Heating device for rotary drum freeze-dryer

Abstract

A heating device (124) for heating particles to be freeze-dried in a rotary drum (102) of a freeze-dryer (100) is provided, the device comprising at least one radiation emitter (202) for applying radiation heat to the particles, and a tube-shaped separator (204) for separating the particles from the at least one emitter (202), The separator (202) being integrally closed at one end and separating an emitter volume (206) encompassing the at least one emitter (202) from a drum process volume (126) inside the drum (102), wherein the heating device (124) protrudes into the drum process volume (126) such that said integrally closed end of the separator (204) is arranged inside the drum (102) as a free end.

Claims

1. A rotary drum with a heater for heating particles to be freeze-dried in a freeze-dryer, the heater protruding into a drum process volume inside the drum and comprising: at least one radiation emitter for applying radiation heat to the particles; and a tube-shaped separator for separating the particles from the at least one radiation emitter, with an emitter volume encompassing the at least one radiation emitter and being separated from the drum process volume; the separator comprising a cooling supply channel and a cooling exhaust channel, said separator having a first end protruding into the drum process volume inside the drum, said separator first end hermetically sealing the emitter volume at said first end against the drum process volume, and said separator having a second end closed by a flange hermetically sealing the emitter volume at said second end against the drum process volume and an exterior of the drum; wherein a cooling medium is conveyed through said cooling supply channel and said cooling exhaust channel for cooling at least parts of the heater; wherein said separator includes an inner tube and an outer tube and wherein an outer sub-volume is provided between an inner sub-volume in said inner tube and said outer tube as part of the emitter volume, wherein said separator includes an internal partitioning wall subdividing said outer sub-volume into an upper, outer sub-volume and a lower, outer sub-volume, and wherein said cooling supply channel and said cooling exhaust channel are configured to convey said cooling medium through at least two of said inner sub-volume; said upper, outer sub-volume; and said lower, outer sub-volume.

2. The rotary drum according to claim 1, wherein the outer sub-volume between the inner tube and the outer tube is an annular space.

3. The rotary drum according to claim 1, wherein the radiation emitter is arranged inside the inner tube.

4. The rotary drum according to claim 1, wherein the cooling medium is also conveyed through the inner sub-volume of the separator.

5. The rotary drum according to claim 1, wherein the cooling medium cools a surface of the heater facing the drum process volume.

6. The rotary drum according to claim 1, wherein the cooling medium, during operation of the at least one radiation emitter, cools the separator to a temperature below a melting temperature of the particles to be freeze-dried.

7. The rotary drum according to claim 1, wherein the cooling medium, during operation of the at least one radiation emitter, keeps the separator at an average current temperature of the particles to be freeze-dried within the drum.

8. The rotary drum according to claim 1, wherein the cooling medium, during operation of the at least one radiation emitter, keeps the separator at an optimum temperature for a freeze-drying process.

9. The rotary drum according to claim 1, wherein the inner tube and the outer tube of the separator are concentrically arranged relative to each other.

10. The rotary drum according to claim 1, wherein said cooling supply channel and said cooling exhaust channel are configured to convey the cooling medium: in a forward direction through said lower, outer sub-volume; and in a backward direction through said upper, outer sub-volume.

11. The rotary drum according to claim 1, wherein the cooling medium is supplied by the cooling supply channel.

12. The rotary drum according to claim 1, wherein, after being conveyed through the separator, the cooling medium is removed from said separator through said cooling exhaust channel.

13. The rotary drum according to claim 1, wherein the cooling medium is conveyed through the separator by means of a separator cooling mechanism, the cooling mechanism including at least said cooling supply channel and said cooling exhaust channel.

14. The rotary drum according to claim 1, wherein the separator is at least in part transmissive for the radiation from the radiation emitter to enter the drum process volume.

15. The rotary drum according to claim 14, wherein the separator is made at least in part of glass material.

16. The rotary drum according to claim 1, wherein the inner and outer tubes are glass tubes.

17. The rotary drum according to claim 1, wherein a reflector is provided inside the separator for directing the radiation heat generated by the radiation emitter.

18. The rotary drum according to claim 17, wherein the reflector at least partly covers the radiation emitter.

19. The rotary drum according to claim 1, wherein the separator is integrally closed at said first end, with said integrally closed end of the separator protruding into the drum process volume inside the drum as a free end.

20. The rotary drum according to claim 1, wherein said cooling medium is provided to said inner sub-volume by said cooling supply channel and is removed from said outer tube by said cooling exhaust channel.

21. The rotary drum according to claim 1, wherein the cooling medium comprises at least one of air and nitrogen.

22. The rotary drum according to claim 1, wherein the cooling medium comprises a non-flammable medium.

23. The rotary drum according to claim 1, wherein the cooling medium comprises a liquid cooling medium.

24. A rotary-drum freeze-dryer for the bulkware production of freeze-dried particles, comprising the rotary drum with the heater according to claim 1, said freeze-dryer including a wall section adapted to hold said heater protruding inside the drum process volume inside the drum of the freeze-dryer.

