Load path insulated and axially aligned stacked tray system for lyophilization and in-chamber mechanical closure.

Abstract

The invention relates to a stacked capsule tray system that enables the controlled transmission of axial forces generated during the drying and mechanical sealing of liquid-filled capsules, which have undergone a lyophilization process, without interfering with the vapor-permeable capsule area, via the lower tray, while structurally isolating the upper tray from the load path.

Description

1 TARIFF LOAD PATH FOR LYOPHILIZATION AND IN-CHAMBER MECHANICAL CLOSURE INSULATED AND AXIAL ALIGNMENT CONTROLLED STACKABLE TRAY SYSTEM Technical Area The invention relates to the production of liquid-filled capsules, subjected to a lyophilization process, in vapor-permeable containers. drying without interfering with the area and mechanically within the same chamber. Axial forces generated during closing are controlled via the lower tray. a stacked capsule that enables transmission and structurally isolates the upper tray from the load path It is related to the tray system. State of the Art 10 Used to improve the stability of pharmaceutical and biotechnological products. Lyophilization (freeze-drying) processes, especially for converting liquid formulations into solid form. It is one of the critical production stages that ensures its preservation. During the lyophilization process The products are generally packaged in pharmaceutical containers such as vials, syringes, cartridges, or capsules. These vessels are processed. Keeping these vessels in a vertical position throughout the process increases heat transfer by 15%. homogeneity, control of steam release and safe post-process shut-off procedures. This is of great importance. For this purpose, on the lyophilizer racks Various conveyor tray systems have been developed for use. Particularly in industrial applications where multiple container processing is required, the containers must have specific characteristics. carrier systems with top and bottom plates that enable positioning in a matrix (grid) arrangement 20 They are widely used. These systems prevent containers from tipping over and ensure alignment. It is designed to provide and optimize shelf placement. together, the lyophilization process and the chamber closure process are considered together, load transfer. and systems that comprehensively manage axial alignment control are limited. This is seen in this technical field, capsule or vial-based lyophilization and sealing 25 various patent and utility model applications and scientific studies related to their systems For example, document US7337596B2 describes the lyophilization processes. pharmaceutical containers, especially vials, should be neat, stable, and stored on lyophilizer racks. It relates to a carrier tray for repeatable positioning. The document states that... To increase the homogeneity of heat transfer during the lyophilization process, to prevent vials from tipping over or 30 designed to prevent displacement and optimize shelf placement, 2 A tray in the form of a flat plate with numerous openings is described. This tray, They are designed to be placed on the lyophilizer rack, with the base or of the vials It has geometric features that support the body sections. However, in the document in question... The axial force generated during closing is transferred to the lower tray via a specific reaction surface. No defined load path structure for its transfer is described. Furthermore, an upper carrier 5 a mechanical isolation of the element from the load path during closing There are no regulations. The document concerns the press axis during mechanical closure inside the chamber. It also does not teach alignment cooperation for aligning the cap axis. Document number US11054185B1 describes the production of injectable products through lyophilization processes. This document relates to a carrier and supporting apparatus used for a syringe or 10. Long, cylindrical pharmaceutical containers, like cartridges, are vertically placed inside the lyophilization chamber. The aim is to maintain, support, and stabilize the position. The described system, a carrier block / bottom support plate at the bottom, on which the bottom ends of the containers meet the slots, and at the top a top support that meets and secures the upper sections of the containers. It consists of a multi-part structure containing a plate. However, in this document, during closing, 15 The applied axial force passes through the capsule body via a specific annular reaction shoulder. A load path architecture that enables the transmission of the load to the lower carrier via the upper carrier is not described. the support plate does not participate in load transmission or is structurally isolated from the load path There is no instruction on how this is done. Furthermore, the mechanical connection between the press axis and the cup axis is