NICOTINE PARTICLES AND COMPOSITIONS

Abstract

The composition is formed of a plurality of particles. These particles include nicotine, a sugar, and an amino acid or short peptide.

Claims

1. A powder composition comprising a plurality of particles comprising nicotine particles, the nicotine particles comprising: nicotine; a sugar; and an amino acid, wherein about 90% of the plurality of particles have a particle size of about 4.5 micrometres or less, and about 50% of the plurality of particles have a particle size of less than about 2.5 micrometres.

2. The powder composition of claim 1, wherein the amino acid comprises leucine, alanine, valine, isoleucine, methionine, phenylalanine, tyrosine, or tryptophan.

3. The powder composition of claim 1, wherein the amino acid consists of leucine.

4. The powder composition of claim 1, wherein the nicotine comprises a nicotine salt.

5. The powder composition of claim 4, wherein the nicotine salt is a salt of nicotine base and levulinic acid, citric acid, gluconic acid, benzoic acid, propionic acid, butyric acid, sulfosalicylic acid, maleic acid, lauric acid, malic acid, fumaric acid, succinic acid, tartaric acid, amsonic acid, pamoic acid, mesylic acid, aspartic acid, formic acid, acetic acid, propionic acid, succinic acid, camphorsulfonic acid, fumaric acid, isethionic acid, lactic acid, mucic acid, para-toluenesulfonic acid, glycolic acid, glucuronic acid, furoic acid, glutamic acid, benzoic acid, anthranilic acid, salicylic acid, phenylacetic acid, pyruvic acid, mandelic acid, embonic (pamoic), methanesulfonic acid, ethanesulfonic acid, pantothenic acid, benzenesulfonic (besylate), stearic acid, sulfanilic acid, alginic acid, galacturonic acid, or a combination thereof.

6. The powder composition of claim 1, wherein the nicotine particles comprise from 5 wt % to 15 wt % nicotine.

7. The powder composition of claim 1, wherein the nicotine particles comprise from 60 wt % to 95 wt % sugar.

8. The powder composition of claim 1, wherein the nicotine particles comprise from 70 wt % to 90 wt % sugar.

9. The powder composition of claim 1, wherein about 10 vol % of the nicotine particles are below 0.82 μm in size.

10. The powder composition of claim 1, wherein about 50 vol % of the nicotine particles are below 2.1 μm in size.

11. The powder composition of claim 1, wherein about 90 vol % of the nicotine particles are below 4.1 μm in size.

12. The powder composition of claim 1, wherein the nicotine particles are substantially within a range of 0.5 μm to 4.2 μm in size.

13. The powder composition of claim 1, wherein the nicotine particles are prepared by spray drying a flowable liquid composition comprising the nicotine and a liquid carrier.

14. The powder composition of claim 13, wherein the nicotine particles are prepared at a temperature of 50° C. to 85° C.

15. The powder composition of claim 1 further comprising menthol.

Description

[0049] FIG. 1 is a schematic flow diagram of an illustrative method 100 of forming the particles 125. The method 100 includes combining nicotine 102, a sugar 104, and an amino acid or peptide 106 in a liquid carrier to form a liquid mixture 115 at block 110. Then, at block 120, the liquid mixture 115 is spray dried to form a plurality of particles 125.

EXAMPLES

[0050] All the examples (except Table 3 examples) are formulated by combining a nicotine free base and an acid in water (at the specified ratio) to form a stable nicotine salt solution. Then the sugar and amino acid (leucine) is combined with the nicotine salt solution to form a liquid mixture. Then the liquid mixture is atomized and dried to form dry particles that are collected to from the composition.

[0051] The Table 3 examples are formulated by combining a nicotine free base with sugar and an amino acid (leucine) to form a liquid mixture. Then the liquid mixture is atomized and dried to form dry particles that are collected to from the composition.

[0052] The spray dryer was a Buchi B-290 spray dryer (available from Buchi Corp., DE, USA). The liquid mixture was provided to the spray dryer at a flow rate of 2 ml/min at 5 bar atomization pressure. The outlet temperature was about 80 degrees Celsius for examples utilizing trehalose. Table 1 below describes lactic acid formulations. Table 2 below describes pyruvic acid formulations. Table 3 below describes no acid formulations. Table 4 and Table 5 report the particle size distribution of various examples.