25. The freeze-dryer according to claim 24, wherein the heater is fully sealed to the drum and an exterior of the drum.

Description

BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS

(1) Further aspects and advantages of the invention will become apparent from the following description of explanatory example and preferred embodiments as illustrated in the figures, in which:

(2) FIG. 1 is a cross-sectional illustration of an explanatory example of a rotary drum based freeze-dryer including a heating device;

(3) FIG. 2 is a perspective illustration of the heating device of the freeze-dryer of FIG. 1;

(4) FIG. 3 is a plan view onto components of the heating device of FIG. 2;

(5) FIG. 4 is a cross-sectional view of the separator of the heating device from the preceding figures;

(6) FIGS. 5A, 5B, 5C and 5D are cross-sectional views of various embodiments of separator components;

(7) FIG. 6 is a cross-sectional illustration of a preferred embodiment of a rotary drum based freeze-dryer according to the invention;

(8) FIG. 7A is an enlarged illustration of the area in FIG. 6 marked with C;

(9) FIG. 7B is an enlarged illustration of the area in FIG. 6 marked with J;

(10) FIG. 8A is an enlarged cross-sectional illustration of the heating device of FIG. 6 along line N-N;

(11) FIG. 8B is an enlarged cross-sectional illustration of the heating device of FIG. 6 along line P-P;

(12) FIG. 9A is a perspective view of the heating device of FIG. 6;

(13) FIG. 9B is a side view of the heating device of FIG. 6; and

(14) FIG. 9C is a plan view of the heating device of FIG. 6 from the left side in FIG. 6.

DETAILED DESCRIPTION OF SPECIFIC EMBODIMENTS OF THE INVENTION

(15) FIG. 1 schematically illustrates in a cross-sectional view an explanatory example 100 of a freeze-dryer comprising a rotary drum 102 supported within a housing chamber 104 by a single rotary support 106. The housing chamber 104 is implemented as a vacuum chamber and connected via opening 108 with condenser and vacuum pump 1 10. The freeze-dryer 100 is adapted for freeze-drying particles such as microparticles, preferably micropellets, under closed conditions, i.e. under conditions of sterility and/or containment.

(16) Drum 102 comprises an opening 1 12 on its rear plate 1 14 and an opening 1 16 on its front plate 1 18. Opening 116 is adapted for loading the drum 102 with particles via a transfer section 120 comprising an interior guiding tube 122 for guiding a product flow from an upstream particle storage/container and/or particle generation device (such as a spray chamber, prilling tower, and the like) into drum 102.

(17) The drum 102 comprises a heating device 124 for heating a drum process volume 126 inside the drum and a particle system (batch) 127 loaded into drum 102 via tube 122 and carried by drum 102 during freeze-drying. It is to be noted that the process volume for establishing process conditions for freeze-drying is the entire interior 128 of vacuum chamber 104, which comprises the process volume portion (drum process volume) 126 inside the drum as well as a process volume portion 130 outside the drum.

(18) A freeze-drying process can be initiated, for example, by cooling the process volume 128 to optimum temperatures for an efficient freeze-drying process, and in parallel or following thereto, establishing vacuum conditions and loading the particles 127 via guiding tube 122 into drum 102. Such cooling can be achieved by cooling equipment arranged in association with either drum 102 and/or vacuum chamber 104.

(19) During freeze-drying, vacuum pump and condenser 1 10 operate to withdraw sublimation vapor from the drum process volume 126 via openings 1 12, 116. Due to the vapor sublimation, the temperature of the particles and in the process volume 128 decreases below optimum values. Process control drives the freeze-drying process according to an optimized process regime, which requires that heat has to be applied to the particles to maintain the optimum temperature level/range for lyophilization. Conventional mechanisms of applying heat comprise, amongst others, heating an inner wall surface of drum 102. While the explanatory example of the freeze-dryer 100 as illustrated in FIGS. 1 to 5D and described here is not intended to exclude utilization of such conventional methods, the following discussion focuses on the application of heat by the heating device 124 to the particles 132.

(20) FIG. 2 illustrates in a perspective view the heating device 124 in further detail. FIG. 3 is a schematic plan view illustrating several components of heating device 124. It is noted that FIG. 2 illustrates a partial cross-section of transfer section 120 while FIG. 3 depicts only the guiding tube 122. FIG. 4 illustrates particular components of the heating device 124 in a cross-sectional view.