not provided. An alignment arrangement for matching through matching elements is also 20 It is not included in the document. Document EP2694390B1 describes the use of stoppers in vial-based systems during lyophilization. a gap is left between the mouth and the container after the process is complete. The document describes a tray configuration for closing. The document details the lower tray. a base element that serves the function and a top tray / lid element placed on this element 25 A structure containing the following is described. The upper tray carries the vial closing mechanisms, and the lower tray... They are positioned to match the arrangement of vials on the tray. Together, the document in question relates to a vial-based system and its load transfer architecture. It is not defined in a deterministic way. EP2694390B1 describes what happens during shutdown. 30 that the force is transmitted only through a defined reaction surface on the lower tray There is no explicit or mandatory instruction. Load transfer during upper tray closing. No regulation is explained that structurally prevents participation; the load of the upper plate No configuration is described that would indicate mechanical isolation from the path. 3 Additionally, an alignment that ensures the press axis and the cup axis are mechanically aligned. The element or axial mating mechanism between the press and tray is also included in the document. It does not receive. In EP2694390B1, the load is transferred via a singular and axis-coinciding reaction shoulder. The transmission is not defined; there is no clear indication that the force is carried only through the lower tray. There is no doctrine for path isolation. Therefore, axial-only load path is 5. It can be defined by the transmission of axial force along the capsule axis and lateral load. This involves a system architecture that enables the structural minimization of its components. This is not explained in the document. While mechanical alignment cooperation is not explained in current systems, axis alignment is also involved. It is not mandatory. Furthermore, the known state of the technique allows for lateral moment elimination at 10. It does not teach. Current lyophilizer tray and conveyor systems process pharmaceutical vessels. contributes to its regular positioning and a certain degree of stabilization throughout mechanical sealing, especially when performed in the same chamber as the lyophilization process. certain structural and functional limitations in scenarios where operations are considered together It contains. These limitations mean that the transport / positioning elements are only for placement. 15 focusing on the function or load transfer and alignment of the shutdown operation This can arise because it does not define its requirements in a deterministic way. First, in known systems, which structure accounts for the axial force generated during closure? The loads are transported through a load path, which is often an open and necessary path. not defined; consequently, the top plate / top tray or similar intermediate elements are actually 20 It is possible that it will participate in load carrying. In such a case, the pressing force Transmission along the capsule / container axis in a purely axial manner becomes difficult, resulting in deviations from the axis. or lateral loads can occur due to tolerance concentrations and Closing accuracy and repeatability can be negatively affected. In addition, the pressing axis and the cup / capsule axis must be aligned. 25 providing a mechanically defined alignment between the tray system and the press head. In cases where cooperation is absent or this relationship is not maintained throughout the process, closure occurs. During this process, the risk of moment generation and bending can increase. This is especially true for small... in closure interfaces that operate with tolerances (e.g. cap-body lock interface, stopper-mouth interface) interface) risk of deformation, sealing problems or damage to the closing element 30 She is able to give birth. 4 On the other hand, closure elements that allow vapor to escape during the lyophilization process (for example) In applications where structures such as vented plugs or semi-permeable membranes are used, the cap area Mechanical contact or insufficient clearance can restrict steam release or This can cause damage to the closing element. Therefore, on the lid area... 5 that provides a defined free volume / axial clearance and maintains this clearance throughout the process The absence of carrier geometries is a disadvantage in terms of process reliability. It can create. Additionally, some known systems offer extra features for positioning or closing containers. The carrier components use spacer plates or closing plates; this makes the process a part of the process. Increasing the number can make the assembly / cleaning / sterilization steps more