Patent Application
20150343453
The invention relates generally to a media milling apparatus for the production of fine grade particulate substances. More specifically, the invention relates to the use of fluid energy as the energy source to effect milling of materials within a media mill apparatus.
Particle size reduction via wet and dry milling techniques represents an important manufacturing approach for many industrial applications, including pharmaceuticals, chemicals, paints, inks, minerals, agrochemicals, foods, rubber, energy, electronics, and biotechnology. In practice, it is accepted that finer particle size can be achieved with wet milling than by dry grinding techniques. Wet milling techniques such as ball milling or media milling can produce particles less than 1 micron, and in some cases particle sizes less than 100 nm can be achieved. In contrast, dry grinding techniques are generally limited to 10-20 micron particle sizes. Fluid energy jet milling of dry materials has been shown to be capable of achieving particle sizes in the 5-10 micron range.
Dry Milling Processes
Dry milling processes that utilize mechanical impact or shear of materials include jaw crushers, gyratory crushers, impact mills, roll crushers, and shredders. The energy supplied to effect material milling is generally accomplished through transfer of kinetic energy from a drive motor to machine elements that produce impact or shearing forces with materials to be milled. These devices do not incorporate the use of milling media.
Dry milling processes that utilize fluid energy to effect milling of materials include fluid-energy jet mills, such as centrifugal jet mills, opposing jet mills, and fluidized bed jet mills. A detailed description of jet mills is presented by Gossett [Chem. Process. (Chicago), 29(7), 29 (1966)]. In the centrifugal class of jet mills, the fluid energy is admitted in fine high-velocity streams at an angle around a portion or all of the periphery of a grinding and classifying chamber. An example is U.S. Pat. No. 6,789,756 to Beliaysky, herein incorporated by reference. In fluidized-bed jet mills, fluid streams, typically compressed air, convey the particles at high velocity into a chamber where two streams impact upon each other. Particle size reduction in jet mills is generally achieved by high velocity collisions between material particles entrained in high velocity gas stream within the jet mill chamber. By controlling the perturbations occurring within the air vortex, a significant influence on the pulverization process is achieved. Not all particles are completely milled, however, in one circuit. Jet mills often incorporate internal particle classification features to return un-milled particles to the milling chamber. Most of these mills utilize the energy of the flowing gas stream to effect centrifugal classification. Since jet mills generally have no drive motor, there is not the requirement for use of mechanical seals. Jet mills are considered high-energy milling systems, with fluid velocities greater than 10 m/sec. Jet mills do not incorporate the use of milling media to effect particle size reduction of materials and therefore have limited utility in production of material particle size reduction below 5 microns.
Dry milling processes that utilize milling media to effect milling of materials include ball or pebble mills, vibratory mills and attritors. In these mills, collisions of milling media result in shear and impact forces that result in dry material particle size reduction. In ball or pebble mills, the mechanical rotation of the ball mill milling chamber gives rise to gravitational cascading of the milling balls or pebbles that results in shear and impact forces that cause particle size reduction. Ball or pebble mills are generally considered low-energy input milling systems with media flow speeds less than 1 m/sec and are characterized by lengthy milling times, often on the order of several days. Similarly, vibratory mills utilize oscillating vibrations of the milling chamber to cause movement of the milling media to effect particle size reduction. Vibratory mills are generally considered low/medium energy input milling systems with media flow speeds in the range of 1-5 m/sec. Attritors (Union Process Inc.) are a class of stirred media mills that utilize mechanical agitation of milling media by means of a motor-driven mixer within the milling chamber. Attritors are generally considered medium-energy-input systems, with agitator speeds of less than 5 m/sec peripheral velocity.
Wet Milling Processes
Particle size reduction accomplished by wet milling processes includes application of impact and shearing forces delivered by equipment to effect comminution.
Examples of impact mills include high-speed impingement mills. Examples of shearing mills include colloid mills, three-roll mills and high-speed stone mills. These classes of mills do not utilize milling media to effect material particle size reduction and have limited utility in the production of material particle sizes below 5 microns.
