Patent ID: 6855277

Claim:
A method for the continuous production of lipid vesicles by in-line mixing, said method comprising: (a) preparing a lipid phase and storing the lipid phase in a first storage means that is maintained at a set temperature; (b) preparing an aqueous phase and storing the aqueous phase in a second storage means that is maintained at a set temperature; (c) combining the lipid and aqueous phases by means of a mixing device having first and second metering systems, a pre-mixing system and a mixer, by: transferring the lipid phase from the first storage means to the first metering system by a first pressurized transfer means and transferring the aqueous phase from the second storage means to the second metering system by a second pressurized transfer means; transferring the lipid phase from the first metering system to a first inlet orifice in the pre-mixing system by a third pressurized transfer means and transferring the aqueous phase from the second metering system to a second inlet orifice in the pre-mixing system by a fourth pressurized transfer means; wherein the lipid phase and aqueous phases are transferred to the pre-mixing system with a high velocity creating turbulent flow; combining the lipid and aqueous phases in the pre-mixing system by shear mixing under conditions to insure that the lipid phase becomes fully hydrated by the aqueous phase to form a pre-mixed formulation; and transferring the pre-mixed formulation from an outlet orifice of the pre-mixing system to the mixer; (d) forming a mixed formulation containing lipid vesicles, in the mixer by causing the pre-mixed formulation to traverse the mixer; (e) optionally measuring the optical properties of the lipid vesicles; and (f) dispensing the mixed formulation from the mixer into a storage chamber, into a means for further modification of the properties of the lipid vesicles, or into a means of packaging the mixed formulation; wherein each metering system comprises a precise metering pump and a manifold, where each pump and manifold have a plurality of inlet and outlet means, 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.