difficult and 10 Additional precautions may be required due to the risk of contamination, especially in industrial settings. In multi-container processing scenarios at scale, load transfer, alignment, and container area freedom are key considerations. The inability to meet such requirements simultaneously within a single system architecture hinders the process. This can limit repeatability and operator independence. In light of these explanations, 15 performed in the same chamber as the lyophilization process In applications where mechanical closing operations are considered together; vertically positioned containers a defined area that ensures stability and does not prevent steam from escaping over the vessel area creating a free volume, with controlled and predictable axial force generated during closing. allowing transmission via a load path and between the pressing axis and the cup / capsule axis A system architecture is needed that mechanically secures the alignment between them. 20 It is heard. In particular, it is important to determine which structural elements the load transfer occurs through. defined in this way and requiring the upper supporting element to bear the load during closing. Solutions that prevent participation are important in terms of process reliability and repeatability. It is understood that he offered. 25 Brief Description and Objectives of the Invention The invention relates to capsules containing a liquid formulation that undergoes lyophilization, in a lyophilizer. an upper and lower tray system that ensures safe and controlled processing within its container. It is related to the system in question, which ensures that the capsules are held stably in a vertical position, and vapor. preservation of the permeable vessel region and intra-chamber 30 performed after lyophilization This will enable the mechanical closing operation to be carried out with controlled load transfer. It is structured in this way. In the system in question, the pressing force is generated from the capsule cap area through the capsule body. directly to a defined reaction shoulder on the bottom tray and only through this surface It is transmitted in such a way that the upper tray creates an axial gap above the capsule cover area. It is designed so that it does not carry axial load during closing and is structurally separated from the load path. It is in an isolated configuration. Thus, the axial force is transmitted only through the capsule body. transmission is required; minimizing lateral load components and moment Its formation is structurally prevented. The system also includes a tray alignment element and an alignment sleeve located on the press head. A mechanical coupling has been defined, and thanks to this coupling, the press axis and the capsule The mounting hole axis is aligned. This arrangement ensures that axis 10 is aligned during closing. It supports pure axial load transmission by preventing misalignment. The technical effects provided by the invention include the creation of a deterministic and singular load path, and lateral load... reducing the components, preventing moment generation, at the capsule-lock interface to reduce the risk of deformation, protect valve or membrane closure elements, and The goal is to increase the repeatability of the shutdown. These effects are not independent of each other; reaction 15 shoulder, top tray insulation and alignment working together These are synergistic technical results. This combination structurally defines the load path and while making it predictable, it minimizes capsule deformation and is especially important for vented capsules. It increases process safety in systems. Figures 20 Figure 1: Cross-sectional view of the lower tray. Figure 2: Cross-sectional view of the upper tray. Figure 3: View of the stacked system cross-section. Figure 4: View of the press head interaction. Figure 5: View of the load path diagram. 25 Figure 6: Cross-sectional view of the alignment cooperation between the tray system and the press head. Element Numbers in the Figures 100. Bottom tray 102. Lower tray body 104. Capsule insertion hole 30 6 106. Cylindrical guide area 108. Reaction shoulder 120th Capsule 200. Top tray 202. Upper tray body 5 204. Clarity 206. Relief pocket 210. Axial space 300. Tray alignment element 400. Press head 10 410. Alignment sleeve F. Axial Force A. Press Axis B. Axis of the capsule insertion hole Detailed Description of the Invention 15 The invention describes how capsules (120) subjected to lyophilization remain stable throughout the process. transport and mechanical sealing process carried out within the same chamber after processing. with a stacked tray system that enables controlled transmission of axial forces during operation is related to the invention, the vertical positioning of the capsules (120) and steam 20 on the container area with a load-bearing lower tray (100) that allows for alignment Creating an adjustable axial gap (210) that will not obstruct the exit and closing a non-load-carrying top tray configured not to join the load path during (200) They are used together. The upper tray (200) has a pressure contact during closing. does not form and the mentioned top tray (200) has a structural load-bearing function. It is not. 25 According to Figure 1, the bottom tray (100) consists of a bottom tray body (102) and inside this body (102). It contains at least one capsule insertion hole (104). Capsule insertion hole (104), to ensure that the capsule body is positioned vertically structured cylindrical guide area (106) and under this cylindrical guide area (106) It includes a positioned ring-shaped reaction shoulder (108). 