Freeze drying apparatus and related method of freeze drying

Abstract

A freeze drying apparatus includes one or more processing columns, each column having a prilling section enabled to produce liquid droplets of a product caused to drop due to gravity, a vertical freezing chamber disposed beneath the prilling section having one or more nozzles that produces a cryogenic mist through which the liquid droplets fall and produces a plurality of frozen beads. A drying chamber disposed beneath the freezing chamber includes a heat generator for drying the frozen beads, wherein heat energy can be provided, for example, using conduction / convection, infrared (IR), microwave (RE) energy or combinations thereof. A condensing chamber is configured to draw sublimated water vapor from the frozen beads under vacuum. In an embodiment, the apparatus can include two or more processing columns, each processing column including a prilling section, freezing chamber and drying chamber disposed about a central condensing chamber and one or more collection vessels.

Description

FREEZE DRYING APPARATUS AND RELATED METHOD OF FREEZE DRYINGCross Reference to Related Application

[0001] This application claims priority to USSN 63 / 669,003, entitled: FREEZE DRYING APPARATUS AND RELATED METHOD OF FREEZE DRYING, filed July 9, 2024, the entire contents of which are incorporated by reference in its entirety.Technical Field

[0002] This application is directed generally to the field of freeze drying (lyophilization), and more specifically to an apparatus for freeze-drying a liquid material, such as for example, pharmaceuticals. According to at least one described embodiment, the apparatus generates droplets of the liquid material, which fall vertically within one or more processing columns, and then freezes the material in the form of a plurality of small beads. The heat energy required for sublimation of the frozen beaded material is then supplied under vacuum. The freeze dried material is then caused to be driven from the apparatus to a collection receptacle(s).Technical Background

[0003] Freeze drying or lyophilization is a process that removes a solvent or suspension medium, typically water, from a product. While the present disclosure uses water as an exemplary solvent, it will be understood that other solvents, such as, but not limited to alcohol, may also be removed in freeze drying processes.

[0004] In known freeze drying processes for removing water from a product material, the water in the product is frozen to form ice and, under vacuum, the ice is sublimed and the resulting water vapor flows to a condenser. The water vapor is condensed as ice and later is removed from the condenser. Freeze-drying is particularly useful in the pharmaceutical industry as the integrity of the product is preserved during the freeze drying process and product stability can be maintained and guaranteed over relatively long periods of time. The freeze dried product is, ordinarily, but not necessarily a biological substance.

[0005] Pharmaceutical freeze drying is often an aseptic process that requires sterile conditions within the freeze drying chamber(s). For these bulk products, it is crucial to insure that all components of the freeze drying system that come into contact with the product are sterile.

[0006] Most freeze drying in aseptic conditions is done in a single apparatus, namely a freeze dryer either designed to receive a plurality of vials, or bulk product contained in open trays, or trays with a vent. In one example of a batch freeze drying system 100, shown in FIG. 1, a batch of product 102 in a plurality of trays 104 is placed on one of a plurality of vertically arranged shelves 108. Alternately, the product 102 may be placed into vials 107, which are either manually or automatically loaded onto the shelves 108. The plurality of shelves 108 are vertically arranged within the freeze drying chamber 106. The shelves 108 support the trays 104, or vials 107, and are also configured to transfer suitable amounts of heat to and from the trays 104 and product 102 in the bulk configuration and to and from the vials 107 and the shelves 108 in the vial configuration, as required by the process. A heat transfer fluid, such as silicone oil, flows through a series of conduits that are formed within the shelves 108, which are used to remove or add heat.

[0007] Under vacuum, the frozen product 102 is heated sufficiently to cause sublimation of the ice within the product 102. Water vapor resulting from the sublimation of the ice flows through a passageway 110 into a condensing chamber 112 containing a number of condensing coils 114 or other surfaces 114 that are maintained below the condensation temperature of the water vapor. A coolant is passed through the condensing coils 114 to remove heat, causing the water vapor to condense as ice on the coils 114.

[0008] Both the freeze drying chamber 106 and the condensing chamber 112 are maintained under vacuum by the condensing action of the condenser along with using a vacuum pump 116, the latter being connected to the exhaust of the condensing chamber 112. Noncondensable gases contained in each of the chambers 106, 112 are removed by the vacuum pump 116 and exhausted via a higher pressure outlet 118.

[0009] Conventional freeze dryers are designed for aseptic vial drying and are not optimized to handle bulk product. The product must first be manually loaded in to the trays, freeze dried, and then manually removed from the trays. Moreover, handling of the trays is difficult, and creates the added risk of liquid spill. Heat transfer resistances between the product and the trays, and also between the trays and the shelves, may result in irregular heat transfer. Dried product must be removed from the trays after processing, resulting in product handling losses. All of these process must often be done while maintaining a sterile product.

[0010] Because the foregoing bulk process is performed on a large mass of product, the frozen material forms into a “cake,” which requires additional processes such as milling is required in order to achieve a suitable resulting powder and a uniform particle size. Cycle times may be longer than necessary due to the resistance of the formed large mass of product to heating and the poor irregular heat transfer characteristics between the plurality of trays, the product and the shelves.

[0011] Spray freeze drying has been suggested, in which a liquid substance is sprayed into a low temperature, low pressure environment, and water from the resulting frozen particles is sublimated by exposing the falling particles to radiant heat, as described, for example, in U.S. Patent No. 3,300,868. This process is limited to materials from which water vapor may be removed rapidly, while the particles are airborne, and requires the use of radiant heaters in a low temperature environment, reducing overall efficiency.

[0012] Spray freezing of a product by atomizing the product together with liquid nitrogen (LN2) or other cryogenic material such as a cold gas, has been suggested in conjunction with atmospheric freeze drying using a desiccating gas, such as nitrogen. An example of this process is described in U.S. Patent No. 7,363,726. Frozen particles are collected in a drying vessel having a bottom with a porous metal filter plate. The desiccating gas is passed through the product, creating a partial pressure of water vapor from the product over the dry desiccating gas, causing sublimation and / or evaporation of the water contained in the product. Such a process is not well suited for aseptic processing, because both the cold gas (LN2) and the desiccating gas must be sterile. The process may also consume large amounts of nitrogen. Atmospheric drying is typically slower than vacuum drying of equivalent amounts of powder.

[0013] The use of atomizing product nozzles in a spray freezing tower, as described in the above referenced ‘726 patent and also U.S. Patent No. 9,052,138, are inefficient as a considerable amount of frozen product tends to collect on the interior surfaces of the freezing tower. One technique, described in U.S. Patent No. 11,148,463 B2 produces a stream of liquid droplets in the freezing tower in which a coolant fluid is circulated within a cavity formed within the sidewalls of the tower in relation to a product dispensed within the tower and in indirect contact therewith.