(21) Heating device 124 comprises a radiation emitter 202 for applying radiation heat to particles 127 (cf. FIG. 1). Heating device 124 further comprises a separator 204 for separating particles 127 from emitter 202. Separator 204 comprises a glass tube 302 of generally cylindrical form. An emitter volume 206 defined inside tube 302 is further confined by flanges 208, 210, which hermetically separate drum process volume 126 and emitter volume 206 from each other. The heating device 124 further comprises covering means 212, which in turn comprises a single pitch roof 214 and carries further equipment such as cleaning/sterilization medium access nozzles 216.

(22) The heating device 124 further comprises a supporting arm 304, which is connected to front plate 134 of vacuum chamber 104. Piping 218 is provided for: (1) supplying a cooling medium to the emitter volume 206, (2) removing the cooling medium after back flow thereof through roof 214 from the heating device 124, and (3) supplying cleaning/sterilization medium(s) to nozzles 216.

(23) Turning to the detailed configuration of heating device 124, the glass tube 302 can be made of glass with optimized transmissivity for the radiation emitted in operation by emitter 202. Emitter 202 may be an IR emitter with maximum emissivity in the range of about 1 μm to 2 μm, and glass tube 302 can be made of quartz glass with a transmissivity of 95% or more in that wavelength range. A wall thickness of glass tube 302 is preferably selected according to maximized transmissivity as well as optimized mechanical stability.

(24) The emitter 202 is supported inside emitter volume 206 by a flat steel bar 402 extending inside tube 302, wherein fasteners 404 for fastening emitter 202 are thermally decoupled from bar 402 via isolating means 406.

(25) Insofar as hermetic separation is established, even if, for example, sterile conditions in process volume 126 (128, 130) are established or maintained, it is not a necessity to establish sterile conditions in emitter volume 206.

(26) With regard to assembling flanges 208, 210 with tube 302, threadings could be provided as one option. Additionally, or alternatively, adhesive bonding can be employed, as long as any adhesive or glue used is emission-free. The explanatory example 100 illustrated in the figures implements a further solution, which can be combined with one or more of the before-mentioned options. Four steel rods 220 extend inside and along the length of the tube 302 connecting both flanges 208, 210 to each other and pulling flanges 208, 210 onto the ends of tube 302 (more or less rods of the same or a different material can be used).

(27) However, the explanatory example 100 illustrated in the FIGS. 1 to 4 implements another solution. Four steel rods 220 extend inside and along the length of the tube 302 connecting both flanges 208, 210 to each other and pulling flanges 208, 210 onto the ends of tube 302 (more or less rods of the same or a different material can be used). The “sealing” property is understood as “leakage-free” for any gaseous, liquid and/or solid matter, to be maintained for pressure differences of, for example, atmospheric conditions in the emitter volume 206, and vacuum conditions in the drum process volume 126, wherein vacuum may mean a pressure as low as 10 mbar, or 1 mbar, or 500 μbar, or 1 μbar; and also excess pressure conditions in the drum process volume 126, which may mean a pressure as high as 1.5 bar, or 2 bar, or 3 bar, or more.

(28) Any sealing means employed have to be able to withstand not only pressure, but also other conditions during freeze-drying, cleaning, etc., on the process volume 126 side as well as conditions on the emitter volume 206 side, for example, during operation of emitter 202; moreover, the sealing means have to seal these conditions from each other. Any sealing material should be absorption-resistant and, with exemplary regard to temperature conditions, should withstand low temperatures such as temperatures around −40° C. to −60° C. as well as high temperatures around +130° C. on the process volume 126 side, in order to avoid embrittling and/or attrition with risk of product pollution resulting therefrom.

(29) The outer surface of glass tube 302 facing process volume 126 is cooled in order to prevent negative impact of high operating temperatures of emitter 202 on particles 127. The cooling is achieved by adapting emitter volume 206 as a cooling volume for through-conveying a cooling medium such as unsterile air, nitrogen, etc. The air, for example, can have ambient temperature, or can be cooled, depending on desired barrier or shielding properties for separator 204. Other (nonflammable) substances could also be used. The cooling medium flows inside supporting arm 304 and an inlet provided in flange 210 into the emitter/cooling volume 206, leaves volume 206 via an outlet 222 in flange 208 and backflows via pipe 224, roof 214 and one of pipes 218, and removes in this way heat from emitter 202 during an operation thereof.

(30) In the example illustrated in FIGS. 2 to 4, the glass tube 302 is a simple straight tube with a circular cross-section, the emitter volume 206 is identical with the cooling volume, and the cooling medium streams therethrough into one direction only. However, other configurations can be contemplated. According to another example 500 illustrated in cross-section in FIG. 5A, a glass tube 502 may also have a circular outer surface 504. However, glass tube 502 comprises an internal partitioning or sub-dividing wall 506 sub-dividing the inner volume of tube 502 into an upper sub-volume or sub-tube 508 and a lower sub-volume or sub-tube 510. Such a configuration can provide high mechanical stability (and would thereby allow minimizing a wall thickness of outer walls 518 of tube 502), and provides for two sub-volumes within one tube, wherein the sub-volumes 508 and 510 may or may not be connected to each other. For example, wall 506 can have one or more openings at one or both ends of tube 500 and/or at other positions.