30 The ring reaction shoulder (108) transmits axial reaction through the capsule (120) during closure. It is designed to receive the reaction of the force. In this context, the reaction shoulder (108), 7 by being configured to make contact with the lower edge of the capsule body during closing. transfer of the resulting axial load to the lower tray (100) in the direction of the capsule axis It provides. The load path created by the reaction shoulder (108) during capsule closure. in a way that allows the applied force to be transmitted along the capsule axis It is defined in such a way as to coincide with the capsule axis, and thanks to this configuration, 5 is formed. Lateral moment and lateral load components are minimized. In one application, closure the lateral force component transmitted to the capsule during this process, along the capsule axis A load distribution is obtained such that the ratio of the transmitted axial force component to the load distribution is less than 10%. is being done. If there is more than one capsule placement hole (104) on the bottom tray (100), the word 10 The subject is capsule placement holes (104) preferably in row-column arrangement (grid) can be inserted. The diameter of each capsule insertion hole (104) is relative to the outer diameter of the capsule. It can be determined in such a way as to provide a defined radial space. Thus the capsule (120) lateral load due to tolerance concentrations while held in a vertical position without compression Its formation can also be reduced. In this context, the radial gap is in the range of 0.05-1.00 mm or 15 The thickness can be selected as 0.15–0.30 mm. However, these values ​​may vary depending on the application. It can be differentiated. Figure 2 shows the configuration of the upper tray (200). The aforementioned upper tray (200) is an upper The tray body (202) and capsule (120) contain the opening (204) corresponding to the container area. Within the opening (204), 20 axial space (210) will be created on the capsule area. A circular relief pocket (206) is arranged. Thus, the capsule lid with the upper tray (200) A free space / gap is created between the zones that will not come into contact with the closing elements. Thanks to the axial clearance (210) provided by the relief pocket (206), the top tray during closing (200) does not participate in axial load bearing, in other words, the top tray (200) does not carry load. It functions as an alignment element. With this configuration, the load path is only the bottom tray (100) 25 It is defined deterministically via and mechanically from the load path of the upper tray (200). It is isolated. Axial space (210) preferably has a vent plug, semi-permeable membrane or similar vapor permeable sealing elements to prevent vapor escape throughout the process It is selected in such a way as to not restrict movement and not to create mechanical contact with the closing element. In a sample application, this axial clearance is 30 mm, preferably 1.0–1.5 mm. These values ​​can be determined. However, these values ​​depend on the capsule geometry and the closure element used. It can be changed accordingly. 8 Figure 3 shows the lower tray (100), upper tray (200) and capsule (120) together. Capsule (120), into the capsule placement hole (104) located on the lower tray (100) It is positioned so that the capsule body is in contact with the annular reaction shoulder (108). It is positioned. The upper tray (200) is the axial space (210) above the capsule's cap area. They are stacked on the bottom tray (100) to form 5 during closing. the axial force is transmitted only through the reaction shoulder (108) to the lower tray (100) It is designed to provide this. Figure 4 shows the interaction between the press head (400) and the capsule (120). Press head (400) applies an axial force (F) to the capsule area. This applied force (F), from the capsule cap region to the capsule body and from there to the circular reaction shoulder (108) 10 It is transmitted and reacted by the lower tray (100). In this context, the force path, sample It can be defined as follows: Press head (400) → capsule cap area → capsule body → reaction shoulder (108) → bottom tray (100). Since the top tray (200) does not participate in this force path, 15 from the top tray during the closing process Potential parasitic lateral loads and bending moments are minimized. Thus, pure axial load transfer is ensured on the capsule (120). Figure 5 schematically shows this deterministic load path. Here, the shutdown The axial force (F) generated during this process is carried by the lower tray (100) and the upper tray (200) It is shown that it is mechanically isolated from the load path. Thanks to this structure, the lateral load is 20 Reducing the number of components and increasing closing accuracy and process repeatability It is possible. In one application, the total applied to the capsule during closure When comparing the axial component (Fₐ) and the lateral component (Fₗ) of the force, the lateral force... a load distribution such that the ratio of the axial force component to the load component is less than 10% is obtained. 25 Figure 6 shows the alignment cooperation between the tray system and the press head (400). Tray alignment element (300) with alignment sleeve (410) located on press head (400) It is configured to match mechanically. This matching allows the press axis (A) to... The capsule insertion hole axis (B) can be geometrically aligned. Thus, the closure During this process, the possibility of axial misalignment is reduced, lateral load generation is prevented, and pure axial 30° is achieved. Compression is provided. In other words, in the system, the lower tray (100) and the press head (400) 9 at least one tray alignment element (300) providing mechanical matching between and the press head (400) with alignment sleeve (410) and press axis (A) with mechanical coupling an alignment in the structure that ensures the alignment of the capsule insertion hole axis (B) with the capsule insertion hole axis (B) The system is in place. In other words, with the applied pressure force (in the range of 50-500 N) The press axis and the capsule axis are aligned by mechanical coupling. 5 Trays (lower tray (100) and upper tray (200)) suitable for pharmaceutical production applications. They are manufactured from suitable materials. For example, stainless steel (e.g., 316L or 304). Polymer materials or equivalent materials required by the relevant application are suitable. Tray (100) and / or top tray (200) are manufactured from stainless steel material, The surfaces are subjected to electropolishing. With this process, the surface roughness is reduced to 10. This reduces contamination and ensures a hygienic surface suitable for pharmaceutical production conditions. Additionally, The tray geometry can be designed to avoid sharp corners and blind spots. The invention is not limited to the example configuration described above, but will provide the same technical effect. It also includes different geometric and structural variations. For example, as shown in Figure 1. The reaction shoulder (108) is continuous and circular in structure. However, the reaction shoulder (108) is uninterrupted 15 full ring shape, segmented ring shape, multiple contact lugs shape, conical having a stepped (stepped) structural form, with a concave or convex contact surface, or It can be formed as a hybrid structure containing elastic intermediate elements. The main function of the reaction shoulder (108) is to move the capsule body through the capsule during closure. The purpose is to transfer the transmitted axial force to the lower tray (100) so that it coincides with the capsule axis. This 20 Therefore, although the geometry of the shoulder may vary, the axial load is deterministic. The use of any contact area that allows transmission is also suitable. Reaction surface It can be planar, or conical, conforming to the geometry of the capsule's bottom edge. It can also have a rounded surface. This allows for adaptability to different capsule types. It can be provided. 25 The capsule insertion hole (104) is fully cylindrical, with a chamfered top, very with gradual diameter change, slightly conical inner surface, elastomer-supported or floating The insert can be modular. The radial clearance value is limited to the range of 0.15–0.30 mm. not, but in different ranges depending on capsule tolerances and manufacturing precision. It can be selected. The void value can also be set as a certain percentage of the capsule diameter, such as 30. It can be identified. At the bottom of the capsule insertion hole (104), the excess of the capsule body There may also be a stopper that limits its downward movement. The opening (204) on the top tray (200) and the ring relief pocket (206) are full ring in the form of a polygon, with a conical inner surface, and a multi-stage cavity geometry, or It can have a customizable insert module. Axial space (210) does not have to be a fixed distance, but depends on the capsule type. It has a changeable or adjustable structure. For example, an adjustable spacer structure, 5 Different options are available using replaceable intermediate rings, elastic buffer elements, spring or flexible modules. It can be adjusted to the container height. The top tray (200) functions as a fully non-load-bearing alignment element, however, some in applications with minimal contact points to provide only horizontal stabilization. It may have. These contact points are arranged in such a way that they do not create axial load transmission. 