[0014] Moreover, it is a prevailing goal in the field of lyophilization to increase throughput through the development and design of an effective continuous or semi-continuous freeze-dryingsystem in lieu of conventional batch systems, such as those systems shown and described according to FIG. 1. One method of creating frozen beads, via the prilling of a liquid product to generate liquid droplets, and contacting the product with a liquid cryogen, such as, for example, liquid nitrogen (LN2), is described in Applicant’s copending U.S. Patent Application Serial No. 63 / 447,388, entitled: DIRECT CONTACT SPRAY FREEZING SYSTEM, the entire contents of which are herein incorporated by reference. A prilling station produces the droplets of liquid material that are caused to be vibrated and dropped sequentially under the force of gravity through a cryogenic mist formed in a freezing tower disposed directly below the prilling station. The falling droplets are caused to freeze, wherein the size of the liquid droplets is considerably larger than that of the cryogen particles in the formed mist. Accordingly, freezing can occur without significant deflection of the falling liquid droplets as the droplets are frozen. In the afore described application, the frozen beads can be extracted via an airlock through an intermediate chamber as ported or transferred directly to a drying chamber (not shown).Brief Description

[0015] Therefore and according to at least one version, there is provided a freeze drying apparatus, the apparatus comprising at least one processing column comprising a prilling section disposed in an upper portion of the processing column enabled to produce liquid droplets of a product that are caused to drop under the force of gravity, a freezing chamber disposed beneath the prilling section including one or more nozzles that produces a cryogenic mist through which the liquid droplets fall and produces a plurality of frozen beads. A drying chamber disposed beneath the freezing chamber includes at least one heating source that is configured to provide sufficient energy within the drying chamber to sublimate the frozen beads under the application of vacuum. A condensing chamber is disposed in relation to the drying chamber of the processing column and configured to draw sublimated water vapor from the frozen beads under vacuum.

[0016] In at least one embodiment, an isolation valve is disposed between the prilling section and the freezing chamber. The isolation valve according to at least one version is hingably movable between an engaged position and an open position relative to the flow path of the generated liquid droplets. In at least one version, the isolation valve includes a sealing gasket that is also movable between the engaged and open positions.

[0017] According to at least one embodiment, the drying chamber can optionally include a stirrer mechanism. In one or more embodiments, the stirrer mechanism includes a stirrer device disposed at a floor of the drying chamber, as well as a drive mechanism. According to at least one version, the stirrer device can include one or more paddles that are configured to assist in drying and further to assist in moving the freeze dried material to the collection chamber.

[0018] In at least one version, the drying chamber can utilize an RF energy source. According to embodiments, a plate can be disposed between the freezing chamber of the apparatus and the drying chamber, the plate being defined by a mesh of spaced openings that are sized and shaped to permit the passage of the frozen beads. In at least one version, means are suitably configured to provide microwave (RF) energy to the confines of the drying chamber, that can be driven to create a uniform RF field within the drying chamber. In accordance with an alternative embodiment, the drying chamber can be configured to define a jacket or enclosure surrounding the drying chamber through which a heating fluid can be circulated. In accordance with yet another embodiment, a source of infrared radiation (IR) can alternatively be disposed for purposes of sublimating the collected frozen beads. In at least one embodiment, the source of infrared radiation can be used alone or in combination with the fluid-circulating chamber jacket.

[0019] According to at least another aspect of the present invention, there is provided a freeze-drying apparatus comprising comprising a condensing chamber and one or more processing columns disposed in relation to the condensing chamber. Each processing column(s) comprises a prilling section disposed in an upper portion of the processing column, the prilling section enabled to produce liquid droplets of a product that are caused to drop under the force of gravity, a freezing chamber disposed beneath the prilling section including one or more nozzles that produces a cryogenic mist in the freezing chamber through which the liquid droplets fall and produces a plurality of frozen beads; a drying chamber disposed beneath the freezing chamber in a lower portion of the processing column, the drying chamber including means for generating heat energy within the drying chamber, and drying the frozen beads and in which the condensing chamber is coupled to each of the one or more processing column(s) and configured to draw sublimated water vapor from the frozen beads formed in each of the processing columns.

[0020] According to at least one embodiment, the RF radiation in the form of microwaves used to heat a product as the advantage of performing what is known as “volumetric heating.”Volumetric heating exposes all the product disposed in the drying chamber to a uniform amount of heating energy, as compared with utilizing a heated surface that heats the product (e.g., beads) in contact with the heated surface. By utilizing the correct microwave frequency, and techniques to effectively scatter the microwave energy, a uniform microwave field can be produced in order to perform uniform volumetric heating.

[0021] Another advantage realized by the herein described processing apparatus is that of effective and uniform drying of product in the form of frozen beads without product agglomeration and static electricity buildup, as found in prior art processing apparatus. By drying the beads in place, the problems with maintaining beads in a frozen state while transporting them is avoided.

[0022] Yet another advantage is that one or more versions of the herein described apparatus are scalable, enabling various throughputs and providing a semi-continuous freeze drying system.

[0023] In addition, the herein described processing apparatus is fully capable of annealing the frozen product.

[0024] Still further, the herein described processing column(s) is capable of aseptic processing (CLP) and sterilization (SIP).

[0025] These and other technical features and advantages will be readily apparent from the following Detailed Description, which should be read in conjunction with the accompanying figures.Brief Description of the Drawings

[0026] FIG. l is a representation of a traditional bulk freeze drying system;

[0027] FIG. 2 is a schematic view of a direct contact spray freezing system used in accordance with aspects of the present invention;

[0028] FIG. 3 is the schematic view of the direct contact spray freezing system of FIG. 2, illustrating a conditioning process for the freezing tower prior to dispense of liquid product;

[0029] FIG. 4(A) is a partial top sectioned view of a portion of the direct contact spray freezing system of FIGS. 2 and 3;

[0030] FIG. 4(B) is a partial side sectional view of a droplet generator of the direct contact spray freezing systems of FIGS. 2, 3 and 4(A);

[0031] FIG. 5 is the schematic view of direct contact spray freezing system of FIGS. 2 - 4(B), illustrating the freezing of liquid droplets in accordance with aspects of the present invention;

[0032] FIG. 6 is a side view of a freeze drying apparatus in accordance with aspects of the present invention;

[0033] FIG. 7 is a side sectioned view of the freeze drying apparatus of FIG. 6;

[0034] FIG. 8 is an enlarged view of a portion of the freeze drying apparatus of FIGS. 6 and 7;

[0035] FIG. 9 is another enlarged view of an upper portion of the freeze drying apparatus of FIGS. 6-8;

[0036] FIG. 10 is a sectioned elevational view of a lower portion of the freeze drying apparatus in accordance with an embodiment;

[0037] FIG. 11 is another sectioned elevational view of the lower portion of the freeze drying apparatus of FIG. 10;

[0038] FIG. 12 is another sectioned elevational view of the lower portion of the freeze drying apparatus of FIGS. 10 and 11;

[0039] FIG. 13 is a sectioned elevational view of a drying chamber in accordance with another embodiment;

[0040] FIG. 14 is a sectioned elevational view of a drying chamber in accordance with yet another embodiment;

[0041] FIG. 15 is a top perspective view of a freeze drying apparatus in accordance with another exemplary embodiment; and

[0042] FIG. 16 is a bottom perspective view of the freeze-drying apparatus of FIG. 13.Detailed Description

[0043] The following describes a number of exemplary embodiments of a freeze drying apparatus and related methods that are made in accordance with aspects of the present invention.Throughout the following discussion, several terms are used in order to provide a suitable frame of reference for the accompanying drawings. These terms, which may include “inner,” “outer,” “above,” “below,” “first,” “second,” “section,” “portion,” “chamber,” “interior,” “exterior,” and the like, are not intended to overly limit the scope of the present invention, except where so specifically indicated.

[0044] In addition, the accompanying drawings are intended to depict salient features of the present invention. Accordingly, the drawings should not be relied upon for scalar purposes.

[0045] The processes and apparatus may advantageously be used in freezing and drying pharmaceutical products that require aseptic or sterile processing, such as injectables. The methods and processes may also be used, however, in processing materials that do not require aseptic processing, but require moisture removal while preserving structure, and require a dried product in powder form. For example, ceramic / metallic products used in superconductors or for forming nanoparticles or microcircuit heat sinks may be produced using the herein disclosed techniques.

