Preparation of nanoparticles
View Patent ↗Nanoparticles of a deposited bioactive agent can be obtained by selecting a solvent composition, selecting a deposition substrate, preparing a solution of the bioactive agent in the solvent composition, and applying the solution to a substrate as a plurality of droplets, such that evaporation of the applied solution produces nanoparticles of the bioactive agent.
1. A method of preparing nanoparticles of a bioactive agent, comprising:
selecting a solvent composition;
selecting a deposition substrate;
preparing a solution of the bioactive agent in the solvent composition; and
applying the solution to the substrate as a plurality of droplets;
wherein evaporation of the applied solution on the substrate produces nanoparticles containing the bioactive agent; and
wherein the bioactive agent is selected from the group consisting of glyburide, digoxin, prednisolone, lovastatin, and indomethacin.
2. The method of claim 1 , wherein the solvent composition includes at least two solvent components.
3. The method of claim 2 , wherein bioactive agent has a differential solubility in the at least two solvent components.
4. The method of claim 2 , wherein the two solvent components each have a dielectric constant between about 2 and about 40, and each have a boiling point below 90° C.
5. The method of claim 1 , wherein the solution includes at least one solvent selected from the group consisting of chloroform, tetrabromoethane, tetrachloroethylene, trichlorethylene, trichloroacetic acid, trichloroethane, 1,2-dichloroethane, trichloroethylene, bromoform, tetrahydrofuran, and toluene; and at least one solvent selected from the group consisting of ethanol, propanol, isopropanol, butanol, and isobutanol.
6. The method of claim 1 , wherein the solvent composition includes ethanol and chloroform.
7. The method of claim 6 , wherein the solvent composition includes ethanol and chloroform in a ratio of about 80:20.
8. The method of claim 1 , wherein the solvent composition includes ethanol and chloroform in a ratio of between about 70:30 and 90:10.
9. The method of claim 1 , wherein the substrate is selected to have a substantially nonpolar surface character.
10. The method of claim 9 , wherein the substrate includes a fluorinated polymer.
11. The method of claim 9 , wherein the deposition substrate includes paraffin.
12. The method of claim 1 , wherein the substrate is selected to have a substantially impermeant surface character.
13. The method of claim 1 , wherein applying the solution to the substrate includes ejecting droplets of the solution with a thermal ejection element.
14. The method of claim 1 , wherein applying the solution to the substrate includes ejecting droplets of a glyburide solution with a piezoelectric ejection element.
15. The method of claim 1 , wherein the solution includes at least one additive.
16. The method of claim 15 , wherein the additive is a polymer additive.
17. The method of claim 1 , wherein the resulting nanoparticles are substantially amorphous.
18. The method of claim 1 , wherein the resulting particles are substantially spherical.
19. The method of claim 1 , wherein the particles have an average size of less than about 1 μm.
20. The method of claim 1 , wherein the bioactive agent is glyburide.
21. The method of claim 1 , wherein the bioactive agent is digoxin.
22. The method of claim 1 , wherein the bioactive agent is prednisolone.
23. A method of preparing amorphous nanoparticles of a bioactive agent, the method comprising:
preparing a solution of a bioactive agent that is glyburide, digoxin, prednisolone, lovastatin, or indomethacin in a composition of ethanol and chloroform; and
applying the solution to a substantially impermeant substrate as a plurality of droplets;
wherein evaporation of the applied bioactive agent solution produces at least substantially amorphous nanoparticles of the bioactive agent.
24. The method of claim 23 , wherein the solution includes a polymer additive.