10 It can be positioned. The load path does not have to be defined only through the reaction shoulder (108), but also axial Alternative structures that transmit the force to the lower tray can also be used. For example; multiple reaction. surfaces, circumferential support ring, raised support platform on the lower tray or A replaceable load transfer insert can be used. The basic principle is that the upper 15 of the axial force... reacted via the lower tray (100) through the capsule body, not via tray (200) is to be taken. The tray alignment element (300) consists of a cylindrical centering pin, a conical sleeve, and a conical reference. surface, wedge (tapered wedge), magnetic alignment element, multi-point reference system or It can be configured as a rail and channel system. 20 The alignment sleeve (410) located on the press head (400) is similarly different. It can be in geometries. Press axis (A) and capsule insertion hole axis (B) The overlapping mechanism involves mechanical contact, a self-centering conical structure, a linear slide, and a screw. This can be achieved with a reference or sensor-assisted active alignment system. Bottom tray (100) and top tray (200); one-piece (monoblock), multi-piece modular, interchangeable 25 It can be produced with inserts, a lightweight honeycomb structure, and composite materials. Material selection It may vary depending on the application. Stainless steel, aluminum alloys, high performance. Polymers or equivalent pharmaceutically compatible materials may be used. The developed system is suitable for single capsules, multiple capsules, different capsule diameters, and various other applications. It can be designed to be adapted to different heights or different lyophilizer rack sizes. Bottom 30 11 tray (100) and top tray (200), stackable or modular form with multiple layers It can be used in this way. Capsules (120) include enteric capsules, gelatin capsules, HPMC capsules, and capsules containing vented plugs. The capsule can have a membrane closure structure or come in different diameters and lengths. The system is not limited to capsules only, but also includes 5 similar capsules that need to be closed with axial load. It is also adaptable to pharmaceutical containers with a body-and-cup structure. Each of these alternative configurations does not change the fundamental principle of the system. It is feasible. In these configurations, the load path passes through the capsule body. The reaction is arranged to be transmitted through a defined reaction surface on the lower tray, and the upper structural 10 from the load path so as not to participate in the force transmission generated during tray closing. It is isolated as follows: Mechanical alignment elements of the press axis and capsule axis. The possibility of overlapping via this method is preserved and contact between the capsule cover area and the upper tray is maintained. A defined axial space is maintained that does not involve different geometric shapes. Within this framework, different geometric shapes are possible. Even if structural variations can be implemented, the axial force is transferred through the lower tray. The system architecture, based on deterministic transmission, remains unchanged. 15 The invention concerns a stacked tray system for the lyophilization of capsules containing liquid formulations and the same to comprehensively support the mechanical sealing process within the chamber It is structured. Below is an example of how the system works, based on a sample application scenario. It is explained. In the first stage, capsules containing liquid formulation (120) are placed on the lower tray (100) capsule 20 The capsule body is placed vertically into the insertion holes (104). The capsule body is placed in the cylindrical guide It is guided by region (106) and its lower part is on the circular reaction shoulder (108) It sits. Thanks to this structure, the capsule (120) becomes stable in the axial direction, radial space Thanks to this, it is positioned without being compressed and aligned along the vertical axis (B). At this stage the top tray (200) may not yet be in place or 25 after placement. It can be positioned. After the capsules (120) are placed on the lower tray (100), the upper tray (200) is placed on the lower tray. They are stacked. Openings (204) on the upper tray (200) for capsule placement on the lower tray. It is positioned to align with the holes (104). During this positioning; Axial space (210) is maintained between the capsule cap area and the upper tray, annular relief 30 The pocket (206) does not come into contact with the lid area, the upper tray does not function as a load-bearing element. 