Drug – bio-affecting and body treating compositions – Effervescent or pressurized fluid containing – Organic pressurized fluid
Reexamination Certificate
1999-11-22
2001-12-18
Acquah, Samuel A. (Department: 1711)
Drug, bio-affecting and body treating compositions
Effervescent or pressurized fluid containing
Organic pressurized fluid
C521S050000, C424S043000, C424S045000, C424S489000, C239S099000, C239S101000
Reexamination Certificate
active
06331290
ABSTRACT:
The present invention relates to a method and an apparatus for making particles from a liquid feedstock, the particles either being solid or being liquid droplets in an aerosol, and being substantially monodisperse.
Producing particles which are of diameter less than say 5 &mgr;m is of particular importance for pharmaceutical applications, as powders comprising such small particles provide advantages. For example they dissolve more easily because of their large surface area; such small particles allow flexibility in the packaging of drugs and provide greater freedom in selecting the mode of delivery; small particles allow more precise dosing, enabling the exact quantity of an active ingredient to be achieved; and for efficient drug delivery via the respiratory tract it is desirable to use an aerosol of particles with a limited size range to ensure particles are inhaled and reach the desired part of the the body. Known methods for producing such small particles include milling, and spray-drying. Milling involves mixing an active drug with appropriate excipients, and grinding the mixture in a suitable mill; however it is difficult to produce monodisperse particles, and furthermore the milling generates heat which may alter the structure of the active ingredient. Spray drying requires a liquid feedstock to be sprayed into a tank of hot gas so the solvent evaporates, leaving dry particles which can be collected. It is again difficult to obtain monodisperse particles, because the spray is polydisperse. A monodisperse particle fraction can in each case be obtained by sieving, although this decreases the yield.
According to the present invention there is provided a method for making particles from a liquid feedstock comprising a pharmaceutical composition and a solvent, the method comprising supplying the feedstock to an electronic droplet generator, the generator comprising a feed chamber to which the feedstock is supplied, a dispensing chamber having an inlet port communicating with the feed chamber and having an outlet port, and electronic means for applying a pressure pulse to the feed chamber and a pressure pulse to the dispensing chamber so that substantially all the liquid feedstock in the dispensing chamber is ejected at once, to form a droplet of the liquid feedstock, the electronic means applying the pressure pulses repeatedly, and the resulting droplets forming an aerosol in a holding chamber adjacent to the outlet port either until the solvent has evaporated, or until the droplets have been inhaled by a patient.
The pressure pulses may be provided by piezoelectric means, as in the jet printing device of WO 97/48557. The pressure pulses provided to the feed chamber and to the dispensing chamber may be simultaneous. The size of the droplets is determined primarily by the volume of the dispensing chamber, and may be 20 &mgr;m or less, for example 10 &mgr;m or 5 &mgr;m. If particles of dry powder are to be made, then when the solvent has had time to evaporate the resulting particles are trapped, for example using a cyclone. The dry particles will be smaller than the droplets, their size depending on the proportion of the liquid feedstock which evaporates, but they too will be substantially monodisperse.
In one example the liquid feedstock is generated by mixing two liquid streams immediately prior to supplying the feedstock to the generator; the mixing may be performed using a fluidic vortex mixer. A fluidic vortex mixer comprises a substantially cylindrical chamber with an axial outlet duct at the center of an end wall of the chamber, and with at least one substantially tangential inlet near the periphery of the chamber to create a spiralling flow in the chamber. A second liquid may be supplied through a second tangential inlet or through a radial inlet. Such a mixer achieves very intimate mixing of the two liquids in a short time, but does not subject the liquids to high shear.
The invention also provides an apparatus for generating particles, the apparatus comprising means to supply a liquid feedstock comprising a pharmaceutical composition and a solvent to an electronic droplet generator, the generator comprising a feed chamber to which the feedstock is supplied, a dispensing chamber having an inlet port communicating with the feed chamber and having an outlet port, and electronic means for applying a pressure pulse to the feed chamber and a pressure pulse to the dispensing chamber so that substantially all the liquid feedstock in the dispensing chamber is ejected at once, to form a droplet of the liquid feedstock, the electronic means being arranged to apply the pressure pulses repeatedly, and a holding chamber adjacent to the outlet port in which the droplets remain as an aerosol either until the solvent has evaporated, or until the droplets have been inhaled by a patient.
The apparatus may comprise a plurality of such electronic droplet generators to which the same feedstock is supplied, the droplets from the generators passing into a common holding chamber.
REFERENCES:
patent: 3775058 (1973-11-01), Bush
patent: 4746466 (1988-05-01), Takahashi
patent: 5836515 (1998-11-01), Fonzes
patent: 2831970 (1980-02-01), None
patent: 3516144 (1986-11-01), None
patent: 0532349 (1993-03-01), None
patent: 0656230 (1995-06-01), None
patent: 92/11050 (1992-07-01), None
patent: WO 94/20204 (1994-09-01), None
patent: WO 97/48557 (1997-12-01), None
patent: 98/26827 (1998-06-01), None
Accentus PLC
Acquah Samuel A.
Holt William H.
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