Wet milling processes that incorporate the use of milling media include shot mills, ball and pebble mills, sand and bead mills and attritors. The comminution forces utilized in these media mills generally include a combination of impact and shearing forces. Wet media milling processes generally are capable of production of material particle sizes below 5 microns.
Wet milling processes that utilize milling media to effect milling of materials include ball or pebble mills, sand and bead mills, vibratory mills and attritors. Materials to be processes generally exist in a solid or semi-solid state dispersed within a liquid medium. Slurries or dispersions processed within such mills often utilize the addition of polymeric or surfactant stabilizers to promote particle dispersion and stabilization. In these mills, collisions of milling media result in shear and impact forces that result in material particle size reduction. In ball or pebble mills, the mechanical rotation of the ball mill milling chamber gives rise to gravitational cascading of the milling balls or pebbles within the mill that results in shear and impact forces that cause particle size reduction. Ball or pebble mills are generally considered low-energy input milling systems with media flow speeds less than 1 m/sec and are characterized by lengthy milling times, often on the order of several days. Similarly, vibratory mills utilize oscillating vibrations of the milling chamber to cause movement of the milling media to effect particle size reduction. Vibratory mills are generally considered low/medium energy input milling systems with media flow speeds in the range of 1-5 m/sec. Attritors (Union Process Inc.) are a class of stirred media mills that utilize mechanical agitation of milling media by means of a motor-driven mixer within the milling chamber. Attritors are generally considered medium-energy-input systems, with agitator speeds of less than 5 m/sec peripheral velocity. Such low, low-medium and medium energy input systems generally cannot utilize media smaller than 2 mm, since larger media are required to overcome the viscous resistance associated with flow in lower energy systems. As such, these systems generally have limited applicability to very fine milling of materials to particle sizes less about 1 micron.
High-energy wet media mills have in recent years become preferred and widely used for the production of very fine particulate materials less than 1 micron. Indeed, nanotechnology materials have been processed in size ranges below 100 nm using these mills. These media mills typically include a cylindrical vessel housing a vertically or horizontally mounted agitator shaft having shear members extending therefrom. Typically, a dispersion consisting of the product to be milled and a milling media is introduced into the vessel. Rotating the agitator causes the media to impact and shear the product into a finer grade. In traditional prior art mills an agitator shaft is connected through some means to a motor via either a mechanical or magnetic coupling. The agitator shaft is coupled at one point to a milling head and at another point to the motor. In order to prevent the milled product from leaking into the area wherein the drive shaft extends into the milling chamber, seals of some type, e.g., lip seals or mechanical seals, are used. Typically, lip seals have a short lifespan and have limited utility in commercial mills. Mechanical seals are broadly used in commercial mills, although there are numerous disadvantages. Such disadvantages include the requirement for a lubricant that can cause product contamination, difficulty in cleaning and sterilization due to complex designs, seal failure and associated process shutdowns and limitations in operating speeds and milling chamber pressures. Seal failure can occur due to heat generation, chemical attack, rotational shaft deflections, vibration, seal fluid vaporization or crystallization.
Wet high-energy media mills that utilize magnetic coupling of the agitator to a drive motor solve many of the problems associated with the use of mechanical seals. However, such magnetically-coupled mills generally are limited to small-scale equipment with limited speed capabilities due to the inherent limitations of magnetic coupling technology.