12 Thus, the system achieves alignment without creating mechanical contact on the capsule area. is provided. During the lyophilization process, the bottom tray (100) and the top tray (200) are stacked on the lyophilizer rack. is being placed. During the lyophilization process, the liquid formulation inside the capsule It is frozen, then dried by sublimation, and steam is applied to the capsule area 5. It is freely discharged from the top tray (200) and the capsule cover area. Since there is a defined axial space (210); vent plug or semi-permeable membrane mechanically unobstructed, steam release is not restricted, and in the container area No deformation occurs. At this stage, the tray system is only for positioning and... It serves a stabilization function. 10 After lyophilization is complete, the capsules are sealed without being removed from the reservoir. The press head (400) is positioned to align with the tray system. Then, the tray alignment element (300) and the self-centering element on the press head The alignment sleeve (410) in the conical form matches. Thanks to this match, the press axis The axis of capsule placement hole (B) is aligned with (A), minimizing axis misalignment. In this stage, the press head (400), capsule It applies an axial force (F) to the container area. The applied axial force (F) is transmitted from the press head (400) to the capsule cap area, and from there to the capsule transmitted to the body and subsequently to the circular reaction shoulder (108) by the lower tray (100) is met. During this transmission, the upper tray (200) will not be included in the load path. It is structured so that the axial force is transferred to the lower tray via the reaction shoulder (108). This is ensured. Thus, the load path is defined via the lower tray in a cyclic structure reaction. The axial force is transmitted through the surface and along the capsule axis. This As a result of this configuration, power transmission occurs via a single, specific line, and The formation of lateral load components is limited, and the axis 25 that may occur during closure is minimized. The possibility of misalignment and deformation at the cap-body lock interface is reduced, and closing is facilitated. The repeatability of the process is increased. After the closure process is complete, the capsule body is removed via the reaction shoulder. It remains in a supported position, the upper tray has completed its alignment task without carrying any load. and the capsules can be transported safely via the tray system. 30 The system is scalable in a grid layout for multiple capsules and suitable for industrial production environments. It has a modular structure. 13 Thanks to this operating principle, the system;  It integrates lyophilization and capping processes within the same chamber.  Defines charge transfer in a deterministic manner.  Isolates the top tray from the load path.  Mechanically secures axial alignment (axial alignment tolerance 5 (Less than ±1°)  Minimizes lateral loads and moments.  Prevents damage to vent / membrane structures. The invention concerns a stackable capsule tray system for pharmaceutical and biotechnological production facilities. It can be produced on an industrial scale to be compatible with the lyophilizer systems used and 10 It is feasible. The system can be adapted to existing lyophilizer rack sizes. It offers a modular structure and is suitable for mass production processes, automatic filling and capping. They can be integrated into production lines. Lower tray (100) and upper tray (200), pharmaceutical production manufactured from materials that conform to standards (e.g., stainless steel or suitable polymers) It can be processed and cleaning, sterilization and validation procedures that comply with GMP requirements are 15. It is suitable. The invention relates particularly to the lyophilization of capsules containing liquid formulations and the same reservoir. in production lines where mechanical closing operations are performed, process It can be directly applied to increase its reliability and repeatability. It is suitable for industrial production environments that require multiple capsule processing. It offers a scalable solution. 20 In one application, all contact points with the bottom tray (100), top tray (200) and press head (400). surfaces, Good Manufacturing Practices (GMP) used in pharmaceutical production environments It is manufactured from materials that meet the requirements. In this context, system components Low particle emission, corrosion resistant, cleanable and suitable for sterilization. 25 made of stainless steel, pharmaceutical-grade polymer, or equivalent GMP-compliant materials. is selected.