TABLE-US-00001 TABLE 1 Lactic Acid Nicotine Powder Formulations pH of powder Example Formulation solution Comments L1 10% Nicotine, Lactic acid (1:1), 7.3 Small amount of powder adhering 85% Trehalose to spray dryer surface L2 15% Nicotine, Lactic acid (1:1), 7.0 Small amount of powder adhering 77% Trehalose to spray dryer surface L3 10% Nicotine, Lactic acid (1:1), 7.5 Free flowing powder-no 80% Trehalose, 5% Leucine adherence L4 15% Nicotine, Lactic acid (1:1), 7.1 Free flowing powder-no 72% Trehalose, 5% Leucine adherence L5 20% Nicotine, Lactic acid (1:1), — Free flowing powder-no 64% Trehalose, 5% Leucine adherence

TABLE-US-00002 TABLE 2 Pyruvic Acid Nicotine Powder Formulations pH of powder Example Formulation solution Comments P1 10% Nicotine, Pyruvic acid (0.6:1), 7.5 Powder adhering to spray dryer 87% Trehalose surface, cohesive powder P2 15% Nicotine, Pyruvic acid (0.6:1), 7.8 Cohesive powder, some static 80% Trehalose charge P3 10% Nicotine, Pyruvic acid (0.6:1), 7.7 Free flowing powder-no 82% Trehalose, 5% Leucine adherence, some static charge P4 15% Nicotine, Pyruvic acid (0.6:1), 7.8 Free flowing powder-no 75% Trehalose, 5% Leucine adherence P5 20% Nicotine, Pyruvic acid (0.6:1), 7.7 Free flowing powder-no 68% Trehalose, 5% Leucine adherence

TABLE-US-00003 TABLE 3 No Acid (Free Base) Nicotine Powder Formulations pH of powder Example Formulation solution Comments N1 10% Nicotine, 90% Trehalose 9.3 Some powder adhering to spray dryer surface N2 15% Nicotine, 85% Trehalose 9.5 Some powder adhering to spray dryer surface N3 10% Nicotine, 85% Trehalose, 5% 8.6 Free flowing powder-no Leucine adherence, some static charge N4 15% Nicotine, 80% Trehalose, 5% 8.7 Free flowing powder-no Leucine adherence N5 20% Nicotine, 75% Trehalose, 5% 8.8 Free flowing powder-no Leucine adherence

TABLE-US-00004 TABLE 4 Particle Size Distribution—reported in micrometres Example X.sub.10 X.sub.50 X.sub.90 VMD L1 0.65 1.43 3.54 1.81 L2 0.68 1.62 3.75 1.97 L3 0.76 1.89 3.86 2.14 L4 0.92 2.14 3.99 2.35 L5 0.78 1.95 3.90 2.19 P1 0.67 1.54 3.47 1.85 P2 0.67 1.53 3.54 1.86 P3 0.66 1.48 3.54 1.84 P4 0.72 1.78 3.79 2.06 P4 0.65 1.43 3.54 1.81 N1 0.68 1.62 3.75 1.97 N2 0.76 1.89 3.86 2.14 N3 0.92 2.14 3.99 2.35 N4 0.78 1.95 3.90 2.19 N5 0.67 1.54 3.47 1.85
X.sub.10 refers to size of particle where 10% of particles, by volume, are less than this size.
X.sub.50 refers to size of particle where 50% of particles, by volume, are less than this size.
X.sub.90 refers to size of particle where 90% of particles, by volume, are less than this size.
VMD refers to volume mean diameter.

TABLE-US-00005 TABLE 5 Further Formulations Example Formulation X.sub.10 X.sub.50 X.sub.90 VMD MMAD 1 10% Nicotine, Lactic Acid (1:1), 0.92 2.17 4.15 2.4 3.8 80% Trehalose, 5% Leucine 2 10% Nicotine, Pyruvic Acid (1:0.6), 1.04 2.56 5.08 2.9 4.0 82% Trehalose, 5% Leucine 3 10% Nicotine, Citric Acid (1:0.25), 0.81 2.34 5.48 2.8 3.5 82% Trehalose, 5% Leucine 4 10% Nicotine, Aspartic Acid (1:0.6), 0.82 2.24 4.96 2.6 4.2 80% Trehalose, 5% Leucine 5 5% Nicotine, Lactic Acid (1:1), 0.7 1.5 3.0 1.5 2.5 82% Trehalose, 10% Leucine