Method for formulating large diameter synthetic membrane vesicles

• US 9,808,424 B2
• Filed: 03/08/2013
• Issued: 11/07/2017
• Est. Priority Date: 04/09/2010
• Status: Active Grant

• Current Assignee: Pacira Pharmaceuticals, Inc. (Pacira Biosciences, Inc.)
• Original Assignee: Pacira Pharmaceuticals, Inc. (Pacira Biosciences, Inc.)
• Inventors: Schutt, Ernest George, McGuire, Ronald Warren, Walters, Peter Andrew, Los, Kathleen D. A.
• Primary Examiner(s): Hindenlang, Alison L
• Assistant Examiner(s): Moreno Hernandez, Jerzi H
• Application Number:
  US13/791,569
• Publication Number:
  US 20130183375A1
• Time in Patent Office: 1,705 Days
• CPC Class Codes: A61K 31/445 Non condensed piperidines, e.g. piperocaine
• CPC Class Codes: A61K 31/4458 only substituted in position 2, e.g. methylphenidate
• CPC Class Codes: A61K 9/127 Liposomes
• CPC Class Codes: A61K 9/1271 Non-conventional liposomes, e.g. PEGylated liposomes, liposomes coated with polymers liposome as conjugate A61K47/6911
• CPC Class Codes: A61K 9/1277 Processes for preparing; Proliposomes
• CPC Class Codes: A61K 9/4833 Encapsulating processes; Filling of capsules mechanical aspects A61J3/07
• CPC Class Codes: A61M 11/00 Sprayers or atomisers specially adapted for therapeutic purposes in general B05B; aerosol containers B65D83/14
• CPC Class Codes: A61P 23/00 Anaesthetics
• CPC Class Codes: A61P 23/02 Local anaesthetics
• CPC Class Codes: B01D 1/16 by spraying B01D1/22 takes precedence
• CPC Class Codes: B01F 2035/98 Cooling
• CPC Class Codes: B01F 2101/22 Mixing of ingredients for pharmaceutical or medical compositions
• CPC Class Codes: B01F 23/2132 using nozzles
• CPC Class Codes: B01F 23/41 Emulsifying
• CPC Class Codes: B01F 23/49 Mixing systems, i.e. flow charts or diagrams
• CPC Class Codes: B01F 25/52 with a rotary stirrer in the recirculation tube
• CPC Class Codes: B01F 27/27 Mixers with stator-rotor systems, e.g. with intermeshing teeth or cylinders or having orifices the stirrers having a central axial inflow and a substantially radial outflow B01F27/81
• CPC Class Codes: B01F 35/92 for heating the outside of the receptacle, e.g. heated jackets or burners
• CPC Class Codes: B01J 13/043 Drying and spraying
• CPC Class Codes: B01J 13/125 by evaporation of the solvent apparatus therefor B01J13/043

Abstract

The present invention generally relates to the field of pharmaceutical sciences. More specifically, the present invention includes apparatus and devices for the preparation of pharmaceutical formulations containing large diameter synthetic membrane vesicles, such as multivesicular liposomes, methods for preparing such formulations, and the use of specific formulations for therapeutic treatment of subjects in need thereof. Formation and use of the pharmaceutical formulations containing large diameter synthetic membrane vesicles produced by using the apparatus and devices for therapeutic treatment of subjects in need thereof is also contemplated.

Claims

1. An evaporation apparatus, comprising at least one atomizing nozzle apparatus and a solvent removal vessel having a top, a bottom and a circular wall for removing an organic solvent from a droplet,

wherein the circular wall has a central axis;

wherein at least one atomizing nozzle apparatus comprises;

a first fluid conduit and a second fluid conduit each having at least one entrance orifice and at least one exit orifice;

a fluid contacting chamber having a top comprising at least one entrance orifice and having a bottom comprising at least one exit orifice and connecting to the at least one exit orifice of the first fluid conduit and the at least one exit orifice of the second fluid conduit; and

a third fluid conduit having at least one entrance orifice and at least one exit orifice, wherein the third fluid conduit annularly surrounds a portion of the fluid contacting chamber, and

wherein the solvent removal vessel comprises;

a carrier gas entrance orifice;

a solvent removal gas exit orifice centrally connected to the top and comprising a gas outlet tube extending into the solvent removal vessel residing along the central axis, wherein the solvent removal gas exit orifice diameter is less than 1/10 of a diameter of the inside of the solvent removal vessel wall and the gas outlet tube is fitted with a narrowing cone and optionally an annular ring; and

a product exit orifice connected to the bottom of the solvent removal vessel.

2. The evaporation apparatus of claim 1, wherein the at least one exit orifice of the fluid contacting chamber and the at least one exit orifice of the third fluid conduit are flush.

3. The evaporation apparatus of claim 1, wherein the at least one exit orifice of the fluid contacting chamber is recessed within the at least one exit orifice of the third fluid conduit.

4. The evaporation apparatus of claim 1, wherein the at least one exit orifice of the fluid contacting chamber extends beyond the at least one exit orifice of the third fluid conduit.

5. The evaporation apparatus of claim 1, wherein the first fluid conduit and the second fluid conduit are co-axial for a first portion of the first fluid conduit length.

6. The evaporation apparatus of claim 1, wherein the second fluid conduit annularly surrounds a second portion of the first fluid conduit.

7. The evaporation apparatus of claim 1, wherein a diameter of the fluid contacting chamber is larger than a diameter of the first fluid conduit.

8. The evaporation apparatus of claim 1, wherein the fluid contacting chamber conically narrows in diameter from the top of the fluid contacting chamber to the bottom of the fluid contacting chamber.

9. The evaporation apparatus of claim 1, wherein the fluid contacting chamber conically narrows in diameter from a point below the top of the fluid contacting chamber to the bottom of the fluid contacting chamber.

10. The evaporation apparatus of claim 1, wherein the at least one exit orifice of the first fluid conduit and the at least one exit orifice of the second fluid conduit are flush with each other.

11. The evaporation apparatus of claim 1, wherein the atomizing nozzle is mounted to and extending through the top of the solvent removal vessel.

12. The evaporation apparatus of claim 1, further comprising a rinse nozzle mounted to and extending through the top of the solvent removal vessel.

13. The evaporation apparatus of claim 1, wherein the ratio of the inside diameter of the solvent removal vessel to the diameter of the narrowing cone of the solvent removal gas exit orifice is between approximately 5:

1 and 100;

1.

14. The evaporation apparatus of claim 1, wherein the ratio of the inside diameter of the solvent removal vessel to the diameter of the narrowing cone of the solvent removal gas exit orifice is between approximately 20:

1 and 60;

1.

15. The evaporation apparatus of claim 1, wherein the gas outlet tube is fitted with the narrowing cone and the annular ring.