Claims

14 REQUESTS 1. Processing of liquid-filled capsules subjected to lyophilization within the reservoir. and a stackable tray system for mechanical closure within the same container, feature;  lower tray body (102) and at least one 5 located inside the lower tray body (102) capsule insertion hole (104) containing capsule insertion hole (104) capsule cylindrical guide area that enables the body to be positioned vertically (106) and positioned under the cylindrical guide area (106); capsule arranged to make contact with the lower edge of the body and during closing A reaction shoulder (108) that counteracts the axial force transmitted through the capsule 10 containing, the lower tray of axial force transmitted through the capsule during closing. The lower tray (100) is designed to be supported by the body (102),  at least one opening corresponding to the upper tray body (202) and the capsule cover area Axial space on the capsule cap region within the opening (204) containing (204). (210) has a relief pocket (206) with depth to create and close 15 axial force between the reaction shoulder (108) and the capsule cap region during The top tray (200) is stacked on top of the bottom tray (100) so as not to create transmission,  at least one that provides a mechanical connection between the lower tray (100) and the press head (400) Alignment on tray alignment element (300) and press head (400) 20 capsule placement with press axis (A) with mechanical coupling including sleeve (410). a structure that ensures the hole axis (B) is aligned with the applied pressure force It includes an alignment system.

2. According to Claim 1, it is a tray system, the characteristic of which is; the aforementioned capsule placement holes. (104) is that the lower tray body (102) is arranged in a row-column pattern.

3. Tray system according to claim 1 or 2, its feature is; cylindrical guide area (106), 25 The capsule is arranged in such a way as to create a radial space relative to its outer diameter.

4. Tray system according to claim 3, characterized by a radial clearance between 0.05-1.00 mm. It is the fact that.

5. According to claim 1, it is a tray system, the feature of which is; axial space (210), capsule cover 30 that will allow steam to escape from the area and will not make contact with the sealing element. It is in the structure.

6. Tray system according to claim 5, its feature is that the axial clearance (210) is at least 1.0 mm It is the fact that.

7. According to claim 1, the tray system has the characteristic of; the continuous ring reaction shoulder (108). full ring, segmented ring, multiple contact projections, conical contact surface, stepped structure, hybrid structure containing concave or convex contact surface or elastic intermediate element 5 It is in the form of...

8. According to claim 1, it is a tray system, the feature of which is that the capsule placement hole (104) is complete. Cylindrical, beveled top, with multi-stage diameter variation, slightly tapered interior. It is either surface-based or elastomer-backed.

9. According to claim 1, it is a tray system, its feature being; the relief pocket (206) full ring 10 in the form of a polygon, with a conical inner surface, and a multi-stage cavity geometry, or It has a customizable insert module.

10. Tray system according to claim 1, its feature is; axial clearance (210) adjustable spacer its structure, via replaceable intermediate ring, elastic buffer element or spring module It is adjustable. 15 11. According to claim 1, the tray system has the characteristic of being a cylindrical tray alignment element (300). centering pin, tapered sleeve, tapered reference surface, wedge shape, magnetic alignment element, multi-point reference system or rail-channel system It is the fact that.

12. According to Claim 1, it is a tray system, its feature being; the bottom tray (100) and the top tray (200) are a single 20 part, multi-part modular, with replaceable inserts, honeycomb structure, lightweight or It is made of composite material.

13. According to Claim 1, it is a tray system, characterized by the fact that the capsules mentioned are enteric capsules. gelatin capsule, HPMC capsule, capsule with vent plug or membrane closure It is a capsule with a specific structure. 25 14. The tray system according to claim 13, its characteristic is that the aforementioned axial clearance is at least 0.5 mm. It is the fact that.

15. According to Claim 1, it is a tray system, the feature of which is; the mentioned upper tray (200) and / or lower The tray (100) is made of stainless steel.

16. Tray system according to Claim 1, its feature is; bottom tray (100) and / or top tray (200) 30 The surfaces are metal surfaces that have undergone an electropolishing process. 16 17. It is a tray system according to Claim 1, and its characteristic is that the mentioned pressing force is 50-500 N. It is within the range.

18. According to claim 1, it is a tray system, the characteristic of which is that it transmits to the capsule during closing. lateral force component, axial force transmitted along the capsule axis It is structured so that its component is less than 10%. 5 19. According to Claim 1, it is a tray system, its feature being; lower tray (100), upper tray (200) and / or press head (400) components suitable for pharmaceutical production environments, GMP requirements It is made of materials that meet the requirements.