Further disadvantages of high-energy media mills include the use of complex agitation systems, drive systems and cooling systems which result in high fabrication costs. Due to milling chamber pressure limitations associated with mechanical seals, milling pressures must be maintained at relatively low levels to avoid seal failure. Such low pressures limit product flow rate through mill and ability to dissipate heat generated during milling. Also, mill speeds and related milling efficiencies are limited by mechanical drive systems such as bearings, mechanical seals, and milling chamber cooling efficiencies. Due to limitations of mill agitator speeds and limited media separator screen surface area, the use of smaller milling media is limited in such designs, such media being increasingly desirable for preparation of very fine particulate products
Provided in accordance with an exemplary embodiment of the present invention is fluid energy media mill for milling a substantially particulate solid material. The fluid energy media mill includes at least one hollow milling chamber 101 having a top 108, a bottom 111, and a side wall 114. Milling media is disposed in the hollow milling chamber 101. The milling chamber 101 has at least one inlet 102 along its side wall 114. The inlet 102 is configured to introduce the material into the hollow milling chamber 101 and promote a flow (vortex or turbulent) of the material and milling medium within the hollow milling chamber 101. The milling chamber 101 has an outlet 103 connected to the hollow milling chamber 101 to which a pump 104 is in fluid communication with the inlet 102 for introducing material through the hollow milling chamber 101.
The invention is best understood from the following detailed description when read in connection with the accompanying drawing. It is emphasized that, according to common practice, the various features of the drawing are not to scale. On the contrary, the dimensions of the various features are arbitrarily expanded or reduced for clarity. Included in the drawing are the following figures:
Referring now to
In an exemplary embodiment, milling chamber 101 is generally cylindrical in shape and has a volume of about 100, 50, 25, 10, 5, 1, 0.5 or 0.1 liters. The ratio of milling chamber height to diameter is in the range of about 100, 10, 5, 1, 0.2, 0.1, 0.01; consistent with the principle that a larger height/diameter ratio favors centrifugal separation of media for a given volume chamber.
On side wall 114 is at least one fluid inlet 102 having an inlet conduit 105 releaseably coupled thereto. Fluid inlet 102 is in fluid communication with milling chamber interior 204 as shown in more detail in
In the embodiments where discharge member 115 is a screen 112, screen 112 may be of any geometry sufficient to prevent the uptake of milling media 106 into outlet 103. Screen 112 may be constructed from a variety of materials. The screen is constructed with a screen opening size and overall surface area so that milling media 106 are not taken up through outlet 103 while the fluidized material is allowed to pass.
In an alternative embodiment, discharge collector 115 is a centrifugal separator such as a vortex finder. A vortex finder is commonly used in hydrocylones to promote centrifugal separation of solid particles from liquids (reference: Solid-Liquid Separations, L. Svarovsky, 4th edition, 2000, chapter 6: Hydrocyclones). A vortex finder facilitates separation of solids from a liquid slurry as is understood by one of ordinary skill in the art. The vortex finder as discharge collector 501 protrudes into milling chamber interior 204 to prevent immediate escape of the milling media introduced from inlet 102, and gives the milling media the opportunity to become entrained in vortex flow and be centrifuged to the chamber wall. In this configuration, the milling media once charged establishes vortex flow with the fluid material and the milling media is retained in the milling chamber due to centrifugal separation, but the fluid material is removed through the vortex finder 501 and outlet 103.
Outlet conduit 107 is releaseably coupled to the other end of outlet 103 Outlet conduit 107, according to the embodiment shown in
Shown in
Operation of fluid energy mill 100 includes introducing fluidized material into milling chamber 101 through inlet 102, mixing with milling media 106, disposed therein, so as to give rise to a vortex fluid flow (shown by the directional arrow generally referenced as 205 in
A high degree of comminution and a narrow range of the particle size of the material to be milled is achieved with sufficient vortex flow within milling chamber interior 204.
