Stabilized capillary microjet and devices and methods for producing same

• US 6,405,936 B1
• Filed: 11/02/2001
• Issued: 06/18/2002
• Est. Priority Date: 05/13/1996
• Status: Expired due to Fees

• Current Assignee: Universidad de Sevilla
• Original Assignee: Universidad de Sevilla
• Inventors: Ganan-Calvo, Alfonso
• Primary Examiner(s): Ganey, Steven J.
• Application Number:
  US10/053,472
• Time in Patent Office: 228 Days
• Field of Search: 239/3, 239/8, 239/290, 239/291, 239/371, 239/400, 239/419, 239/419.3, 239/422, 239/423, 239/424, 239/428, 239/338, 239/346, 239/434.5, 424/45, 128/200.21, 128/205.11, 128/204.16, 128/911, 261/76, 261/78.1, 261/78.2, 261/115, 261/116, 264/4, 264/4.1, 264/4.3, 264/4.6
• US Class Current: 239/8
• CPC Class Codes: A61M 15/0065 Inhalators with dosage or measuring devices A61M15/0028 takes precedence; dosage devices incorporated in aerosol cans B65D83/52
• CPC Class Codes: A61M 15/025 Bubble jet droplet ejection devices
• CPC Class Codes: A61M 2202/064 Powder
• CPC Class Codes: B01F 23/232 using flow-mixing means for introducing the gases, e.g. baffles
• CPC Class Codes: B01F 25/30 Injector mixers mixing by creating vortex flow B01F25/10
• CPC Class Codes: B01F 33/3011 using a sheathing stream of a fluid surrounding a central stream of a different fluid, e.g. for reducing the cross-section of the central stream or to produce droplets from the central stream
• CPC Class Codes: B01J 2219/00378 Piezoelectric or ink jet dispensers
• CPC Class Codes: B05B 1/02 designed to produce a jet, spray, or other discharge of particular shape or nature, e.g. in single drops, or having an outlet of particular shapeB05B1/26, B05B1/28, B05B1/34 take precedence
• CPC Class Codes: B05B 7/0475 with means for deflecting the peripheral gas flow towards the central liquid flow B05B7/0458 takes precedence
• CPC Class Codes: B05B 7/061 with several liquid outlets discharging one or several liquids
• CPC Class Codes: B05B 7/065 an inner gas outlet being surrounded by an annular adjacent liquid outlet
• CPC Class Codes: B05B 7/066 with an inner liquid outlet surrounded by at least one annular gas outlet
• CPC Class Codes: B05B 7/0884 the outlet orifices for jets constituted by a liquid or a mixture containing a liquid being aligned
• CPC Class Codes: B82Y 30/00 Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: C40B 60/14 for creating libraries
• CPC Class Codes: F02M 43/04 Injectors peculiar thereto
• CPC Class Codes: F02M 67/10 Injectors peculiar thereto, e.g. valve less type
• CPC Class Codes: F02M 69/047 injectors with air chambers, e.g. communicating with atmosphere for aerating the nozzles F02M69/325 takes precedence
• CPC Class Codes: F02M 69/08 characterised by the fuel being carried by compressed air into main stream of combustion-air
• CPC Class Codes: F23D 11/106 medium and fuel meeting at the burner outlet
• CPC Class Codes: G01N 15/1409 : Handling samples, e.g. injecting samples
• CPC Class Codes: G01N 2015/1406 : Control of droplet point
• CPC Class Codes: G01N 21/01 : Arrangements or apparatus for facilitating the optical investigation
• CPC Class Codes: Y10S 977/773 : Nanoparticle, i.e. structure having three dimensions of 100 nm or less
• CPC Class Codes: Y10S 977/888 : Shaping or removal of materials, e.g. etching
• CPC Class Codes: Y10S 977/89 : Deposition of materials, e.g. coating, cvd, or ald
• CPC Class Codes: Y10S 977/896 : Chemical synthesis, e.g. chemical bonding or breaking

Abstract

The invention is directed to a stable capillary microjet and a monodisperse aerosol formed when the microjet dissociates. A variety of devices and methods are disclosed which allow for the formation of a stream of a first fluid (e.g. a liquid) characterized by forming a stable capillary microjet over a portion of the stream wherein the microjet portion of the stream is formed by a second fluid (e.g. a gas). The second fluid is preferably in a different state from the first fluid—liquid-gas or gas-liquid combinations. However, the first and second fluids may be two different fluids in miscible in each other. The stable capillary microjet comprises a diameter d_j at a given point A in the stream characterized by the formula: $d_j\cong {\left(\frac{8{\rho }_1}{{\pi }^2\Delta P_g}\right)}^{1/4}Q^{1/2}$

wherein d_j is the diameter of the stable microjet, ≈ indicates approximately equally to where an acceptable margin of error is ±10%, ρ₁ is the density of the liquid and ΔP_g is change in gas pressure of gas surrounding the stream at the point A.

