity water soluble, synthetic or semi-synthetic, non-ionic polymer is selected from the group consisting of alkylcelluloses, hydroxyalkylcelluloses, hydroxyalkyl alkylcelluloses, carboxyalkylcellulose esters, methacrylate copolymers, polyvinylalcohol, polyvinylpyrrolidone, copolymers of polyvinylpyrrolidone with vinyl acetate, combinations of polyvinylalcohol and polyvinylpyrrolidone, polyalkylene oxides, and copolymers of ethylene oxide and propylene oxide.
23 . The lozenge of claim 16 , wherein the high viscosity water soluble, synthetic or semi-synthetic, non-ionic polymer has a viscosity of between about 2,000 cps to about 6,000 cps as measured by Brookfield type LV Model, or equivalent.
24 . The lozenge of claim 16 , wherein the low viscosity water soluble, synthetic or semi-synthetic, non-ionic polymer has a viscosity of between about 50 cps and about 150 cps as measured by Capillary Viscometer Methods 911.
25 . The lozenge of claim 23 , wherein the hydroxyalkyl alkylcellulose is hydroxypropylmethylcellulose.
26 . The lozenge of claim 24 , wherein the hydroxyalkyl alkylcellulose is hydroxypropylmethylcellulose.
27 . The lozenge of claim 19 , wherein the at least one alkaline buffering agent is selected from the group consisting of sodium carbonate, sodium bicarbonate, potassium phosphate, potassium carbonate and potassium bicarbonate.
28 . The lozenge of claim 16 , further comprising at least one dissolution modifier.
29 . The lozenge of claim 16 , further comprising at least one diluent.
30 . The lozenge of claim 16 , further comprising at least one excipient selected from the group consisting of taste masking agents, sweetening agents, flavorants, chelating agents, antioxidants, glidants, and colorants.
31 . A lozenge of claim 16 , wherein the lozenge has an in vitro dissolution profile of the dissolution release ranges at various time points (as determined by USP Type I apparatus, basket, Phosphate buffer at pH 7.4, 37° C. set at rotating speed of 100 rpm) of:
25 to 50% at 1 hour;
50 to 99% at 3 hours;
75 to 100% at 6 hours.
32 . A lozenge of claim 16 , wherein the lozenge has an in vitro dissolution profile of the dissolution release ranges at various time points (as determined by USP Type I apparatus, basket, Phosphate buffer at pH 7.4, 37° C. set at rotating speed of 100 rpm) of:
30 to 40% at 1 hour;
50 to 70% at 3 hours;
90 to 100% at 6 hours.
33 . A lozenge of claim 16 , wherein the lozenge has an in vitro dissolution profile of the dissolution release ranges at various time points (as determined by USP Type I apparatus, basket, Phosphate buffer at pH 7.4, 37° C. set at rotating speed of 100 rpm) of:
33 to 37% at 1 hour;
65 to 70% at 3 hours;
97 to 100% at 6 hours.
34 . A lozenge of claim 16 comprising a median time to maximum plasma concentration of nicotine (T max ) from about 1.2 hours to about 2 hours after administration.
35 . A lozenge of claim 16 comprising a median time to maximum plasma concentration of nicotine (T max ) from about 1.3 hours to about 1.7 hours after administration.
36 . A lozenge of claim 16 comprising a median time to maximum plasma concentration of nicotine (T max ) from about 1.3 hours to about 1.5 hours after administration.
37 . A lozenge of claim 16 comprising a mean plasma concentration (C max ) of nicotine from about 16 ng/ml to about 20 ng/ml, based on administration.
38 . A lozenge of claim 16 comprising a mean plasma concentration (C max ) of nicotine from about 17 ng/ml to about 19 ng/ml, based on administration.
39 . A lozenge of claim 16 comprising a mean plasma concentration (C max ) of nicotine between 80% and 125% of the mean plasma concentration (C max ) of 18.67 ng/ml.
40 . A lozenge of claim 16 , wherein the lozenge provides a mean Area Under the Curve (AUC 0-12) of nicotine of between 80 and 100 ng*hr/mL.
41 . A lozenge of claim 16 , wherein the lozenge provides a mean Area Under the Curve (AUC 0-12) of nicotine of between 85 and 95 ng*hr/mL.
42 . A lozenge of claim 16 , wherein the lozenge provides a mean Area Under the Curve (AUC (0-12) ) of nicotine of between 80% and 125% of the mean Area Under the Curve (AUC (0-12) ) of 90 ng*hr/mL.
43 . A lozenge of claim 16 , wherein the lozenge is bioequivalent to the NICORETTE Original 4 mg lozenge.
44 . A lozenge of claim 16 , having a stability at a temperature of 40° C. and a relative humidity of 75% in a Duplex package of at least 6 months.
45 . The lozenge of claim 44 , wherein the lozenge is stable for at least 12 months.
46 . The lozenge of claim 44 , wherein the lozenge is stable for at least 24 months.