In exemplary embodiments, the fluid portion of the fluidized material is an aqueous fluid, such a water or sucrose solution or stabilizer solution. In other embodiments, the fluid is compressed gas or a non-aqueous fluid depending on the solubility of the material to be milled. Introduction of the material is exemplified with reference to
According to an embodiment, the mill is pre-charged with a fluidized material, such as a drug substance suspended in water or a stabilizer solution. The volume of fluidized material is a pre-determined volume depending on the amount of material to be milled, the volume of the milling chamber, the capacity of the pump, and volume of the associated piping. According to this embodiment, the milling media is pre-charged to the milling chamber that is in-line with the other components of the mil as shown in
The fluid force or momentum flux generated within the milling chamber contributes to the comminution forces required to effect milling of the material fluid during concomitant flow with milling media. The fluid force is a function of fluid flow rate and velocity. Fluid flow rates can range from 1 to 1000 liters/minute. Fluid velocities can range from 1 to 1000 meters/second. Various system parameters influence the fluid force generated within the milling chamber. These include the pump type and size, nozzle geometry, number of inlet nozzles, fluid viscosity, fluid density and other parameters commonly understood to impact fluid flow dynamics. Suitable pumps include positive displacement pumps, centrifugal pumps or other pumps capable of conveying fluids over a flow rate range of 1 to 1000 liters/minute with a pressure range over 1 to 10,000 psi.
In alternative embodiments, such as shown in
Also shown in
The amount of milling medium 106 present in the mill is predicated upon a variety of factors including the volume of the milling chamber, the material fluid flow rate, the material fluid velocity and physical characteristics of the fluid such as viscosity, density and feed size of material to be milled. In addition, the amount of milling media is also predicated on the milling media properties, including size, density, geometry and hardness. Typically, the milling media volumetric charge ranges from 1 to 99% of the working volume of the milling chamber, which includes the milling chamber volume less the volume of the discharge collector.
The following examples illustrate embodiments of the invention described herein.
The purpose of this example was to demonstrate the utility of the invention to effect particle size reduction in the preparation of a nanoparticulate dispersion of meloxicam using yttria-stabilized zirconia milling media.
5.555 kg of aqueous slurry of 5% meloxicam (AMSA S.P.A.), 1% Povidone K30 (Spectrum Chemical Mfg. Corp.) and 0.05% Docusate Sodium (Spectrum Chemical Mfg. Corp.) was charged to the reservoir of the system illustrated in
Samples were withdrawn for particle size analysis at time 0, 1, 2, 4, and 8 hours (Horiba LA950 particle size analyzer, Horiba Instruments, Irvine, Calif.). The results are shown in Table 1. In the table below, the value for D50 is the particle size below which 50% of the meloxicam particles fall. Similarly, D90 is the particle size below which 90% of the meloxicam particles fall. The results demonstrate rapid particle size reduction of the meloxicam particles.
The purpose of this example was to demonstrate the utility of invention to effect particle size reduction in the preparation of a nanoparticulate dispersion of meloxicam using glass media.
5.555 kg of aqueous slurry of 5% meloxicam (AMSA S.P.A.), 1% Povidone K30 (Spectrum Chemical Mfg. Corp.) and 0.05% Docusate Sodium (Spectrum Chemical Mfg. Corp.) was charged to the reservoir of the system illustrated in
Samples were withdrawn for particle size analysis at time 0, 1, 2, 4, and 8 hours (Horiba LA950 particle size analyzer, Horiba Instruments, Irvine, Calif.). The results are shown in Table 2. In the table below, the value for D50 is the particle size below which 50% of the meloxicam particles fall. Similarly, D90 is the particle size below which 90% of the meloxicam particles fall. The results demonstrate rapid particle size reduction of the meloxicam particles.
The purpose of this example was to demonstrate the utility of the invention to conduct milling without the use of a media separator screen.
7 kg of an aqueous 50% sucrose solution was charged to the reservoir of the system illustrated in
Once steady state recirculation flow was established, the milling media was fed over the course of 30 minutes from the media feed hopper, through the eductor, into the milling chamber. During the course of media feed to the milling chamber, system pressure decreased from 156 psi to 136 psi, system temperature increased from 17 C to 37 C, and system flow rate increased from 33 to 35 l/min.
Visual examination through a clear Plexiglas cover on the milling chamber indicated high speed vortex flow of the media and sucrose solution mixture, confirming the development of a high-energy milling condition.
