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1. WO2009072953 - PROCÉDÉ ET DISPOSITIF DE PRODUCTION DE PARTICULES AU MOYEN DE FLUIDES SUBCRITIQUES

Note: Texte fondé sur des processus automatiques de reconnaissance optique de caractères. Seule la version PDF a une valeur juridique

[ EN ]

C L A I M S
1. A method for producing a batch of particles of a substance (= particle-forming substance) in a production arrangement, said particles having predetermined sizes (primarily measured as mean particle diameter and/or size distribution) and/or morphology, comprising the steps of: i) mixing within a spray nozzle (101 ,201 ) and under flow conditions a stream of a liquid solution (102,202) in which the substance is dissolved or dispersed with a stream of a fluid (103,203), the kind solvent in the solution, the kind of fluid and the proportion of the volume of the solution relative to the volume of the fluid being selected to promote nucleation and particle formation of the substance in the mixture, and
ii) passing said mixture in the form of a spray (204) through a spray outlet (109,209,309) of the nozzle (101,201,301) into a particle collecting container, such as a chamber
(105,205), and
iii) separating and collecting within said container said particles from said mixture, characterized in that the solvent is a liquid and the fluid is an aqueous liquid in a subcritical state.

2. The method of claim 1, characterized in that said fluid and said solvent are miscible with each other.

3. The method of any of claims 1 -2, characterized in that the volumetric flow velocities of the solution stream (102,202,302) at the upstream end of the mixing arrangement (114,214,314) can be found in the interval of 0.01-20%, such as > 0.1 % or > 0.5 % or > 1 % and/or < 15 % < or < 10 % or < 5 %, of the of the flow velocity of the fluid stream (103,203,303).

4. The method of any of claims 1 -3, characterized in that the concentration of the particle- forming substance in the solution is below the saturation concentration of the substance, typically < 80 % and/or > 1 %, such as > 5 % or > 15 % or > 25 %, of the saturation concentration at the pressures and temperature applied at mixing.

5. The method of any of claims 1-4, characterized in that the pressure drop over the spray outlet of the nozzle is < 30 bar, such as < 20 bar, or < 10 bar.

6. The method of any of claims 1-5, characterized in that steps (i) and (ii) are performed in two or more separate spray nozzles (401a,b...) that belong to the production arrangement with at least two of the nozzles being in spray communication with the same particle collecting container (405).

7. The method of any of claims 1-6, characterized in that steps (i) and (ii) are performed in two or more separate spray nozzles (401a,b...) that belong to the production arrangement with two or more particle collecting containers (505a,b...) with every one of the containers (505a,b...) containing at least one nozzle (501a,b...).

8. The method of any of claims 6-7, characterized in that
a) said two or more nozzles are essentially identical and/or
b) running particle formation in at least two of said two or more nozzles simultaneously.

9. The method of any of claims 1-8, characterized in that the predetermined mean diameter of the particles of the batch are selected to be < 20 μm or < 10 μm and/or the size distribution of the particle in the batch is that 80 % of the particles have sizes with an interval having the width of < 30 μm.

10. The method of any of claims 1-9, characterized in that the mixing is initiated by merging the fluid stream and the solution stream at an angle selected in the interval of 0°-180°, with preference for 30°-150° and the absolute preference for 90° or 0°.

11. The method of any of claims 1-10, characterized in that
A) said nozzle (201,301) comprises
a) two internal transport conduits for the solution and the fluid, respectively
(202,203,203,303), which conduits are coaxial at least in their upstream parts, and in
their downstream ends (238,234) are merging with each other into
b) a mixing arrangement (214,314) followed by and/or coinciding with
c) a spray outlet (209,309), and
B) performing step (i) in said mixing arrangement and step (ii) in said spray outlet.

12. The method of claim 11 , characterized in that
a) the downstream part (238,342) of one of the two internal transport conduits
(210,212,310,312) is cylindrical providing for cylindrical flow at the position of merging with the other conduit, and 5 b) the downstream part (234,334) of the other one of conduits is disc-shaped providing an
annular flow that is directed radially outwards from a centre which coincides with the axis of the cylindrical flow, the merging angle between the two conduits being selected in the
interval of 30°-l 50°, and
b) the mixing arrangement (214,314) is annular comprising an annular upstream end at the 10 merging of the two internal transport conduits (210,212,310,312) and an annular
downstream end, and
c) the spray outlet (209) is annular and communicates in the upstream direction with the
annular downstream end of the mixing arrangement.

15 13. The method of claim 12, characterized in that the inner one (212) of the two coaxial internal transport conduits (210,212) is cylindrical in its downstream end (238) and the outer one
(210) is disc-shaped in its downstream end (234).

14. The method of claim 14, characterized in that the two internal coaxial transport conduits are 20 coaxial to their point of merging (to the point of mixing).

15. The method of any of claims 11-15, characterized in that the solution stream passes through the inner one (212,312) of the internal transport conduits (210,212,310,312) that are coaxial in their upstream end and the fluid stream through the outer one (210,310) of these conduits

25 (210,212,310,312).

16. The method of any one of claims 1-16, characterized in that the fluid stream at the position of mixing contains a make-up agent.

30 17. The method according to any of claims 1-17, characterized in that the substance is
pharmacologically active.

18. Pharmaceutical formulation comprising a therapeutically active ingredient possibly together with a vehicle, an additive etc, characterized in that at least one of the ingredients has been 35 used in the form of particles produced according to any of claims 1-18 during the
manufacture of the formulation.

19. A production arrangement suitable for production of particles from a solution that comprises a particle-forming substance dissolved or dispersed in a solvent by mixing the solution with a fluid acting as an atomizing and antisolvent agent, which arrangement comprises at least: a) a spray nozzle (101,201,301) having a fluid transport conduit (210,212,310,312), a
solution transport conduit (210,212,310,312), and a mixing arrangement (114,214,314) for mixing the fluid and the solution with each other downstream of the internal transport conduits (210,212,310,312), and a spray outlet (109,209,309),
b) a particle collecting chamber (105) in which the spray outlet (109) of the nozzle is placed and a function (115) for separating and collecting particles produced in the spray nozzle from the solution-fluid mixture, and
c) a transport conduit ( 116,216) external to the nozzle for transferring fluid ( 103 ,203) to fluid transport conduit (210,212,310,312) of the nozzle (101,201),
characterized in comprising
i) one or more inlet conduits for introducing a make-up agent and/or for recycling fluid used in the production (117,118 and 217,218, respectively) into the fluid stream
(103,203) into the production, i.e. at a position in the fluid stream upstream of the mixing arrangement (114,214), and/or
ii) two or more spray nozzles (401a,b..,501a,b...) with at least two (401a,b...) of them being placed in the same collecting chamber (405) and/or with at least two (501a,b...) of them being placed in different collecting chambers (505a,b...) each of which contains at least one, two or more spray nozzles, and/or
iii) a recycling function (118+119+120,218+219) for recycling fluid (106,206) used in the process into the fluid stream (103,203) via one of said inlet conduit (118,218), i.e. at a position upstream of the mixing arrangement (114,214).