Synthesis of lysine acetylsalicylate glycine particles

1. A method for the production of lysine acetylsalicylate.glycine comprising the steps:

a) providing a solution of acetylsalicylic acid in ethanol;

b) providing an aqueous solution of lysine;

c) combining the solutions of step a) and b) to form a mixture;

d) optionally stirring the mixture;

e) adding acetone to the mixture;

f) incubating the mixture, to allow the formation of a acetylsalicylic acid lysinate product;

g) isolating the acetylsalicylic acid lysinate product;

wherein acetylsalicylic acid is used in excess compared to lysine and

wherein no seed crystals are added to the mixture;

h) providing a recrystallized glycine; wherein the glycine has been recrystallized with the following steps:

h1) dissolving glycine in water;

h2) adding acetone to the glycine solution;

h3) stirring the mixture until a precipitate is obtained;

i) combining the recrystallized glycine of step h) with the acetylsalicylic acid lysinate product of step g) to obtain lysine acetylsalicylate.glycine (LASAG) particles.

2. The method according to claim 1 , wherein the particles obtained in step i) have a median particle size of less than 40 μm, and wherein at least 90% of the particles obtained in step i) have a particle size of less than 110 μm.

3. The method according to claim 1 , wherein at least method steps c) to f) and/or h) and i) are performed at room temperature or below.

4. The method according to claim 1 , wherein the incubation step f) is performed at 10° C. or less.

5. The method according to claim 1 , wherein the isolation in step g) is performed by filtration.

6. The method according to claim 1 , wherein the isolation in step g) is performed by centrifugation.

7. The method according to claim 1 , wherein the solution of acetylsalicylic acid provided in step a) comprises about 8 to 12% (w/v), preferably about 9 to 10% (w/v) acetylsalicylic acid.

8. The method according to claim 1 , wherein the aqueous solution of lysine provided in step b) comprises about 30 to 35% (w/v) lysine.

9. The method according to claim 1 , wherein the aqueous solution of lysine provided in step b) further comprises dissolved glycine, and wherein the concentration of the glycine in the solution is optionally from 2 to 20% (w/v).

10. The method according to claim 1 , wherein the aqueous solution of lysine provided in step b) was prepared from lysine monohydrate.

11. The method according to claim 1 , wherein acetylsalicylic acid and lysine are used at a molar ratio of 1 to 0.9, or at a ratio of 1 to 0.95.

12. The method according to claim 1 , additionally comprising the step:

g1) washing the isolated product.

13. The method according to claim 12 , wherein the washing step involves washing the product with acetone.

14. The method according to claim 1 , wherein the method is performed under sterile conditions.

15. The method according to claim 1 , wherein the method is performed under non-sterile conditions and comprises the additional step:

j) sterilizing the product by irradiation.

16. A lysine acetylsalicylate.glycine obtainable by a method according to claim 1 , wherein the lysine acetylsalicylate.glycine particles have a median particle size of less than 100 μm.

17. The lysine acetylsalicylate.glycine according to claim 16 , wherein the lysine acetylsalicylate.glycine particles have a median particle size of less than 80 μm.

18. The lysine acetylsalicylate.glycine according to claim 16 , wherein the lysine acetylsalicylate.glycine particles have a median particle size of less than 50 μm.