After 15 minutes of recirculation, the process was stopped and the media safety screen was disassembled to measure the amount of media that escaped the mill. It was found that <1 cc of media escaped the mill during this example, indicating good media retention within the mill.
The purpose of this example was to demonstrate the utility of the invention to conduct milling without the use of a media separator screen.
This example was a replication of Example 3, but included the following variations:
The milling chamber comprised a cylindrical milling chamber with a 20 cm diameter, 5 cm height and a 1600 cc working volume. Four tangentially mounted inlets were attached to the milling chamber, each equipped with a 2.5 mm tapered nozzle. The inlets were mounted at a 12:00, 3:00, 6:00 and 9:00 positions, 2.5 cm from the milling chamber base.
During the course of media feed to the milling chamber, system pressure remained constant at approximately 150 psi, system temperature increased from 15 C to 35 C, and system flow rate increased from 35 to 36 l/min.
Visual examination through a clear Plexiglas cover on the milling chamber indicated high speed vortex flow of the media and sucrose solution mixture, confirming the development of a high-energy milling condition.
Following completion of media feed to the milling chamber, the process was stopped and the media safety screen was disassembled to measure the amount of media that escaped the mill. It was found that 150 cc of media escaped the mill during this example, indicating poor media retention within the mill.
The purpose of this example was to demonstrate the utility of the invention to conduct milling without the use of a media separator screen.
This example was a replication of Example 3, but included the following variations:
The milling chamber comprised a cylindrical milling chamber with a 10 cm diameter, 5 cm height and a 400 cc working volume. Two tangentially mounted inlets were attached to the milling chamber, each equipped with a 3.5 mm tapered nozzle, mounted at a 3:00 and 9:00 position, 2.5 cm from the milling chamber base.
200 cc of yttria-stabilized zirconia milling media (0.5 mm, Tosoh) was charged to the media feed hopper.
During the course of media feed to the milling chamber, system pressure decreased from 160 psi to 120 psi, system temperature increased from 21 C to 43 C, and system flow rate increased from 36 to 37 l/min.
Visual examination through a clear Plexiglas cover on the milling chamber indicated high speed vortex flow of the media and sucrose solution mixture, confirming the development of a high-energy milling condition.
Following completion of media feed to the milling chamber, the process was stopped and the media safety screen was disassembled to measure the amount of media that escaped the mill. It was found that <1 cc of media escaped the mill during this example, indicating good media retention within the mill.
The purpose of this example was to demonstrate the utility of the invention to conduct milling without the use of a media separator screen.
This example was replication of Example 3, but included the following variations:
400 cc of yttria-stabilized zirconia milling media (0.5 mm, Toshoh) was charged to the media feed hopper.
Four tangentially mounted inlets were attached to the milling chamber, each equipped with a 9 mm untapered nozzle. 2 inlets were mounted at a 3:00 and 9:00 position, 2.5 cm from the milling chamber base, and 2 inlets were mounted at a 6:00 and 12:00 position, 7.5 cm from the milling chamber base.
The sucrose solution was circulated from the reservoir by means of a centrifugal pump (Berkeley 1.5 hp, model S39522, 3450 rpm), into the milling chamber and returned to the reservoir in a closed-loop recirculation process.
During the course of media feed to the milling chamber, system pressure decreased from 44 psi to 23 psi, system temperature increased from 15 C to 44 C, and system flow rate increased from 69 to 117 l/min.
Visual examination through a clear Plexiglas cover on the milling chamber indicated high speed vortex flow of the media and sucrose solution mixture, confirming the development of a high-energy milling condition.
Following completion of media feed to the milling chamber, the process was stopped and the media safety screen was disassembled to measure the amount of media that escaped the mill. It was found that <1 cc of media escaped the mill during this example, indicating good media retention within the mill.
The purpose of this example was to demonstrate the utility of the invention to conduct milling without the use of a media separator screen.
