Development of method and apparatus for producing lipid particles having desired particle diameter

1. A method of manufacturing a lipid particle with a desired particle size, the method comprising:

(A) preparing a primary diluting solution by mixing a first solution comprising a lipid and alcohol with a second solution comprising water in a first mixing region;

(B) supplying the primary diluting solution from the first mixing region to a second mixing region through a liquid supplying tube in a predetermined time; and

(C) preparing a secondary diluting solution by mixing the primary diluting solution with a third solution comprising water in the second mixing region;

wherein steps (A) to (C) are performed sequentially, and

wherein a particle size of a lipid particle is controlled by adjusting at least one condition including the predetermined time

wherein the lipid particle is further loaded with a drug, and wherein the method further comprises, before step (A):

(A-1) measuring a chronological change in a particle size of a lipid particle loaded with the drug under a condition where the concentration of the alcohol is constant;

wherein at least one condition required for adjusting the desired particle size including the predetermined time is determined based on information obtained by step (A-1).

2. The method of claim 1 , wherein the particle size of the lipid particle is controlled by further adjusting at least one condition selected from the group consisting of a concentration of the alcohol, a concentration of the lipid, and a temperature upon the mixing.

3. The method of claim 1 , the predetermined time is adjusted in the range of 0.1 to 60 minutes.

4. The method of claim 1 , which manufactures lipid particles with a particle size distribution with a PDI of less than 0.1.

5. The method of claim 1 , wherein the adjusting the predetermined time comprises selecting a tube having a predetermined length as the liquid supplying tube.

6. The method of claim 5 , wherein the length of the liquid supplying tube is adjusted between 10 m to 40 m.

7. The method of claim 1 , wherein the adjusting the predetermined time comprises adjusting flow rate in the liquid supplying tube.

8. The method of claim 1 , wherein the lipid particle is a liposome or a micelle.

9. The method of claim 1 , wherein the method further comprises, before step (A):

(A-2) measuring a particle size of a lipid particle formed when a concentration of the alcohol is changed by diluting a solution comprising the drug, the lipid, and the alcohol;

wherein the at least one condition required for adjusting the desired particle size selected from the group consisting of the concentration of the alcohol in the primary diluting solution, the concentration of the lipid, the predetermined time, and the temperature upon the mixing is determined based on information obtained by step (A-2) together with the information obtained by step (A-1).

10. The method of claim 1 , wherein the alcohol concentration in the primary diluting solution is adjusted to 18 wt % or greater.

11. The method of claim 1 , wherein steps (A) to (C) are performed in a closed system.

12. The method of claim 1 , wherein additional particle size controlling processing is not performed after step I.

13. The method of claim 1 , wherein a pressure in the liquid supplying tube is 1 Mpa or greater.

14. The method of claim 1 , wherein the secondary diluting solution is further supplied to a hollow fiber membrane column.