[0046] The systems and methods described herein may be performed in part by an industrial controller and / or computer used in conjunction with the processing equipment described herein. The equipment is controlled by one or more plant logic controllers (PLC) such as controller 390 which is shown in FIGS. 2, 3 and 5, that controls the opening and closing of various valves as discussed herein and further having processing logic for valves, motors, and the like. An interface with the PLC is provided via a PC. The PC loads a well-defined recipe to the PLC to run. The PLC will upload historical data to the PC from the run for storage. The PC may also be of use for manual control of the devices / apparatus, operating specific steps for freezing.

[0047] The PLC and the PC can include central processing units (CPU) and memory, as well as input / output (VO) interfaces connected to the CPU via a bus. The PLC is connected to the processing equipment via the I / O interfaces to receive data from sensors monitoring various conditions of the processing equipment such as temperature, position, speed, flow rate and the like. The PLC is further connected to operate devices that are part of the processing equipment.

[0048] The memory may also include random access memory (RAM) and read-only memory (ROM). The memory may also include removable media such as a disk drive, tape drive, and the like or a combination thereof. The RAM may function as a data memory that stores data used during execution of programs in the CPU, and is used as a work area. The ROM may functionas a program memory for storing one or more programs including the steps executed in the CPU. The program may reside on the ROM, and may be stored on the removable media or on any other non-volatile computer-usable medium in the PLC or the PC, or computer readable instructions stored thereon for execution by the CPU or other processor (including ASIC) to perform the methods disclosed herein.

[0049] With reference to FIGS. 2-5, an exemplary direct contact spray freezing system 200 is partially shown in accordance with aspects of the present invention. In brief, the spray freezing system 200 is defined by a freezing vessel or tower 204, a liquid product delivery subsystem 240 for delivering a bulk product in liquid form to the confines of the freezing tower 204, and a coolant fluid delivery subsystem 280 for delivering a coolant fluid to the confines of the freezing tower 204. Each of the foregoing will now be described in greater detail. This exemplary apparatus further includes a dryer chamber, which is described in a later portion of this Detailed Description.

[0050] First, the freezing tower 204 is defined by a structure having a defined and vertically extending interior cavity (herein also referred to as a freezing chamber 208), which further includes an inner circumferential sidewall 212 and an outer circumferential sidewall 216, and further including an upper portion 220. According to at least one version, a cavity or spacing can be formed between the inner and outer sidewalls 212, 216. Preferably, the freezing tower 204 is well- insulated such as within the afore mentioned cavity between the inner and outer circumferential sidewalls 212, 216, for example, vacuum insulated or other suitable techniques, in order to maintain a sufficiently cold environment within the defined interior chamber 208 for the delivered coolant fluid and product, and which as described in greater detail below, maximizes the duration of a coolant fluid (liquid nitrogen) microdroplet as a liquid before evaporation due to heat leak.

[0051] The upper or top portion 220 of the herein described apparatus 200 is a prilling section, which is configured to retain one or more vertically disposed nozzles 324, the latter forming a portion of a vibratory droplet generator 320.

[0052] The product delivery subsystem 240 is defined by a product source or reservoir 244 that is linked through one or more connective passageways or conduits 248 and one or more valves 252, such as gate valves, to the vibratory droplet generator 320, which includes a corresponding number of droplet nozzles 324. According to this specific embodiment, a total of four (4) vertically extending droplet nozzles 324 are separately linked by respective passageways 248 and valves 252to the product reservoir 244, as shown in spaced relation in FIG. 4(A). Each droplet nozzle 324 is preferably configured to receive the same flow rate from the product reservoir 244, wherein flow monitoring of each flow path / passageway 248 may be monitored via a flow meter (not shown). Additionally, each fluid flow path can be hard piped, or alternatively couplable tubing can be used that is configured for single use or single product use.

[0053] In this embodiment and with reference to FIG. 4(B), a vibratory drive motor 328 is connected via an extension 329, such as a connecting rod, leading from the drive motor 328 to a nozzle disc 330 upon which the droplet nozzles 324 are mounted through openings that are formed in the disc 330. According to the herein described embodiment, the nozzle disc 330 is made from metal. Each of the fluid flow paths from the product reservoir is connected directly to a corresponding droplet nozzles(s) 324 by a flexible element which does not impede the vibration of the vibrating nozzle disc 330, as driven by the vibratory drive motor 328. According to one version, the nozzle disc 330 is connected to a flexible diaphragm 334 to create a physical barrier between the nozzle tip(s) in the sterile environment / space 336 of the freezing tower 204 and the tubing / vibratory drive motor 328 in the non-sterile space. The product delivered to each droplet nozzle 324 is forced through an orifice by pressure and the separated from the nozzle tip by the vibration of the nozzle body and gravity to create individual droplets or product beads. Typical drive frequencies are in the range of about 2000 Hz. By controlling the vibratory rate, and the orifice size of each droplet nozzle 324, the product bead size may be altered. Typical nozzle diameters to produce a 600 um bead are on the order of about 150 microns. Summarily, the vibratory droplet generator 320 produces uniform product droplets having a relatively tight and narrow size distribution that are caused to fall downwardly under gravity along a vertical trajectory toward the bottom of the freezing tower 204. The production of controlled and predictable product droplets is important in drying and filling of the bead material.

[0054] According to this specific embodiment, the product delivery subsystem 240 further includes a chiller 250, which is coupled to the product reservoir 244 via respective inlet and outlet passageways 254, 256. The outlet passageway 256 further includes a valve 258 wherein the chiller 250 is configured to keep the stored bulk product at a controlled temperature prior to delivery of product to the freezing tower 204. In addition and according to this embodiment, a dry gas, such as nitrogen gas (N2), is provided from an appropriate source 262 and can be directed to the product reservoir 244 via a passageway or conduit 264 as regulated by a valve 268, wherein the gas is firstpassed through a filter 266 that is intermediately disposed between the source of gas 262 and the product reservoir 244 to create a sterile gas. In accordance with this embodiment, the bulk product is temporarily stored in the product reservoir 244. Sterile nitrogen, that is, the nitrogen gas that passes through the filter 266, is delivered to the product reservoir 244 to pressurize the vessel, in order to ensure consistent feeding of the stored bulk product liquid solution and delivery of the liquid product to the vibratory droplet generator 320. As noted, the product reservoir 244 may optionally be in communication with an external cooling device, such as the chiller 250, in order to maintain the liquid product within a specific non-freezing temperature range prior to entering the freezing tower 204.

[0055] The coolant delivery system 280 according to this exemplary embodiment includes one or more coolant nozzles 284 that are linked via conduits or passageways 288, 289 from a source of coolant fluid 292, which according to this specific embodiment contains liquid nitrogen (LN2), as controlled by a shut off valve 294. The one or more coolant nozzles 284 are disposed in the upper portion 220 of the freezing tower 204 beneath the vibratory droplet generator 320, creating a gas pocket therebetween, but it will be understood that the locations of these latter nozzles can be suitably varied within the chamber 208. The formed gas pocket is intended to keep the droplet nozzles 324 warmer, and therefore prevent bulk product from freezing prior to delivery. Alternatively and in lieu of the formed air pocket, a nozzle heater (not shown) can be provided. It will be understood, however, that use of a nozzle heater could adversely and inconsistently influence the controlled product temperature. According to yet another alternative, a separate gas line (not shown) could be provided between the coolant nozzle(s) 289 and the vibratory nozzles 324 in order to create positive pressure against the vibratory nozzles 324.

