PRODUCTION OF MULTIVESICULAR LIPOSOMES

• US 20070235889A1
• Filed: 02/25/2007
• Published: 10/11/2007
• Est. Priority Date: 11/14/1997
• Status: Active Grant

• Current Assignee: Pacira Pharmaceuticals, Inc. (Pacira Biosciences, Inc.)
• Original Assignee: SkyePharma PLC. (Vectura Group Ltd.)
• Inventors: Meissner, Dagmar, Pepper, Clint, HARTOUNIAN, Hartoun
• Granted Patent: US 9,585,838 B2
• Time in Patent Office: Days
• US Class Current: 264/4.100
• CPC Class Codes: A61K 31/439 the ring forming part of a bridged ring system, e.g. quinuclidine 8-azabicyclo [3.2.1] octanes A61K31/46
• CPC Class Codes: A61K 31/7036 having at least one amino group directly attached to the carbocyclic ring, e.g. streptomycin, gentamycin, amikacin, validamycin, fortimicins
• CPC Class Codes: A61K 31/7068 having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
• CPC Class Codes: A61K 38/30 Insulin-like growth factors, i.e. somatomedins, e.g. IGF-1, IGF-2 insulin-like growth factor binding protein A61K38/1754
• CPC Class Codes: A61K 9/127 Liposomes
• CPC Class Codes: A61K 9/1277 Processes for preparing; Proliposomes
• CPC Class Codes: A61P 23/00 Anaesthetics
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: B65G 2814/0397 for ships
• CPC Class Codes: B65G 67/00 Loading or unloading vehicles by means incorporated in the vehicles B60-B64, e.g., B60P1/00, B61D9/00, B63B27/00, B64D9/00; ground or aircraft-carrier-deck installations for aircraft B64F1/32

Abstract

Multivesicular liposomes are prepared at commercial scales by combining a first w/o emulsion with a second aqueous solution to form a w/o/w emulsion using a static mixer. Solvent is removed from the resulting emulsion to form multivesicular liposome-containing compositions. Further optional process steps include primary filtration and secondary cross-flow filtration. The products produced according to the processes of the invention can be produced through a series of aseptic steps.

Claims

1. A process for preparing a multivesicular liposomal particle composition of pre-determined, uniform size distribution, the process comprising:

a) providing a first emulsion by mixing a first aqueous phase and a volatile water-immiscible solvent phase, said solvent phase comprising at least one amphipathic lipid and at least one neutral lipid;

b) mixing and emulsifying said first emulsion and a second aqueous phase to provide a second emulsion, said second emulsion comprising a continuous aqueous phase;

c) sparging the volatile water-immiscible solvent from the second emulsion to form a composition of multivesicular liposomal particles, wherein the sparging comprises at least two steps having different gas flow rates; and

d) filtering the multivesicular liposomal particle composition by cross-flow filtration.

2-51. -51. (canceled)