Method and apparatus for liposome production

An apparatus for the continuous production of lipid vesicles by in-line mixing, said apparatus comprising:

• (a) a lipid phase storage means capable of being maintained at a set temperature and a first pressurized transfer means for transferring the lipid phase from the storage means;
• (b) an aqueous phase storage means capable of being maintained at a set temperature and a second pressurized transfer means for transferring the aqueous phase from the storage means;
• (c) a mixing device comprising:
• a first metering system for receiving the lipid phase from the first pressurized transfer means;
• a second metering system for receiving the aqueous phase from the second pressurized transfer means;
• a pre-mixing system for preparing a pre-mixed formulation;
• a third pressurized transfer means for transferring the lipid phase from the first metering system to a first inlet orifice on the pre-mixing system and a fourth pressurized transfer means for transferring the aqueous phase from the second metering system to a second inlet orifice on the pre-mixing system;
• a mixer for preparing a mixed formulation comprising lipid vesicles, having a mixing chamber and an optional means for determining the optical properties of the mixed formulation;
• a means for transferring the pre-mixed formulation from the outlet orifice of the pre-mixing system to the mixing chamber;
• and an optional means for applying ultrasonic energy to the pre-mixing system, the mixing chamber or both, wherein each metering system comprises a precise metering pump and a manifold, wherein each pump and manifold have a plurality of inlet and outlet means, where each pump inlet means communicates with a manifold outlet means and each pump outlet means communicates with a manifold inlet means;
• where each pump inlet means is 90° out of phase with the preceding pump inlet means and the successive pump inlet means, and the manifold further comprises a manifold outlet orifice and a manifold inlet orifice;
• and
• (d) a dispensing means for transferring the mixed formulation from the mixing chamber into a storage chamber.