(31) Various employment scenarios are contemplated. An emitter 512 can be provided in lower sub-tube 510. A cooling medium can be conveyed, for example, through lower sub-tube 510 into a forward direction, as indicated by symbol 514, and can be conveyed in a back direction (symbol 516) through upper sub-rube 508. Accordingly, equipment otherwise required for back-flow of the cooling medium can be saved, wherein such equipment would have to be arranged external to tube 502, e.g. in a process volume, and therefore saving such equipment is beneficial, and can contribute to simplifying a design of the heating device and/or a cleaning/sterilization of those parts of the heating device facing a drum process volume.

(32) According to other examples, the upper sub-volume 508 may not be used for guiding any cooling medium, but can be designed as a closed volume, which can be, for example, evacuated in order to serve as an isolation volume for (passively) isolating emitter volume 510 against a surrounding drum process volume 520.

(33) Another example of a glass tube 526 is illustrated in FIG. 5B. An inner sub-volume or sub-tube 528 is encompassed by and extends inside an outer tube 530, wherein tubes 528, 530 are concentrically arranged to each other. In this example, an emitter 532 is arranged inside tube 528. The annular space 534 defined between inner 528 and outer 530 tube can be utilized as isolation volume. For example, volume 534 can be evacuated in order to isolate a surrounding drum process volume 536 from the potentially high operating temperatures of emitter 532. According to the example illustrated in FIG. 5B, a cooling medium is guided along a forward direction 538 via inner tube 528. The cooling medium has to be externally guided out of the corresponding heating device, as long as the annular space 534 is used only as isolation volume. According to another alternative, the cooling medium could be conveyed in a backward direction via volume 534.

(34) A variation of the example of FIG. 5B is illustrated with dashed lines 542 intended to indicate that annular space 534 can be sub-divided (by inner walls 542) into an upper sub-volume 544 and a lower sub-volume 546. According to one example, a cooling medium could, for example, be guided into a forward direction along sub-volume 546 and in a backward direction along sub-volume 544. Other configurations utilizing one or more of sub-volumes 548, 544 and 546 for guiding a cooling medium therethrough in one or more directions can be contemplated. According to one particular example, the sub-volume 548 can be closed with, for example, atmospheric pressure conditions, while a cooling medium is guided via sub-volumes 544 and 546 for removing heat flow via walls of tube 528 resulting from an operation of emitter 532.

(35) While in the configuration of FIG. 5B, upper and lower annular spaces 544 and 546 are illustrated with similar and rotation-symmetric cross-sections, other examples can have a different configuration. For example, an annular space may have an angular variation in width. Additionally, or alternatively, an upper and lower annular space may not necessarily be symmetrically formed. Still further, while sub-dividing walls 506, 542 extend horizon-tally in FIGS. 5A, and 5B, respectively, other configurations can be contemplated, wherein deviations from a strictly horizontal orientation can for example be selected according to a direction of an emitter radiation to be incident on the (batch) product to be heated.

(36) FIG. 5C illustrates another configuration, wherein a tube 552 with an outer circular cross-section comprises wall 554 with a varying wall thickness. Specifically, an upper portion 556 of tube 552 has larger thickness, while thickness decreases towards a lower portion 558. A capillary tube 560 is illustrated which can be used, for example, for guiding a cooling medium therethrough to cool upper portion 556 of tube 552 and thereby remove heat. In the configuration illustrated in FIG. 5C, the cooling medium is guided in a forward direction 562 through tube 560 and in a backward direction 564 through emitter volume 566 comprising emitter 568. Other options for conveying a cooling medium through one or both of tubes/volumes 560, 566 are contemplated and within the routine design variations.

(37) FIG. 5D illustrates a still further configuration. A tube 582 with circular perimeter comprises wall 584 confining emitter volume 586 which receives emitter 588. A plurality of capillary tubes 590 are embedded within wall 584. A cooling medium (e.g., a cooling liquid) can be conveyed through one or more of the capillary tubes 560 into a forward and/or a backward direction for removing operational heat of emitter 558. Additionally, or alternatively, a cooling medium can be conveyed via emitter volume 586. While capillary tubes 560 are arranged in a regular pattern within wall 554, according to other configurations, capillary tubes can be grouped, for example, to be preferably located in an upper portion of a tube wall.

(38) The tube configurations illustrated herein may additionally comprise reflecting means such as, for example, reflecting layers, such that the emitter radiation can be preferably directed to be incident on the product.