This example was replication of Example 6, but included the following variations:
No vortex finder was attached to the milling chamber outlet.
During the course of media feed to the milling chamber, system pressure decreased from 35 psi to 6 psi, system temperature increased from 9 C to 31 C, and system flow rate increased from 50 to 86 l/min.
Visual examination through a clear Plexiglas cover on the milling chamber indicated high speed vortex flow of the media and sucrose solution mixture, confirming the development of a high-energy milling condition.
Following completion of media feed to the milling chamber, the process was stopped and the media safety screen was disassembled to measure the amount of media that escaped the mill. It was found that 200 cc of media escaped the mill during this example, indicating poor media retention within the mill.
The purpose of this example was to demonstrate the utility of the invention to conduct milling without the use of a media separator screen.
This example was replication of Example 5, but included the following variations:
125 cc of yttria-stabilized zirconia milling media (0.5 mm, Toshoh) was charged to the media feed hopper.
Two tangentially mounted inlets were attached to the milling chamber, each equipped with a 5.5 mm tapered nozzle, mounted at a 3:00 and 9:00 position, 2.5 cm from the milling chamber base.
The sucrose solution was circulated from the reservoir by means of a centrifugal pump (Berkeley 1.5 hp, model S39522, 3450 rpm), into the milling chamber and returned to the reservoir in a closed-loop recirculation process.
During the course of media feed to the milling chamber, system pressure decreased from 55 psi to 50 psi, system temperature increased from 10 C to 40 C, and system flow rate increased from 37 to 54 l/min.
Visual examination through a clear Plexiglas cover on the milling chamber indicated high speed vortex flow of the media and sucrose solution mixture, confirming the development of a high-energy milling condition.
Following completion of media feed to the milling chamber, the process was stopped and the media safety screen was disassembled to measure the amount of media that escaped the mill. It was found that <1 cc of media escaped the mill during this example, indicating good media retention within the mill.
The purpose of this example was to demonstrate the utility of the invention to conduct milling without the use of a media separator screen.
This example was replication of Example 4, but included the following variations:
300 cc of glass milling media (0.5-0.75 mm Type S Glass, Ceroglass Technologies Inc.) was charged to the media feed hopper.
Four tangentially mounted inlets were attached to the milling chamber, each equipped with a 5.5 mm tapered nozzle.
The sucrose solution was circulated from the reservoir by means of a centrifugal pump (Berkeley 1.5 hp, model S39522, 3450 rpm), into the milling chamber and returned to the reservoir in a closed-loop recirculation process.
During the course of media feed to the milling chamber, system pressure decreased from 44 psi to 34 psi, system temperature increased from 21 C to 44 C, and system flow rate increased from 65 to 69 l/min.
Visual examination through a clear Plexiglas cover on the milling chamber indicated high speed vortex flow of the media and sucrose solution mixture, confirming the development of a high-energy milling condition.
Following completion of media feed to the milling chamber, the process was stopped and the media safety screen was disassembled to measure the amount of media that escaped the mill. It was found that 125 cc of media escaped the mill during this example, indicating poor media retention within the mill.
The purpose of this example was to demonstrate the utility of the invention to conduct milling without the use of a media separator screen.
This example was replication of Example 9, but included the following variations:
Water was used in place of 50% sucrose solution
During the course of media feed to the milling chamber, system pressure decreased from 39 psi to 33 psi, system temperature increased from 11 C to 27 C, and system flow rate increased from 55 to 69 l/min.
Visual examination through a clear Plexiglas cover on the milling chamber indicated high speed vortex flow of the media and sucrose solution mixture, confirming the development of a high-energy milling condition.
Following completion of media feed to the milling chamber, the process was stopped and the media safety screen was disassembled to measure the amount of media that escaped the mill. It was found that <1 cc of media escaped the mill during this example, indicating good media retention within the mill.
| Number | Date | Country | |
|---|---|---|---|
| 62004124 | May 2014 | US |
