Physically and chemically stable nicotine-containing particulate material
A nicotine-containing particulate material for release of nicotine, the material comprising a combination of nicotine or a pharmaceutically acceptable salt, complex or solvate thereof and a microcrystalline cellulose, The particulate material is stable upon storage and releases nicotine relatively fast. The particulate material can be used in the manufacture of nicotine-containing pharmaceutical composition, wherein the release of nicotine can be designed to be relatively fast so as to obtain a fast onset of action.
1. A method for preparing a nicotine-containing particulate material comprising combining a crystalline cellulose with nicotine or a pharmaceutically acceptable salt, complex, or solvate thereof dissolved in a hydrophilic solvent comprising an alcohol or a combination thereof with water such that the nicotine is at least partially retained inside voids of the crystalline cellulose, wherein the nicotine or a pharmaceutically acceptable salt, complex, or solvate thereof is dissolved in the hydrophilic solvent before combining with the crystalline cellulose, and wherein the crystalline cellulose comprises particles with a mean size range of about 15 to about 250 μm.
2. The method according to claim 1 , wherein the crystalline cellulose comprises microcrystalline cellulose (MCC).
3. The method according to claim 1 , wherein the nicotine is sorbed in pores present in the crystalline cellulose.
4. The method according to claim 1 , wherein the hydrophilic solvent comprises ethanol.
5. The method according to claim 1 , wherein the prepared nicotine-containing particulate material comprises nicotine or a pharmaceutically acceptable salt, complex, or solvate thereof at a concentration of at the most about 20% w/w, said concentration being calculated as the nicotine base.
6. The method according to claim 5 , wherein the prepared nicotine-containing particulate material comprises nicotine or a pharmaceutically acceptable salt, complex, or solvate thereof at a concentration of at the most about 7.5% w/w, said concentration being calculated as the nicotine base.
7. The method according to claim 1 , wherein combining comprises mixing in a high shear mixer.
8. The method according to claim 1 , comprising drying the combined crystalline cellulose and nicotine or a pharmaceutically acceptable salt, complex, or solvate thereof.
9. The method according to claim 8 , wherein after drying, the prepared nicotine-containing particulate material is stable for at least 14 weeks when stored openly at 40° C. and 50% relative humidity.
10. The method according to claim 1 , comprising coating at least a portion of the nicotine-containing particulate material.
11. The method according to claim 1 , wherein the prepared nicotine-containing particulate material, when tested in an in vitro dissolution test, releases at least 90% w/w of the nicotine or the pharmaceutically acceptable salt, complex or solvate thereof within, at the most, about 30 minutes.
12. A method for preparing a nicotine-containing particulate material comprising:
dissolving nicotine or a pharmaceutically acceptable salt, complex, or solvate thereof in a hydrophilic solvent comprising an alcohol or a combination thereof with water;
combining the resultant solution with microcrystalline cellulose (MCC) in a high shear mixer, the MCC comprising particles with a mean size range of about 15 to about 250 μm; and
drying the combination to form MCC particles having nicotine or a pharmaceutically acceptable salt, complex, or solvate thereof at a concentration of at the most about 7.5% w/w, said concentration being calculated as the nicotine base, at least partially retained inside voids of the MCC;
wherein the dried combination is stable for at least 14 weeks when stored openly at 40° C. and 50% relative humidity.