(39) Referring back to the heating device 124 illustrated in FIGS. 2 to 4, roof 214 is intended to cover separator 204 from the top. In this way, particles traversing drum process volume 126 (cf. FIG. 1) from top to bottom can be re-directed away from glass tube 302. Provision of roof 214 may loosen the cooling requirements for the separator 204, more precisely, the requirements for a maximum temperature allowable for the surface of glass tube 302 facing the drum process volume.

(40) Roof 214 has been implemented as single pitch roof, as this and similar types of covers are particularly suited for easy cleaning/sterilization within CiP/SiP concepts. Cleaning/sterilization medium access points 216 are adapted for supplying cleaning/sterilization medium for cleaning/sterilizing the heating device 124 as well as the interior of rotary drum 102. In this respect, nozzles 216 are positioned in exposed positions, on top of covering means 212.

(41) While covering means 212 is shown spaced apart from other components of heating device 124 (such as separator 204 including glass tube 302), according to other configurations, a covering means can be in immediate contact with, for example, a separator component such as a glass tube confining an emitter volume. According to one example, a covering means can be formed as an arched roof, optionally including a cooling mechanism for cooling the roof. Such covering means could at the same time function as a reflecting means for directing radiation from the emitter into desired directions.

(42) With exemplary reference to the explanatory example illustrated in FIGS. 1 to 4, each of the following ensembles can be contemplated as a trade unit. The heating device 124, with or without the supporting arm 304 (in mounted or dismounted state), with or without the front plate 134 (in mounted or dismounted state), and with or without transfer section 120 (in mounted or dismounted state); the separator 204 including glass rube 302 and flanges 208, 210 with or without internal equipment such as emitter 202; and/or the glass tube 302 with or without emitter 202.

(43) In the following, a preferred embodiment of a heating device according to the invention is described on the basis of FIGS. 6 to 9C. Here, it is to be noted that the surroundings as well as additional components or similar components of the above described explanatory example of a heating device also apply for the below described preferred embodiment of a heating device according to the invention, where appropriate, and a detailed description of the same is, thus, omitted in order to prevent redundancy. However, where applicable, descriptions from the explanatory example can be adopted to the preferred embodiment as described below. In particular, the preferred embodiment of the heating device as described in the following is applicable in the freeze-dryer as shown in FIG. 1 and described in the respective parts above.

(44) FIG. 6 is a sectional illustration (along the longitudinal axis) of a preferred embodiment of a heating device 624 in accordance with the invention. In this illustration, heating device 624 is attached to front plate 134 of vacuum chamber 104. Piping 718 similar to piping 218 in FIG. 1 is provided for: (1) supplying a cooling medium to an emitter volume 706 by a cooling supply tube 718a, (2) removing the cooling medium after back flow thereof through cooling exhaust tube 718b, and optionally (3) supplying cleaning/sterilization medium(s) to respective optional nozzles (not shown) outside emitter volume 706.

(45) Heating device 624 further comprises a separator 704 for separating particles 127 from two radiation emitters 702. Dome- or beam-shaped separator 704 consists of an elongated glass tube of generally cylindrical form, wherein the particular shape of the glass tube provides improved stability of separator 704 against high pressure, such as high pressure during sterilization. Emitter volume 706 defined inside separator 704 is further confined by closed free end 704a of separator 704 and a support plate 725, which separate drum process volume 126 and emitter volume 706 from each other. The heating device 624 optionally carries further equipment such as cleaning/sterilization medium access nozzles (not shown), similar to the explanatory example of FIGS. 1 to 4.

(46) Turning to the detailed configuration of heating device 624, the glass tube can be made of glass with optimized transmissivity for the radiation emitted in operation by emitters 702. According to various configurations, each emitter 702 may be an IR emitter with maximum emissivity in the range of about I μm to 2 μm, and separator 704 can be made of quartz glass with a transmissivity of 95% or more in that wavelength range. A wall thickness of the glass tube is preferably selected according to maximized transmissivity as well as optimized mechanical stability.

(47) As can be gathered from FIG. 6, separator 704, or better its free end 704a, is protruding into drum process volume 126, wherein the other end or base end 704b of the glass tube of separator 704 is held within a multi-component socket structure in a way such that separator 704 is held in a rotatable manner around its longitudinal axis. Thus, in a cantilevered way, heating device 624 is placed freely inside process volume 126 without the need of a mounting of end 704a of separator 704 of heating device 624 inside process volume 126, thereby making it possible in case of a failure of the heating device 624 during the freeze-drying process to exchange the heating device 624 easily.