[0056] According to this embodiment and prior to injection of coolant fluid into the freezing tower 204, the coolant fluid must be rendered aseptic (i.e. be sterilized) To accomplish this, a dry gas (nitrogen gas N2) is further provided from a source 296 and directed via a passageway or fluid conduit 300 through a filter 298 to create a sterile gas, with the flow of the sterile gas being regulated by a valve 302. The sterile gas and the coolant fluid are each directed via their respective passageways 300, 289 to an intermediately disposed heat exchanger 304 in order to condense the gas into its liquid form. In this embodiment, the gas travels through a coil of the heat exchanger 304 that is submerged within the liquid nitrogen. The submerged coil isolates the sterile gas from the non-sterile liquid, while also allowing heat exchange to occur. Gasoriginating from the evaporation of the coolant fluid from source 292 is removed from the heat exchanger 304 via a passageway 308 to a vent 312 and the now sterile coolant fluid (LN2) is directed to the freezing tower 204 and more specifically, the coolant nozzles 284 via the passageway 288. Further details relating to the foregoing process is provided in U.S. Patent No. 10,444,109, assigned to Linde Air Products, which is herein incorporated by reference in relevant part.

[0057] According to this exemplary embodiment and before the introduction of the product droplets into the interior chamber 208 of the freezing tower 204, it is preferable for the processing atmosphere to be preconditioned within the freezing chamber 208. This preconditioning of the freezing chamber 208 is preferably done in order to establish stable and homogenous conditions throughout the volume of the interior chamber 208 and hence, insure the quality of the freezing process prior to the injection of liquid droplets. More specifically, the preconditioning minimizes product loss at the start of the freezing process and improves overall product yield. Moreover and during preconditioning, air is evacuated from the passageway 288, with oxygen removal from the freezing tower 204 and reduced humidity being advantageous results. A stable temperature is achieved, wherein the freezing chamber 208 is effectively filled with sterile LN2, stabilizing the operation of the coolant nozzle(s) 284. This processing step also enables greater overall consistency in the freezing process.

[0058] This conditioning is accomplished by spraying the same sterile liquid nitrogen used for freezing through the nozzle 284 as well as one or more additional nozzle(s) 340, which may be of a higher flow rate than the nozzle(s) 284, in order to pre-cool the freezing chamber 208 in a reasonable amount of time, this spray being shown schematically as 346 in FIG. 3. The passageway 288 extends from the coolant nozzle 284 to the additional nozzle(s) 340 (one shown in FIG. 4(b)), which further includes a shut off valve 344. The additional nozzle(s) 340 is actively controlled by measuring an exhaust temperature of the freezing tower 204. Once the freezing tower 204 sees a temperature drop below a predetermined threshold, the additional nozzle(s) 340 are isolated via valving 344 and the flow of liquid nitrogen continues only through the nozzle(s) 284. The same nitrogen upon vaporizing on the warm surfaces of the freezing tower 204 provides for a purging of the air from the freezing system 200. The vaporized nitrogen and entrained air can be exhausted from the freezing tower 204 via a process vent 348 (not shown). Once this conditioning iscomplete, the freezing of the liquid droplets 350 vertically passing through a sub-cooled cryogenic mist 354 can commence, as shown schematically in FIG. 5.

[0059] The freezing of the falling liquid droplets occurs by direct contact of the droplets with the coolant fluid. In order to achieve this type of freezing, it is necessary to create the subcooled cryogenic mist 354, or fog, of small coolant fluid (LN2) microparticles. According to this exemplary embodiment, the sub-cooled cryogenic mist 354 is produced by the one or more cooling nozzle(s) 284 disposed beneath the vibratory droplet generator 324 within the freezing tower 204, thereby transferring the heat of vaporization from the liquid nitrogen (LN2) to the warmer product. Further, this collision between the respective liquid droplets 350 and coolant fluid (LN2) microparticles must be in a manner, where the size and velocity of the liquid nitrogen microdroplets do not significantly impact the structural integrity of the product droplets (that is, do not break or rupture the droplets), when each of the particles come into contact with one another nor affect the trajectory of the falling liquid droplets by deflecting the vertically passing liquid droplets toward or into contact with the inner circumferential side wall 212 of the freezing tower 204. The sub-cooled cryogenic mist 354, or fog, is created using a hydraulic spray nozzle capable of atomizing the liquid nitrogen, such as Spraying Systems Co., Fine Spray Nozzle, %”M series, or other suitably designed atomizing nozzle. This atomizing nozzle is capable of producing coolant fluid microdroplets in the 10 to 100 micron size, as compared to the product droplet size of nominally 600 micron size.

[0060] Accordingly, the average size of each liquid droplet 350 (e.g., 600 microns) is considerably larger than the average size of each coolant fluid (LN2) microdroplet of the formed sub-cooled cryogenic mist 354 (about 10 - 100 microns). It will be understood that other suitable ratios, those that are at least 2:1 (liquid droplet size: coolant fluid microparticle size) are preferably desired so as not to disturb the integrity of the falling product droplets, nor the falling trajectory thereof, as they pass through the sub-cooled cryogenic mist 354, as created by the cooling nozzle(s) 284.

[0061] With reference to FIGS. 6-12, a processing column 400 made in accordance with aspects of the present invention is shown. In brief, the processing column 400 according to this embodiment is made from a single unitary structure that includes a plurality of adjacent portions or chambers formed or aligned in a substantially vertical orientation or configuration and havinga substantially cylindrical configuration. Alternatively, each of the various chambers of the apparatus 400 can be assembled as one or more specific housings that are linked or coupled together by known means.

[0062] More specifically and according to this exemplary embodiment, the processing column 400 includes an upper prilling section 410, a freezing chamber 420 that is disposed directly beneath the upper prilling section 410, as well as a lower drying chamber 430, the latter being disposed directly beneath the freezing chamber 420, as shown in FIG. 7.

[0063] Aspects of the prilling section 410 and the freezing chamber 420 according to this embodiment are each adapted from FIGS. 2-5, as previously discussed, as well as cross-referenced U.S. Patent Application No. 63 / 447,388. Accordingly, the prilling section 410, as previously discussed, can include one or more nozzles, such as those shown in FIGS. 2-5, for generating droplets of aseptic product obtained from a source, such as a liquid product reservoir, through one or more connections via a product delivery subsystem wherein the temperature and pressure of the contained liquid are controlled prior to delivery / dispense using a droplet generator in the prilling section 410 that vibrates the nozzle to a specific frequency and with sufficient energy at the end of the nozzle to create a plurality of liquid droplets that fall under the force of gravity. Likewise, the freezing chamber 420 is defined as a vertical tower that includes an inner and outer circumferential sidewall 423, 425, as well as defined cavity 427 between the sidewalls. One or more nozzles (one nozzle 416 being shown) are positioned within the freezing chamber 420 and configured to spray atomized liquid nitrogen LN2, or other suitable liquid cryogen via a coolant fluid delivery subsystem such as shown in FIGS. 2-5 aseptically, as a fog or mist through which the liquid product droplets are configured to fall vertically under the force of gravity and thereby creating frozen beads. The atomized particles in the formed cryogen mist are considerably smaller in size (diameter) than the falling liquid droplets and therefore do not significantly affect the falling trajectory of the liquid droplets. Accordingly, the falling liquid droplets do not contact the inner side wall before freezing 423, FIG. 8, of the freezing chamber 420, a technical problem encountered by prior processing apparatus.