Claims

1. A method of manufacturing coated particles, comprising the steps of:

(a) forcing a liquid formulation comprising a pharmaceutically active drug through a channel of a first feeding source in a manner which causes a stream of the liquid drug to be expelled from a first exit opening at a first velocity;

(b) forcing a liquid comprising a coating material through a second channel concentrically positioned around the first channel in a manner which causes a stream of the liquid coating material to be expelled from a second exit opening at a velocity which is substantially the same as the first velocity whereby the stream of coating material is concentrically positioned around the stream of liquid drug;

(c) forcing a gas through a pressure chamber in a manner which causes the gas to exit the pressure chamber from an exit orifice positioned downstream of the concentrically positioned streams of liquid drug and coating material;

wherein the density of the liquid formulation comprising the pharmaceutically active drug is substantially the same as the density of the liquid comprising the coating material, and the gas focuses the concentrically positioned streams to a stable unified jet which flows out of the chamber exit orifice and breaks up into a first group of coated particles of the pharmaceutically active drug coated with the coating material; and

(d) repeating the steps (a)-(c) in a manner such that the coating on a second group of coated particles has a different thickness from the coating of the first group of coated particles.

2. The method of claim 1, wherein the repeating (d) of steps (a)-(c) is carried out in a separate manufacturing event.

3. The method of claim 1, wherein the repeating step (d) is carried out a plurality of times to obtain a plurality of groups of coated particles.

4. The method of claim 3, wherein each of the groups of coated particles has different coating thickness and combined groups of coated particles provide controlled release of the pharmaceutically active drug.

5. The method of claim 1, wherein the stable unified jet formed in each step (c) is comprises a diameter d_j at a given point A in the stream characterized by the formula:

$d_j\cong <br><br>{\left(\frac{8<br><br>{\mathrm{\rho <br><br>}}_1}{{\mathrm{\pi <br><br>}}^2<br><br>\mathrm{\Delta <br><br>}<br><br>\text{\hspace{1em}<br><br>}<br><br>P_g}\right)}^{1/4}<br><br>Q^{1/2}$

wherein d_j is the diameter of the stable unified jet, ≅

indicates approximately equally to where an acceptable margin of error is ±

10%, ρ

₁ is the average density of the liquid of the unified jet and Δ

P_g is change in gas pressure of gas surrounding the stream at the point A and Q is the total flow rate of the stable unified jet.

6. The method of claim 5, wherein d_j is a diameter in a range of about 1 micron to about 1 mm.

7. The method of claim 5, wherein the stable unified jet formed in each step (c) has a length in a range of from about 1 micron to about 50 mm.

8. The method of claim 5, wherein the stable unified jet formed in each step (c) is maintained, at least in part, by tangential viscous stresses exerted by the gas on a surface of the jet in an axial direction of the jet.

9. The method of claim 5, wherein the stable unified jet formed in each step (c) is further characterized by a slightly parabolic axial velocity profile.

10. The method of claim 5, wherein each group of particles of the pharmaceutically active drug coated with the coating material are characterized by having the same diameter with a deviation in diameter from one particle to another in a range of from about ±

3% to about ±

30%.

11. The method of claim 10, wherein the deviation in diameter from one particle to another in each group of particles is in a range of from about ±

3% to ±

10%.

12. The method of claim 1, wherein a given coated particle in each group of particles has a diameter in a range of about 0.1 micron to about 100 microns and other particles in that group have the same diameter as the given particle with a deviation of about ±

3% to about ±

30%.

13. The method of claim 1, wherein Δ

P=P₀−

P₁, the difference in pressure through the pressure chamber exit orifice, is equal to or less than twenty times the surface tension of the liquid comprising the coating material with the gas, divided by the radius of the stable unified jet.