(48) As to the particular structure of separator 704 of the preferred embodiment, base end 704b of separator 704 comprises an integrally provided rim-like ledge 705 at its end face, which ledge 705 protrudes radially outside from the main body of the glass tube of separator 704. In particular, as can be seen in enlarged detail in FIG. 7B, base end 704b of separator 704, especially above the separator ledge 705, is held inside a cylindrical isolator sleeve 730, the sleeve 730 preferably consisting at least in part of Polyoxymethylene (POM), which prohibits a direct contact between the glass tube of separator 704 and metal components of the socket structure in order to ensure tightness of heating device 624 in view of differing thermal expansion coefficients of the different structural components of heating device 624. Isolator sleeve 730 is preferably fixed on the outside of the glass tube of separator 704 by means of silicone glue or the like, in order to tightly attach sleeve 730 with the separator 704 and to provide tightness in between those components. Further, Isolator sleeve 730 is arranged inside a cylindrical bushing 750, preferably made of stainless steel, with a gap in between sleeve 730 and bushing 750. Here, compensation O-rings 735, preferably consisting of silicone or ethylene propylene diene monomer (EPDM) rubber, are arranged in respective recesses in the outer circumference of sleeve 730, wherein bushing 750 is in contact with compensation O-rings 735 on its inner circumference. Compensation O-rings 735 serve for temperature-compensation in between the components of the socket structure. With this particular structure, it is possible to avoid one of the problems occurring with heating devices as known from prior art, namely undesired exchange of ambient conditions between the inside of heating device 624 and the outside, i.e. the inside of drum 102, also referred to as leakage, which occurs between the different structural components of a heating device due to the different thermal expansion coefficients of the different structural components (metal, glass, etc.) of heating devices as known from prior art. In the preferred embodiment, on the other hand, the glass tube of separator 704 is thermally decoupled from any metal components of the heating device 624, thereby enhancing the ability to prevent leakage between the emitter volume 706 and the drum process volume 126.

(49) The bushing 750 is arranged inside a cylindrical hull 760, preferably made of stainless steel, the open end of hull 760 facing the closed free end 704a of separator 704 is closed by a cup-shaped lid 770, preferably made of stainless steel. Here, bushing 750 is held inside lid 770 in tight contact with the inner circumference of lid 770. The free end 704a penetrates lid 770 through an opening in lid 770 such that free end 704a can protrude into drum process volume 126. In order to seal the socket structure, and thereby the emitter volume 706 in view of drum process volume 126 hermetically, sealing O-ring 740a, preferably consisting of silicone or ethylene propylene diene monomer (EPDM) rubber, is arranged in between lid 770 and an end face of isolator sleeve 730. Further, in order to further seal the socket structure, sealing O-rings 740b, preferably consisting of silicone or ethylene propylene diene monomer (EPDM) rubber, are arranged in between the other end face of isolator sleeve 730 and separator ledge 705, and in between separator ledge 705 and a disc-shaped plate 751, respectively, plate 751 preferably made of stainless steel and serving as a cover for bushing 750, wherein plate 751 is in contact with the other end of bushing 750 opposite to the end of bushing 750 being closed by lid 770. Any sealing means employed have to be able to withstand not only pressure, but also other conditions during freeze-drying, cleaning, etc., on the process volume 126 side as well as conditions on the emitter volume 706 side, for example, during operation of emitters 702; moreover, the sealing means have to seal these conditions from each other. Any sealing material should be absorption-resistant and, with exemplary regard to temperature conditions, should withstand low temperatures such as temperatures around −40° C. to −60° C. as well as high temperatures around +130° C. on the process volume 126 side, in order to avoid embrittling and/or attrition with risk of product pollution resulting therefrom.

(50) With this particularly interlaced structure as described above, heating device 624 provides a kind of “outer shell” being exposed to the drum process volume 126, which outer shell basically consists of separator 704, lid 770 (together with sealing O-ring 740a arranged on the side of separator's closed end), hull 760 and front plate 134. The remaining parts of heating device 624 are basically arranged inside the vacuum-tight outer shell with the main heat generating equipment being arranged thereinside, which enables that the heating device 624 can be maintained arranged inside drum process volume 126 and that the vacuum inside drum 102 or housing chamber 104 during freeze-drying can be kept intact, while it is possible to exchange one or all of emitters 702 in case of occurrence of emitter failure or failure of any other component arranged inside the outer shell. With this particular interlaced structure of heating device 624, during occurrence of emitter failure, the product to be freeze-dried can be kept inside drum 102 along with substantially maintaining desired process conditions while one or several of damaged emitters 702 can be exchanged, there-by prohibiting generation of waste product due to discontinuance of process conditions.

(51) In the preferred embodiment, plate 751 comprises a central opening, in which one end of a cylindrical carrier sleeve 752, preferably made of stainless steel, is arranged in an attached manner in that the outer circumference of carrier sleeve 752 is in contact with the inner circumference of the opening in plate 751, thereby carrying plate 751. The other end of carrier sleeve 752 is arranged inside an opening of a cover plate 780, preferably made of stainless steel, which cover plate 780 is attached to front plate 134 of vacuum chamber 104. In order to be able to compensate a length expansion of the glass tube of separator 704 due to high temperature, cover plate 780 is attached to front plate 134 by means of bolts 781 and spring discs 782.