[0064] With reference to FIGS 7-9, an isolation valve 440 is utilized at or near the top of the freezing chamber 420 in order to allow the freezing chamber 420 and drying chamber 430 to be placed under vacuum for the freeze-drying process, but also isolating the prilling section 410therefrom. The isolation valve 440 is located between the prilling section 410 having the droplet generator that creates the liquid droplets, and the one or more lower mounted injection nozzles 416 of liquid nitrogen disposed in the freezing chamber 420 and utilized to freeze the product as the droplets fall under the force of gravity from the prilling section 410. According to at least one embodiment, the isolation valve 440 is formed as a disc-like member 444 made from 316 or 316L stainless steel or other suitable material, such as but not limited to high density plastics (e.g., PTFE, PEEK) or high nickel content alloys (e.g., Hastalloy), which is hingably attached 447 to an upper end of the freezing chamber 420 to enable the isolation valve 440 to move between respective engaged and open positions (the latter open position being shown in FIGS. 7-9) such that the isolation valve 440 is configured to move completely up and out of the flow path of the falling product when the isolation valve 440 is in the open position. Furthermore, the herein described arrangement will move a valve gasket 446 (the latter being located at an outer periphery of the disc-like member 444), away from the cryogenic temperatures developed in the freezing chamber 420. This movement will prevent the valve gasket 446 from cooling to near cryogenic temperature, which would make it difficult to otherwise obtain a vacuum tight seal.

[0065] It will be understood that when processing an aseptic product (cooling fluid or liquid product), it is envisioned that this entire upper area (external valve surfaces, upper cavity housing, prilling nozzles, etc.) can be sterilized via steam via CIP (Clean-in-place) and SIP (Sterilization-in place) processes, the details of such processes being known to those of ordinary skill in the field as aseptic measures.

[0066] According to at least one embodiment and as shown in FIG. 9, a condenser port 450 located at the upper portion of the freezing chamber 420, but below the upper isolation valve 440, will be present during the drying process, details of which are provided in a later portion of this Description. The condenser port 450, leading to a condensing vessel (not shown in this view), will serve as the duct through which sublimated water vapor will pass to the condenser vessel. Alternatively, the condensing vessel according to at least one version can be disposed within the cavity 427 between the inner and outer circumferential sidewalls 423, 425 of the processing column 400. In accordance with this embodiment, an isolation valve (not shown) is also preferably disposed within the condenser port 450. The sizing and shape / configuration of the condenser port 450 will be dependent on the expected drying rate of the frozen product and as such is capable of a varied number of shapes and / or configurations.

[0067] Within accordance with an embodiment and with reference to FIGS. 10-12, a lower section of the processing column of the herein described apparatus 400 serves as a drying chamber 430. The drying chamber 430 can be integral to the remainder of the processing column 400 or alternatively be coupled thereto. According to this specific embodiment, the drying chamber 430 is defined by a substantially cylindrical enclosure that includes an upper end and a lower end as well as a circumferential sidewall, the lower end further including an aseptic boundary formed by a product collecting floor 464 of the drying chamber 430. The drying chamber 430 includes each of the following components, according to this specific embodiment:

[0068] First, an optional RF blocking screen 460 is located proximate the bottom of the vertical freezing chamber 420 and forming the upper end of the dryer chamber 430. This blocking screen 460, is a substantially planar member made from an aseptically compatible material such as 316L stainless steel or a high density plastic that includes a plurality of appropriately sized holes or formed openings uniformly disposed in a mesh or similar pattern. The formed holes provide a filter, which is configured to allow the passage of frozen beads, each having a typical diameter of about 600 microns, but block the passage of microwaves (RF energy) from exiting the drying chamber 430 and into the confines of the freezing chamber 420. As an example, providing a mesh of 2.5 mm holes in the RF blocking screen 460 would allow less than 3 percent microwave leakage into the freezing chamber 420, while a 1 mm hole would limit the leakage to less than about 1 percent. According to another non-limiting example, the holes of the defined mesh are about 1 - 1.5 mm.

[0069] The floor 464 of the drying chamber 430 is configured to support the frozen beads falling under the force of gravity through the freezing chamber 420 and RF blocking screen 460 from the prilling section 410, along with any residual, un-vaporized LN2. According to this specific embodiment, the floor 464 of the drying chamber 430 is fabricated from a RF transparent material. The drying chamber 430, including the product collecting floor 464, is configured to withstand cryogenic temperatures, be compatible with an aseptic process, as well as withstand the pressure of a vessel under vacuum, and a vessel under steam sterilization pressure (30 psig). Many nonmetallic materials (such as but not limited to plastics, glass and quartz) can serve in this function and meet these requirements.

[0070] Disposed within the drying chamber 430, i.e., the defined space between the RF blocking screen 460 and the chamber floor 464, is a stirring mechanism 470. The stirring mechanism 470 according to this specific embodiment includes a rotating variable speed paddletype device 474, consisting of one or more paddles 478, that can mechanically stir the product at the floor 464 of the drying chamber 430. According to this specific embodiment, the stirring device 474 includes three (3) evenly disposed paddles 478 that are evenly disposed at 120 degree intervals that are mounted for rotation about an axis that is orthogonal to a primary axis of the processing column 400. The stirrer device 474 is disposed adjacent to the floor 464 of the drying chamber 430. According to this specific embodiment, the variable speed stirring device 474 is magnetically coupled to a drive mechanism 480 having a vertically disposed drive shaft 476 and motor (not shown) that is axially located below the chamber floor 464. It should be noted that the area below the floor 464 of the drying chamber 430, according to this specific embodiment, does not experience cryogenic temperatures or vacuum conditions of the drying process. According, this latter area beneath the floor 464 of the drying chamber 430 does not require construction in line with aseptic design principals for the cleaning and sterilization thereof.

[0071] Also located within the drying chamber 430 according to this specific embodiment is a product removal port 490. The product removal port 490 is located in the circumferential sidewall of the drying chamber 430 and is essentially flush or coplanar with the product floor 464. According to at least one version, the product removal port 490 may be oriented or suitably angled tangentially in order to receive product from the stirring mechanism 470 wherein the port 490 extends externally from the drying chamber 430 to a collection vessel (not shown). Further, the product removal port 490 may have a defined upward slope, such that product does not unintentionally migrate into the product removal port 490 prior to initiation of the drying process. In addition, the product removal port 490 preferably contains an isolation valve (not shown) in order to isolate the drying chamber 430 for vacuum conditions.

[0072] Still referring to FIGS. 10-12, and in addition to the drive mechanism 480 for the stirrer mechanism 470 and in the area below the product collecting floor 464 according to this embodiment is apparatus that is configured to generate heat energy and distribute the heat energy into the frozen product beads that are contained within the drying chamber 430 of the herein described processing column 400. In accordance with this specific embodiment, the apparatus for producing heat energy includes at least one RF energy producing generator 510, that may includemeans 514 disposed in relation to the antenna 510 and is rotatable, the latter means which may further include a drive shaft according to this embodiment that is coaxial with the drive shaft 476 of the stirrer mechanism 470. According to at least one version, the RF energy generator 510 may be used to generate a uniform RF field as RF waves that enter the drying chamber 430 through the RF transparent floor 464, but are suitably blocked from entering the freezing chamber 420 by the RF blocking screen 460. As noted, the area retaining the RF energy producing apparatus, like the stirring drive mechanism 470, is preferably housed below the floor 464 of the drying chamber, and is neither aseptic, nor is required to withstand cryogenic temperature, or vacuum conditions. According to at least one embodiment, the RF generating and / or the stirrer mechanisms can be modularly attached or replaceable.

