Device and method for encapsulation of hydrophilic materials

Patent metadata

Field	Value
Publication number	US-9308172-B2
Application number	US-201314062236-A
Country	US
Kind code	B2
Filing date	Oct 24, 2013
Priority date	Oct 26, 2012
Publication date	Apr 12, 2016
Grant date	Apr 12, 2016

Abstract

A process for preparing polymeric composite particles includes the steps of preparing an oil phase containing a biodegradable polymer and a water phase containing a hydrophilic compound or nanoparticle and emulsifying the oil phase in the water phase to form emulsions. Then solvent is removed from the emulsions to prepare the particles in the form of capsules and spheres in sizes from 0.01 μm (10 nm) to 50 μm.

First claim

What is claimed is:

1. A method of encapsulating a hydrophilic ingredient in nano- or micro-particles comprising a hydrophobic biodegradable polymer to make a polymeric composite, the method comprising:
preparing an organic phase comprising the biodegradable polymer and a solvent;
preparing a water phase comprising the hydrophilic ingredient, water, and a surfactant;
combining the organic phase and the water phase in a single step under emulsification conditions that form a W/O/W emulsion, wherein the emulsification conditions include running at a Reynolds number higher than 2300; and
removing the solvent from the W/O/W emulsion to harden the polymeric composites, wherein the solvent is not miscible in water, and wherein the ingredient is more highly soluble in water than in the solvent.

2. A method according to claim 1 , wherein the organic phase is saturated in water and the water phase is saturated in solvent.

3. A method according to claim 1 , wherein the solvent is selected from dichloromethane, methylene chloride, methyl ethyl ketone, ethyl acetate, chloroform, dichloroethane, and carbon tetrachloride.

4. A method according to claim 1 , wherein the emulsification conditions include operating at a shear rate of about 12,500 s −1 .

5. A method according to claim 1 , wherein the emulsification conditions include running at a Reynolds number higher than 4000.

6. A method according to claim 1 , wherein the emulsification conditions include mixing the organic phase and water phase in a Taylor-Couette mixer.

7. A method according to claim 1 , wherein the mixed phases contain an effective amount of a thickener molecule that is soluble in water, wherein the effective amount is sufficient to raise the viscosity to a level where the mixing occurs in a turbulent regime in a modified Taylor-Couette mixer.

8. A method according to claim 1 , wherein the hydrophilic ingredient is selected from peptides, proteins, and nucleic acids.

9. A method according to claim 1 , wherein the hydrophilic ingredient is selected from RNA and DNA.

10. A method according to claim 1 , wherein the hydrophilic ingredient is selected from cellulose nanowhiskers and microfibrils.

11. A method according to claim 1 , wherein the hydrophilic ingredient is selected from metallic nanoparticles, organic nanoparticles, and inorganic nanoparticles.

12. A method according to claim 1 , wherein the biodegradable polymer is selected from poly(L-lactic acid), poly(D,L-lactic acid), poly(glycolic acid), and poly(lactide-co-glycolide).

13. A method according to claim 1 , wherein the solvent is removed by diffusion.

14. A method according to claim 7 , wherein the thickener is selected from natural gums, cellulose derivatives, sugars, polymers, and clays.

15. A method of making a nanocomposite comprising cellulose nanowhiskers or cellulose microfibrils and a biodegradable polymer selected from poly(L-lactic acid), poly(D,L-lactic acid), poly(glycolic acid), poly(lactide-co-glycolide), the method comprising encapsulating the nanowhiskers or microfibrils in the biodegradable polymer using a one-step emulsion process comprising:
preparing an organic phase comprising the biodegradable polymer and a solvent;
preparing a water phase comprising the nanowhiskers or microfibrils, water, and a surfactant;
combining the organic phase and the water phase in a single step under emulsification conditions that form a W/O/W emulsion, wherein the emulsification conditions include running at a Reynolds number higher than 2300; and
removing the solvent from the W/O/W emulsion,

wherein the solvent is not miscible in water.

16. A method according to claim 15 , wherein the organic phase is saturated in water and the water phase is saturated in solvent.

17. A method according to claim 15 , wherein the solvent is selected from dichloromethane, methylene chloride, methyl ethyl ketone, ethyl acetate, chloroform, dichloroethane, and carbon tetrachloride.

18. A method according to claim 15 , wherein the emulsification conditions include operating at a shear rate of about 12,500 s −1 .

19. A method according to claim 15 , wherein the emulsification conditions include running at a Reynolds number higher than 4000.

20. A method according to claim 15 , wherein the emulsification conditions include mixing the organic phase and water phase in a Taylor-Couette mixer.

21. A method according to claim 15 , wherein the mixed phases contain an effective amount of a thickener molecule that is soluble in water, wherein the effective amount is sufficient to raise the viscosity to a level where the mixing occurs in a turbulent regime in a Taylor-Couette mixer.

22. A method according to claim 14 , wherein the thickener is selected from natural gums, acacia, tragacanth, alginic acid, carrageenan, locust bean gum, guar gum, and gelatin.

23. A method according to claim 14 , wherein the thickener is selected from cellulose derivatives, sodium carboxymethylcellulose, methyl cellulose, hydroxyethyl cellulose, and hydroxypropyl methyl cellulose.

24. A method according to claim 14 , wherein the thickener is selected from sugars, glucose, and fructose.

25. A method according to claim 14 , wherein the thickener is selected from polymers, polyvinyl alcohol, and polyvinyl pyrrolidone.

26. A method according to claim 14 , wherein the thickener is selected from clays and bentonite.

Assignees

• Univ Michigan State

Inventors

• Lee Ilsoon
• Ji Shaowen

Classifications

• A61K31/7105

  Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links · CPC title

• A61K31/711

  Natural deoxyribonucleic acids, i.e. containing only 2'-deoxyriboses attached to adenine, guanine, cytosine or thymine and having 3'-5' phosphodiester links · CPC title

• A61K9/1694

  resulting in granules or microspheres of the matrix type containing more than 5% of excipient · CPC title

• A61K9/1647 Primary

  Polyesters, e.g. poly(lactide-co-glycolide) · CPC title