(52) Piping 718, i.e. its tubes as well as an electro supply pipe 790 are guided through the inner space of carrier sleeve 752 into the socket structure by means of one or several (arranged in series) pot-shaped assemblies consisting of a cylindrical inner shell 726, preferably made of POM or Polytetrafluoroethylene (PTFE) and guiding the glass tube along with preventing any kind of scratching the same, and support plate 725 which closes one end of inner shell 726 on the side of the free end 704a of separator 704, wherein support plate 725 is attached to inner shell 726 by a screw-connection or the like. Here, the tubes of piping 718 and electro supply pipe 790 are welded into support plate 725, which is preferably made of stainless steel. Further, the glass tube of separator 704 is held from its inside by one or several of the above described pot-shaped structures. With such a construction, the glass tube of separator 704 is sandwiched in between inner shell 726 and isolator sleeve 730, wherein ledge 705 is held in an axial direction in between a pack of two sealing O-rings 740b, the pack of sealing O-rings 740b being held in between isolator sleeve 730 and plate 751, and in a radial direction from the outside by means of bushing 750. Attached to cover plate 780 by means of a mounting panel 741, electro supply pipe 790 penetrates through cover plate 751, front plate 134, and the socket structure of separator 704, wherein the free end of pipe 790 directed towards free end 704a of separator 704 is attached to support plate 725. Here, pipe 790 guides electrical wiring to emitters 702 and is attached to mounting panel 741 by means of a thermo screw connection 791, i.e. a self cutting screw union connection with a cutting ring or compression ring being made of POM. With such a screw connection, it is possible to adjust the rotational angle of separator 704 around its longitudinal axis as desired, stabilized by mounting panel 741.

(53) Inside the socket structure, as can be gathered from FIGS. 1, 7A, 7B, 8A and 8B, cooling supply tube 718a penetrates support plate 725 and is connected to a rectangular cooling duct 720 provided with cooling openings 721 for guiding cooling fluid to the upper interior of separator 704 opposite the two emitters 702, i.e. emitter volume 706. As can be seen in detail in FIGS. 8A and 8B, rectangular duct 720 is arranged inside separator 704 in a way such that, in the figures, the corners of the rectangular shape are aligned with the vertical and horizontal plane. The inner surface of separator 704 facing process volume 126, and thereby the separator 704 itself, is cooled by the guided cooling fluid in order to prevent negative impact of high operating temperatures of emitters 702 on particles 127. The cooling is achieved by adapting emitter volume 706 as a cooling volume for through-conveying a cooling medium such as unsterile air, nitrogen, etc. The air, for example, can have ambient temperature, or can be cooled, depending on desired barrier or shielding properties for separator 704. Other (nonflammable) substances could also be used. The cooling medium flows inside cooling supply tube 718a to duct 720, is released through openings 721 into emitter volume 706 and leaves volume 706 via cooling exhaust tube 718b, and removes in this way heat from emitters 702 during an operation thereof.

(54) On the upper sides of duct 720, a protection roof 710, preferably made of PTFE, is attached, which roof 710 serves as a reflecting means and can consists of two separate rails each forming one slope of the roof structure, as can be seen in FIGS. 8A and 8B, or can alternatively consists of one single component, for example a buckled plate or the like. Roof 710 covers emitters 702 arranged in a minor-inverted way below roof 710 in a way such that roof 710 shields or insulates the upper part of separator 704 from the heat generated by emitters 702. Thereby, heat generated by emitters 702 can be directed by means of roof 710. Emitters 702 are also attached to duct 720, similarly to roof 710, wherein mounting means 703 for each emitter 702 are provided in a way such that emitters 702 are held in a free manner inside the glass tube of separator 704 without direct contact of any one of emitters 702 with duct 720, roof 710 or the glass tube of separator 704. The mounting means of each emitter 702 basically consist of a bracket attached to the double-barrel-shaped emitter 702, which bracket is screwed to a flange attached to a lower side face of duct 720.

(55) As can be seen in FIGS. 9A and 9B, separator 704, more specifically free end 704a of separator 704 is held in a cantilevered, rotatable way inside the socket structure as described above. Here again, as well as from FIG. 9C, it can be gathered that opening 1 16 of drum 102 is adapted for loading the drum 102 with particles via a transfer section 120 comprising an interior guiding tube 122 for guiding a product flow from an upstream particle storage/container and/or particle generation device (such as a spray chamber, prilling tower, and the like) into drum 102. Guiding tube 122 penetrates an opening 135 in front plate 134 for loading particles 127 into drum 102.

(56) With such a structure of the heating device 624 of the invention, the only material exposed to process volume 126 is the glass tube of separator 704. Thus, since no mix of materials is exposed to process volume 126, no leakage issues due to different heat expansion coefficients. Furthermore, due to the use of a monomaterial, i.e. the glass of separator 704, heating device 624 has a crevice-free design and, thus, exhibits an improved cleanability.