[0073] The use of RF (microwave) energy is a nonlimiting example, meaning that other energy generating sources can be utilized. The same reference numerals are used for the following description to refer to similar components for the sake of clarity. For example and with reference to FIG. 13, there is provided a drying chamber 518 made in accordance with another embodiment. As in the preceding, the drying chamber 518 can be integral to the remainder of the processing column 400 or alternatively be coupled thereto. Also and as in the preceding version, the drying chamber 518 is defined as a substantially cylindrical enclosure having an upper end and a lower end, the enclosure being defined by a circumferential side wall, with the lower end including an aseptic boundary formed by the product collecting floor 464. In this specific version, the circumferential side wall and product collecting floor 464 form an inner wall for a defined fluid filled enclosure or cavity 520 having an outer circumferential side wall 530 and an outer lower wall 534 in spaced relation to one another. A heat transfer fluid, such as silicone oil, can be circulated through the defined cavity 520 from a source (not shown) via an inlet 540 and outlet 544 disposed on the outer lower wall 534, as shown. The drying chamber 518 according to this embodiment further includes the stirrer mechanism including drive shaft and paddles 478, which are movably disposed on the product collecting floor 464, as well as an adjacent product removal port 490. Because the drive mechanism for the paddles 478 is magnetically coupled, this arrangement permits the drying chamber 518 to be hermetically sealed from the external environment.

[0074] According to another alternative embodiment and referring to FIG. 14, a drying chamber 550 includes all of the features of the drying chamber 518, FIG. 13, including the fluidfilled enclosure 520 and double walled construction of the enclosure. In addition, an infrared (IR) radiation source 560 is disposed through the circumferential side walls of the drying chamber 550 and above the product collecting floor 464 in the upper end of the chamber. The IR source 560 includes a heating element (not shown) that is sealed within a formed housing, which is preferably aseptic. A set of power leads (not shown) are also sealed within the housing of the IR source. The IR source could be utilized as the sole source of heat energy, or as shown in FIG. 14 can be used in tandem with the fluid-circulating enclosure 520, for the purpose of sublimating the product beads.

[0075] The creation of frozen product is briefly summarized. More specifically, liquid material is provided in a receptacle, such as a reservoir preferably under controlled temperature and aseptic conditions and linked via one or more lines to the prilling portion 410 of the processing column 400 that includes a droplet generator configured to produce individual liquid droplets at a vibratory frequency that enables the droplets to form and then drop from a defined nozzle under the force of gravity. The liquid droplets fall vertically through the freezing chamber 420 and through the aseptic cryogen mist that is formed within the freezing chamber 420 and produced by one or more atomizing nozzles 416 of liquid nitrogen (LN2). As previously discussed, the liquid droplets prior to freezing have a size that is considerably larger than that of the atomized cryogenic material. Consequently, the trajectory and structural integrity of the individual liquid droplets is maintained during the freezing process. The frozen beads fall to the bottom of the freezing chamber 420 and also through the porous mesh defined in the RF blocking screen 460 and into the drying chamber 430 contacting the product collecting floor 464. In the alternative embodiments, FIGS. 13, 14, there is no RF screen required and the product beads also collect on the floor 464 of the drying chamber.

[0076] With reference to FIGS. 10-14 and once the desired amount of product in the form of beads has been frozen in the vertical freezing chamber 420 and the frozen beads have passed through the optional RF blocking plate 460, and been collected on the floor 464 of the drying chamber 430, the drying process may begin. The various steps of an exemplary drying process are now described in greater detail, as follows:System Isolation:

[0077] The first step in the freeze drying operation according to this exemplary embodiment is providing sufficient isolation of the herein defined system 400. At this time and using a controller (not shown), the upper product isolation valve 440 will be caused to close thereby isolating the prilling section 410 from vacuum. In addition and at the same time, an isolation valve (not shown) located in the LN2 delivery line to the freezing chamber 420, as well as an isolation valve (not shown) disposed within the product removal port 490 are also similarly caused to close. In addition, the valve disposed within the condenser port 450 will be caused to open. The drying chamber 430 and the vertical freezing chamber 420 are then evacuated via one or more externally mounted vacuum pumps (not shown).Product Heating and Drying

[0078] Once a predetermined pressure setpoint has been attained within the herein defined processing apparatus 400, as well as a predetermined condenser temperature, each being sensed with appropriately disposed sensors (not shown) coupled to the system controller, the generation of RF energy will begin product drying via the RF energy generator 510 and means 514 that creates a uniform RF field, which is suitably directed to the drying chamber 430. According to this specific embodiment, the stirring device 474, located within the drying chamber 430, may also be energized by the controller to assist in the unform distribution of RF energy into the frozen beaded product. The time required for the drying step, RF energy supplied, and vacuum level set point are each parameters that are developed through testing and are related to the allowed product temperature, and desired final residual moisture level. In the alternative drying chambers 518, 550, the heating (heat transfer) fluid is circulated through the defined enclosure 520 via conduction / convection and / or infrared radiation is emitted to the interior of the drying chamber 518, 550 by the IR radiation source 560 in order to effectively heat the collected product beads. Upon completion of drying, the condenser vessel (not shown) may or may not be isolated using the valve (not shown) disposed in the condenser port 450 and filtered air or nitrogen gas is admitted to the herein described system 400, returning the system to atmospheric pressure.

[0079] The dried beads may now be removed from the processing column 400. According to this specific embodiment, the removal of dried material can be attained by vacuum action, in which the dried beads are drawn from the drying chamber 430 though the adjacent product removal port 490 and more specifically to a coupled product collection container (not shown) after theisolation valve (not shown) disposed within the product removal port 190 has been reopened. Additionally, the stirring device 474 may be enabled to assist in bringing dried product in close proximity to the product removal port 490 using the paddles 478. Testing has shown that dried beads prepared according to this process are not nearly as prone to the effects of static electricity, as compared to the frozen beads. However, should static electricity prevent the efficient removal of product, one of several alternative technologies can be applied in order to deenergize the beads. Any of these various techniques, which may include but are not limited to de-ionization or UV exposure may be employed before the removal of product or during the removal of product, in order to increase the percentage of collected material.

[0080] The use of the stirring mechanism 470 described for this apparatus 400 can minimally and effectively serve at least three (3) diverse functions based on the time or step in the freeze drying process. First, the ability to stir during the freezing portion of the process can effectively minimize the possibility of product agglomeration. Second, the ability to stir during the drying portion of the process enables a greater and more evenly distribution of product with respect to the generated energy. Finally, stirring the dried product during product removal facilitates bringing the dried beads to the product removal port 490 and vacuum that is applied to the product removal port 490.

[0081] In addition the herein described apparatus is suitably configured to enable annealing of the product. During an annealing step, the product beads are warmed from its very cold frozen ultimate temperature to a value below its freezing point. The product is then held for a period to allow the re-formation of the crystal structure before re-cooling the product again. This annealing step is typically done at atmospheric pressures. To provide this step, the emitted RF energy from the RF energy generator 510 or energy generators of the alternative drying chambers 518, 550 can reheat the product to a set point, then the cooling fluid delivery system can spray cryogen in order to re-cool the product.

