Method for formulating large diameter synthetic membrane vesicles

Patent metadata

Field	Value
Publication number	US-9724302-B2
Application number	US-201313786378-A
Country	US
Kind code	B2
Filing date	Mar 5, 2013
Priority date	Apr 9, 2010
Publication date	Aug 8, 2017
Grant date	Aug 8, 2017

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.

First claim

What is claimed is:

1. A continuous processing system, comprising:
a first concentrator unit comprising:
a first retentate vessel;
a first particle suspension inlet line, connected to the first retentate vessel;
a first outlet line, connecting the first retentate vessel and a first hollow fiber tangential flow filter;
a first solution inlet line;
a first sterilizing hydrophilic filter, connecting the first retentate vessel and the first solution inlet line;
a first pump located along the first outlet line between the first retentate vessel and the first hollow fiber tangential flow filter;
a second outlet line, leading to a second concentrator unit,

said second concentrator unit comprising:
a second retentate vessel;
a second particle suspension inlet line, connected to the second retentate vessel and the second outlet line;
a third outlet line, connecting the second retentate vessel and a second hollow fiber tangential flow filter;
a second solution inlet line;
a second sterilizing hydrophilic filter, connecting the second retentate vessel and the second solution inlet line; and
a second pump located along the third outlet line between the second retentate vessel and the second hollow fiber tangential flow filter.

2. The system of claim 1 , further comprising a new suspending medium inlet line connected to the first retentate vessel.

3. The system of claim 1 , wherein the continuous processing system is a continuous-flow particle-concentration system or continuous phase exchange system.

4. The system of claim 1 , further comprising an evaporation apparatus,
connected to the first particle suspension inlet line,
wherein the evaporation apparatus comprises:
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 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, wherein the third fluid conduit annularly surrounds a portion of the fluid contacting chamber, and
wherein the solvent removal chamber comprises:
a carrier gas entrance orifice;
a solvent removal gas exit orifice centrally connected to the top; and
a product exit orifice connected to the bottom of the solvent removal vessel.

5. The system of claim 4 , 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.

6. The system of claim 4 , 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.

7. The system of claim 4 , 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.

8. The system of claim 4 , wherein the first fluid conduit and the second fluid conduit are co-axial for a first portion of the first fluid conduit length.

9. The system of claim 4 , wherein the second fluid conduit annularly surrounds a first portion of the first fluid conduit.

10. The system of claim 4 , wherein a diameter of the fluid contacting chamber is larger than a diameter of the first fluid conduit.

11. The system of claim 4 , 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.

12. The system of claim 4 , 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.

13. The system of claim 4 , 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.

14. The system of claim 4 , wherein the atomizing nozzle is mounted to and extending through the top of the solvent removal vessel.

15. The system of claim 4 , further comprising a rinse nozzle mounted to and extending through the top of the solvent removal vessel.

16. The system of claim 4 , wherein the circular wall has a central axis and the solvent removal gas exit orifice further comprises a tube extending into the solvent removal vessel residing along the central axis.

17. The system of claim 4 , wherein the solvent removal gas exit orifice further comprises a tube extending into the solvent removal vessel, wherein the tube is fitted with a narrowing cone.

18. The system of claim 4 , wherein the solvent removal gas exit orifice further comprises a tube extending into the solvent removal vessel, wherein the tube is fitted with a narrowing cone and an annular ring.

19. The system of claim 4 , 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.

Assignees

• Pacira Pharmaceuticals Inc

Inventors

• Schutt Ernest George
• Mcguire Ronald Warren
• Walters Peter Andrew
• Los Kathleen D A

Classifications

• A61P23/02

  Local anaesthetics · CPC title

• A61P23/00

  Anaesthetics · CPC title

• A61K31/445

  Non condensed piperidines, e.g. piperocaine · CPC title

• A61K9/1271 Primary

  Non-conventional liposomes, e.g. PEGylated liposomes or liposomes coated or grafted with polymers (liposomes as conjugates {A61K47/6911}) · CPC title

• A61K9/127

  Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant · CPC title