(57) The heating device(s) such as discussed herein can beneficially be employed for freeze-drying of, for example, sterile free-flowing frozen particles as bulkware. Embodiments of the invention can be employed in design concepts related to a production under sterile conditions and/or containment conditions. A substantial energy input as required for performing lyophilization on timescales shorter than available with conventional approaches can be provided by heating devices according to the invention employing radiation emitters. Undesired “hot spots” (points of local overheating) in contact with the process volume and therefore representing potential hazard for the particles to be freeze-dried can be eliminated by providing a separator around the emitter which can be adapted to not only separate the particles from the radiation emitter, but to also provide a barrier for any temperature “hot spot” resulting from the high-operating temperatures of the emitter.

(58) Further, the emitter volume (and/or isolation volume) provided by heating devices according to the invention can be configured to be excluded from the process volume inside the drum, such that drawbacks can be avoided such as difficult cleaning/sterilization conditions, pollution, complex cooling based on demands for a sterile cooling medium, etc. Embodiments of heating devices according to the invention are particularly suited for cost-efficient freeze-dryer design. Embodiments of heating devices according to the invention can contribute to providing simplified freeze-dryer designs. According to the preferred embodiment, a drum design can potentially be simplified as heating via an inner drum wall surface may no longer be required.

(59) Embodiments of freeze-dryers equipped with heating devices according to the invention can be employed for the generation of sterile, lyophilized, uniformly calibrated particles as bulkware. The resulting products can comprise virtually any formulation in liquid or flow-able paste state that is suitable also for conventional (e.g., shelf-type) freeze-drying processes, for example, monoclonal antibodies, protein-based APIs, DNA-based APIs, cell/tissue substances, human and animal vaccines and therapeutics, APIs for oral solid dosage forms such as APIs with low solubility/bioavailability; fast dispersible oral solid dosage forms like ODTs (orally dispersible tablets), stick-filled adaptations, etc., as well as various products in the fine chemicals and food products industries. In general, suitable flowable materials include compositions that are amenable to the benefits of the freeze-drying process (e.g., increased stability once freeze-dried).

(60) While the current invention has been described in relation to a preferred embodiment thereof, it is to be understood that this description is for illustrative purposes only.

(61) This application claims priority of European patent application EP 11 008 108.0-1266, the subject-matters of the claims of which are listed below for the sake of completeness:

(62) 1. A heating device for heating particles to be freeze-dried in a rotary drum of a freeze-dryer, the device comprising a radiation emitter for applying radiation heat to the particles; and a separator for separating the particles from the emitter, wherein the separator forms an emitter volume for encompassing the emitter, and the separator is adapted to separate the emitter volume from a drum process volume inside the drum.

(63) 2. The heating device according to item 1, wherein the separator is at least in part transmissive for the emitter radiation to enter the drum process volume.

(64) 3. The heating device according to items 1 or 2, wherein the emitter volume is hermetically separated from the drum process volume, and the hermetic separation is provided for at least one of vacuum pressure conditions and excess pressure conditions in the drum process volume.

(65) 4. The heating device according to any one of the preceding items, wherein the separator comprises a glass tube.

(66) 5. The heating device according to any one of the preceding items, further comprising a cooling mechanism for cooling at least a surface of the heating device facing the drum process volume.

(67) 6. The heating device according to item 5, wherein the cooling mechanism comprises a cooling volume for through-conveying a cooling medium.

(68) 7. The heating device according to item 6, wherein the cooling volume comprises the emitter volume.

(69) 8. The heating device according to any one of preceding items, wherein the separator comprises an isolation volume.

(70) 9. The heating device according to any one of the preceding items, wherein the separator comprises a tube including two or more sub-tubes extending at least in part in parallel along the length of the tube.

(71) 10. The heating device according to any one of the preceding items, further comprising a covering means covering the emitter volume at least in part on the top.

(72) 11. The heating device according to item 10, further comprising a cooling mechanism for cooling at least an upper surface of the covering means.

(73) 12. A separator for separating particles to be freeze-dried in a rotary drum of a freeze-dryer from a radiation emitter for applying radiation heat to the particles, wherein the separator forms an emitter volume for encompassing the emitter, and the separator is adapted to separate the emitter volume from a drum process volume inside the drum.

(74) 13. The separator according to item 12, wherein the separator comprises a glass tube with a circular cross-section, and each end of the glass tube is closed by a flange hermetically sealing the emitter volume defined inside the tube against the drum process volume.

(75) 14. A wall section of a rotary drum freeze-dryer for the bulkware production of freeze-dried particles, the section comprising a heating device for heating the particles to be freeze-dried in the rotary drum of the freeze-dryer according to any one of items 1 to 11.

(76) 15. A freeze-dryer comprising a wall section according to item 14.