[0082] The herein described apparatus 400 describes a single vertical processing column configured to produce a batch of material in a short amount of time using the efficiency of volumetric heating; that is, having generated energy uniformly heat all the frozen beads at one time, versus utilizing contact with a warm surface as the means of heating.

[0083] In order to replicate continuous production, but avoid the difficulty of manipulating and transporting frozen beads that must remain frozen, it is also possible to use two or more processing towers, each of the processing towers being coupled structurally to a common center condenser and product collection container. In this manner, the product collection container receives “mini -batches” from each of two or more coupled freezing chambers on a near continuous basis. Throughput of this apparatus now closely mimics that of “continuous processing,” but without the difficulties associated with the transport and manipulation of frozen beads into and through air locks and into a vacuum tight processing.

[0084] An exemplary version of a multiple freeze drying apparatus is depicted in FIGS. 15 and 16. In this version, the apparatus 600 includes two or more processing columns 620, such as those previously discussed in FIGS. 6-14, each of which are disposed concentrically and in a circumferential pattern around a centrally located condenser vessel 640 and a centrally located product collection tower 660. According to this specific embodiment, a total of eight (8) processing columns 620 are disposed about the centrally located condenser vessel 640 in which each of the processing columns 620 include condenser ports with associated valving that selectively couple the condenser vessel 640 by vacuum with the freezing chamber and drying chamber of each coupled processing column 620. As noted, each of the processing columns 620 include prilling sections, freezing sections and drying sections or chambers that are akin to those previously described with regard to FIGS 6-14. As to the drying sections or chambers of each processing column 620, any of RF, infrared or a convective jacket can be used, also as previously described for each single processing column 620. In the event, the processing column(s) 620 utilize microwave (RF) energy as the heat transferring mechanism, an RF screen or fdter similar to 460, FIG. 10, is further disposed between each of the processing columns 620 and the central condensing vessel 640.

[0085] Product is processed in a similar manner as the single processing column of FIGS. 6-14 and as previously described, other than having the dried product drawn by vacuum into an intermediate product collection container 680 through a spoked arrangement of ports / conduits provided between the intermediate product collection container 680 and a lower section of each of the individual processing columns 620. In this manner, the product may undergo quality sampling before being transported by gravity to the centrally located product collection container 640, or rejected if quality attributes have not been met.

[0086] While the invention has been described in terms of particular variations and illustrative figures, those of ordinary skill in the art will recognize that the invention is not limited to the variations or figures described. In addition, where methods and steps described above indicate certain events occurring in certain order, those of ordinary skill in the art will recognize that the ordering of certain steps may be modified and that such modifications are in accordance with the variations of the invention. Additionally, certain of the steps may be performed concurrently in a parallel process when possible, as well as performed sequentially as described above. Therefore, to the extent there are variations of the invention, which are within the spirit of the disclosure or equivalent to the inventions found in the claims, it is the intent that this patent will cover those variations as well.

[0087] To the extent that the claims recite the phrase “at least one of’ in reference to a plurality of elements, this is intended to mean at least one or more of the listed elements, and is not limited to at least one of each element. For example, “at least one of an element A, element B, and element C,” is intended to indicate element A alone, or element B alone, or element C alone, or any combination thereof. “At least one of element A, element B, and element C” is not intended to be limited to at least one of an element A, at least one of an element B, and at least one of an element C.

[0088] This detailed description uses examples to disclose the invention, including the best mode, and also to enable any person skilled in the art to practice the invention, including making and using any devices or systems and performing any incorporated methods. The patentable scope of the invention is defined by the claims, and may include other examples that occur to those skilled in the art. Such other examples are intended to be within the scope of the claims if they have structural elements that do not differ from the literal language of the claims, or if they include equivalent structural elements with insubstantial differences from the literal language of the claims.

[0089] The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting. As used herein, the singular forms “a,” “an,” and “the” are intended to include the plural forms as well, unless the context clearly indicates otherwise. It will be further understood that the terms “comprise” (and any form of comprise, such as “comprises” and “comprising”), “have” (and any form of have, such as “has” and “having”),“include” (and any form of include, such as “includes” and “including”), and “contain” (and any form of contain, such as “contains” and “containing”) are open-ended linking verbs. As a result, a method or device that “comprises,” “has,” “includes,” or “contains” one or more steps or elements possesses those one or more steps or elements, but is not limited to possessing only those one or more steps or elements. Likewise, a step of a method or an element of a device that “comprises,” “has,” “includes,” or “contains” one or more features possesses those one or more features, but is not limited to possessing only those one or more features. Furthermore, a device or structure that is configured in a certain way is configured in at least that way, but may also be configured in ways that are not listed.

[0090] The corresponding structures, materials, acts, and equivalents of all means or step plus function elements in the claims below, if any, are intended to include any structure, material, or act for performing the function in combination with other claimed elements as specifically claimed. The description set forth herein has been presented for purposes of illustration and description, but is not intended to be exhaustive or limited to the form disclosed. Many modifications and variations will be apparent to those of ordinary skill in the art without departing from the scope and spirit of the disclosure. The embodiment was chosen and described in order to best explain the principles of one or more aspects set forth herein and the practical application, and to enable others of ordinary skill in the art to understand one or more aspects as described herein for various embodiments with various modifications as are suited to the particular use contemplated and in accordance with the following appended claims. Additional embodiments include any one of the embodiments described above and described in any and all exhibits and other materials submitted herewith, where one or more of its components, functionalities or structures is interchanged with, replaced by or augmented by one or more of the components, functionalities or structures of a different embodiment described above and as set forth in the following appended claims.Parts List for FIGS. 1 -16100 bulk freeze drying system102 product, batch104 freeze drying trays106 freeze drying chamber107 vials108 shelves110 passageway112 condensing chamber114 condensing coils116 vacuum pump118 higher pressure outlet200 direct contact spray freezing system’204 freezing tower208 cavity or chamber212 inner circumferential sidewall, freezing tower216 outer circumferential sidewall, freezing tower220 upper portion, freezing tower250 chiller252 valves254 passageway or fluid conduit256 passageway or fluid conduit262 sterile gas source264 passageway or fluid conduit266 filter268 valve280 coolant fluid delivery subsystem284 coolant nozzle288 passageway or conduit289 passageway or conduitcoolant fluid source valve gas source filter passageway or conduit valve heat exchanger passageway or conduit vent vibratory droplet generator droplet nozzle(s) vibratory drive motor extension or connecting rod nozzle disc flexible diaphragm sterile space additional coolant nozzle valve preconditioning spray of coolant fluid liquid droplets sub-cooled cryogenic mist controller freeze drying apparatus prilling section nozzle(s) freezing chamber inner circumferential sidewall outer circumferential sidewall cavity dryer chamberisolation valve disc-like member valve gasket hinge connection condenser portRF blocking plate or screen floor, dryer chamber stirrer mechanism rotating paddle-like device drive shaft paddles drive mechanism product removal port RF energy generator means drying chamber cavity or enclosure outer circumferential wall outer lower wall fluid inlet fluid outlet drying chamber infrared emitter freeze drying apparatus individual processing columns centrally located condensing vessel centrally disposed product collection container intermediate product collection container

[0091] The herein described embodiments are exemplary in nature, Accordingly, it will be readily apparent that there are a number of other modifications and variations that can be made to the herein described system and related methods, including those which are covered by the following appended claims.

Claims

Claims1. A freeze drying apparatus comprising: at least one processing column comprising: a prilling section disposed in an upper portion of the processing column, the prilling tower enabled to produce liquid droplets of a product that are caused to drop under the force of gravity; a freezing chamber disposed beneath the prilling section, the freezing tower including one or more nozzles of a liquid cryogen that produces a cryogenic mist through which the liquid droplets fall and produces a plurality of frozen beads; and a drying chamber disposed beneath the freezing chamber, the drying chamber including means for generating heat energy within the drying chamber in order to dry the plurality of frozen beads; and a condensing chamber fluidly connected to the drying chamber and configured to draw sublimated water vapor from the frozen beads under vacuum.

2. The freeze drying apparatus according to claim 1, wherein the means for generating heat energy to the drying chamber comprises a source of microwave (RF) energy.

3. The freeze drying apparatus according to claim 2, further comprising a screen disposed between the drying chamber and the freezing chamber, the screen having openings sized to permit the passage of the plurality of frozen beads, but made from a material that prevents the passage of generated RF energy to the adjacent freezing chamber.

4. The freeze drying apparatus according to claim 1, wherein the drying chamber comprises a double-walled construction incluiding an inner wall and an outer wall, wherein the means for generating heat energy to the drying chamber comprises a heating fluid that is circulated within a cavity or enclosure formed between the inner wall and the outer wall.

5. The freeze drying apparatus according to claim 1 , wherein the means for generating heat energy to the drying chamber comprises a source of infrared radiation.

6. The freeze drying apparatus according to claim 5, wherein the drying chamber comprises a double-walled construction incluiding an inner wall and an outer wall, wherein the means for generating heat energy to the drying chamber further comprises a heating fluid that is circulated within an cavity or enclosure formed between the inner wall and the outer wall.

7. The freeze drying apparatus according to claim 1, further comprising a product removal port disposed in the drying chamber.

8. The freeze drying apparatus according to claim 1, further comprising a stirrer mechanism disposed in the drying chamber.

9. The freeze drying apparatus according to claim 7, wherein the product removal port is disposed at an angle relative to a vertical axis of the apparatus.

10. The freeze drying apparatus according to claim 1, further comprising an isolation valve disposed between the prilling tower and the freezing tower.

11. The freeze drying apparatus according to claim 10, wherein the isolation valve comprises a disc-shaped member configured to hingably move about 90 degrees between an engaged position and an open position relative to a flow path of the liquid droplets.

12. The freeze drying apparatus according to claim 11 , wherein the isolation valve further comprises a seal gasket that moves between the engaged position and the open position relative to the flow path of the liquid droplets.

13. The freeze drying apparatus according to claim 1, further comprising at least one condenser port disposed between the freezing chamber and the condensing chamber.

14. The freeze drying apparatus according to claim 13, wherein the at least one condensing port includes an isolation valve.

15. The freeze drying apparatus according to claim 8, wherein the stirrer mechanism comprises a stirring device having one or more paddles disposed at a floor of the dryer chamber and a drive mechanism.

16. The freeze drying apparatus according to claim 15, wherein the stirrer mechanism assists with the movement of frozen beads to a product removal port.

17. The freeze drying apparatus according to claim 1, wherein the prilling section, freezing chamber and the dryer chamber are disposed in a single processing column, and in which the apparatus comprises a plurality of processing columns, commonly and concentrically disposed about a central condensing chamber.

18. The freeze drying apparatus according to claim 17, wherein the means for generating heat energy to the drying chamber of at least one of the plurality of processing columns comprises a source of microwave (RF) energy, and further comprising a filter that prevents the passage of generated RF energy to the central condensing chamber.

19. The freeze drying apparatus according to claim 17, wherein each of the processing columns are coupled to a product collection chamber via the product removal ports.

20. A freeze drying apparatus comprising: a center condensing chamber; and two or more processing columns disposed in relation to the center condensing chamber, each of the processing columns comprising: a prilling section disposed in an upper portion of the processing column, the prilling section enabled to produce liquid droplets of a product that are caused to drop under the force of gravity; a vertically extending freezing chamber disposed beneath the prilling section, the freezing chamber including one or more nozzles of a liquid cryogen that produces a cryogenic mist through which the liquid droplets fall and produces a plurality of frozen beads; anda drying chamber disposed beneath the freezing chamber in a lower portion of the processing column, the drying chamber including means for generating heat energy within the drying chamber and drying the frozen beads.

21. The freeze drying apparatus according to claim 20, wherein the means for generating heat energy to the drying chamber of each processing column comprises a source of microwave (RF) energy.

22. The freeze drying apparatus according to claim 21, further comprising a screen disposed between the drying chamber and the freezing chamber of each of the two or more processing columns, the screen having openings sized to permit the passage of the plurality of frozen beads, but made from a material that prevents the passage of generated RF energy to the adjacent freezing chamber.

23. The freeze drying chamber according to claim 22, further comprising a duct disposed betweeen the central processing chamber and the two or more processing columns, wherein a screen is disposed within the duct to prevent the passage of generated RF energy to the central condensing chamber.

24. The freeze drying apparatus according to claim 20, wherein the drying chamber comprises a double-walled construction incluiding an inner wall and an outer wall, wherein the means for generating heat energy to the drying chamber comprises a heating fluid that is circulated within a cavity or enclosure formed between the inner wall and the outer wall.

25. The freeze drying apparatus according to claim 20, wherein the means for generating heat energy to the drying chamber comprises a source of infrared radiation.

26. The freeze drying apparatus according to claim 25, wherein the drying chamber comprises a double-walled construction incluiding an inner wall and an outer wall, wherein the means for generating heat energy to the drying chamber further comprises a heating fluid that is circulated within an cavity or enclosure formed between the inner wall and the outer wall.

27. The freeze drying apparatus according to claim 20, wherein each of the two or more processing columns further comprises an isolation valve disposed between the freezing chamber and the prilling portion.

28. The freeze drying apparatus according to claim 20, further comprising at least one condenser port coupling the condenser chamber with each of the freezing chambers of a plurality of processing columns.

29. The freeze drying apparatus according to claim 20, wherein each drying chamber includes a stirrer mechanism.

30. The freeze drying apparatus according to claim 29, wherein each stirrer mechanism comprises a stirrer device disposed at a floor of each drying chamber and a drive mechanism.

31. The freeze drying apparatus according to claim 20, wherein each processing column further comprises a product removal port in the drying chamber.

32. The freeze drying apparatus according to claim 31, wherein each product removal port is coupled to a product delivery chamber.

33. The freeze drying apparatus according to claim 32, in which each product delivery chamber is coupled to a center product delivery chamber.

34. A method for freeze drying a product, the method comprising: dispensing a plurality of liquid droplets in vertical form under the force of gravity from a prilling chamber, each of the droplets being dispensed one at a time; creating a cryogenic mist in a freezing chamber beneath the prilling chamber that freeze the liquid droplets into a plurality of frozen beads; capturing the plurality of frozen beads in a drying chamber disposed beneath the freezing chamber; isolating the prilling chamber from the drying chamber and creating a vacuum; and heating the frozen beads in the drying chamber in which sublimated water vapor is drawn into a condensing chamber.

35. The method according to claim 34, wherein the heating of the frozen beads comprises use of microwave (RF) energy.

36. The method according to claim 34, wherein the drying chamber comprises a double-walled construction incluiding an inner wall and an outer wall, wherein the heating of the frozen beads comprises circulating a heating fluid within a cavity formed between the inner wall and the outer wall.

37. The method according to claim 34, wherein the heating of the frozen beads comprises use of infrared radiation.

38. The method of claim 34, further comprising the step of stirring the captured frozen beads in the drying chamber prior to the heating step.

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