A drug substance concentration system and method

Abstract

This invention discloses a pharmaceutical raw material concentration system and method, relating to the field of fine chemical raw material technology. The system includes a multi-channel heat exchanger, a first vapor-liquid separator, and a second vapor-liquid separator. The multi-channel heat exchanger is equipped with a steam channel, a steam condensate channel, a circulating water channel, a chilled water channel, a pharmaceutical raw material channel, an evaporation channel, a vapor phase evaporation channel, and a liquid phase evaporation channel. The outlet of the pharmaceutical raw material channel is connected to the inlet of the evaporation channel. The outlet of the evaporation channel is connected to the inlet of the first vapor-liquid separator via pipe A. The outlet of the vapor phase evaporation channel is connected to the inlet of the second vapor-liquid separator via pipe B. The liquid phase outlet of the first vapor-liquid separator is connected to the inlet of the liquid phase evaporation channel via pipe C. This invention solves the problems of existing pharmaceutical raw material concentration methods, such as the need for multiple equipment, high energy consumption, and significant energy waste, and develops a continuous, efficient, green, and energy-saving pharmaceutical raw material concentration system and method.

Description

Technical Field

[0001] This invention relates to the field of fine chemical raw material pharmaceutical technology, and more specifically, to a raw material pharmaceutical concentration system and method. Background Technology

[0002] The production of active pharmaceutical ingredients often involves a product concentration process. The mainstream concentration method now is the kettle-type concentration method, which uses a steam jacket to heat the concentration kettle. The product is concentrated, and the evaporated material is sent to the next process after two-stage condensation.

[0003] For example, Chinese patent CN108854119A provides an evaporation kettle for evaporating and concentrating drugs. Chinese patent CN218853493U provides equipment for concentrating drugs. By incorporating a heat-insulating mechanism, it maintains a constant temperature on the outer surface of the evaporation flask, preventing the effects of air cooling and thus improving evaporation efficiency. Simultaneously, by using absorbent sponges to wipe away hot moisture from the lower outer surface of the evaporation feet, it prevents cooling by cold air. Furthermore, the use of heat-insulating cotton and heating blocks maintains a stable outer surface temperature of the evaporation flask, further improving evaporation efficiency. Chinese patent CN212914551U, through improvements to a similar evaporation kettle, provides a rotary vane drug evaporator separator for evaporating and separating drugs.

[0004] Existing technologies have high energy consumption, require a large number of heat exchangers, and lack heat coupling between materials at different levels, resulting in a significant waste of heat energy. Summary of the Invention

[0005] To address the problems existing in the prior art, this invention provides a drug substance concentration system and method. This invention solves the problems of existing drug substance concentration methods, such as the need for numerous equipment, high energy consumption, and significant energy waste. It develops a continuous operation system and method for drug substance concentration that requires fewer equipment, has a simple process flow, and is highly efficient, green, and energy-saving. This reduces energy consumption, personnel, and investment costs during the production process.

[0006] One of the objectives of this invention is to provide a drug substance concentration system.

[0007] The active pharmaceutical ingredient concentration system of the present invention comprises:

[0008] Multi-channel heat exchanger, first vapor-liquid separator, and second vapor-liquid separator;

[0009] The multi-channel heat exchanger is equipped with a steam channel, a steam condensate channel, a circulating water channel, a chilled water channel, a raw material channel, an evaporation channel, a vapor phase evaporation channel, and a liquid phase evaporation channel.

[0010] The outlet of the steam channel is connected to the inlet of the steam condensate channel via a pipe. The outlet of the raw material channel is connected to the inlet of the evaporation channel via a pipe. The outlet of the evaporation channel is connected to the inlet of the first vapor-liquid separator via pipe A. The vapor phase outlet of the first vapor-liquid separator is connected to the inlet of the vapor phase evaporation channel via a pipe. The outlet of the vapor phase evaporation channel is connected to the inlet of the second vapor-liquid separator via pipe B. The liquid phase outlet of the first vapor-liquid separator is connected to the inlet of the liquid phase evaporation channel via pipe C. A delivery pump is installed on pipe C.

[0011] In a preferred embodiment of the present invention:

[0012] The multi-channel heat exchanger is a plate-fin heat exchanger, preferably.

[0013] The multi-channel heat exchanger includes baffles, fins, guide vanes, seals, and end caps. Fins and guide vanes are placed between adjacent baffles, and the sides are sealed with seals to form a sandwich structure, creating channels. Preferably, the guide vanes, seals, and end caps separate different heat exchange zones; more preferably,

[0014] The fins are straight or corrugated; and / or,

[0015] The distance between two adjacent partitions is 2-10mm.

[0016] In a preferred embodiment of the present invention:

[0017] The active pharmaceutical ingredient (API) channel is adjacent to the steam condensate channel and the distillation liquid phase channel, forming a first heat exchange area for preheating the API within the API channel. Preferably, the heat exchange area between the steam condensate channel and the API channel is 5%-40% of the API channel, more preferably 10%-30%; and / or, the heat exchange area between the distillation liquid phase channel and the API channel is 20%-60% of the API channel, more preferably 30%-50%; and / or, the adjacent area between the steam condensate channel and the distillation liquid phase channel is 2%-30% of the steam condensate channel, more preferably 5%-15%.

[0018] The steam channel is adjacent to the evaporation channel, forming a second heat exchange area for heating and evaporating the active pharmaceutical ingredient within the evaporation channel. Preferably, the heat exchange area between the steam channel and the evaporation channel is 60%-100% of the evaporation channel, more preferably 70%-90%; and / or,

[0019] The vapor phase evaporation channel is adjacent to both the circulating water channel and the chilled water channel, forming a third heat exchange region for cooling the evaporated vapor phase within the vapor phase evaporation channel. Preferably, the heat exchange area between the circulating water channel and the vapor phase evaporation channel is 20%-60% of the vapor phase evaporation channel, more preferably 30%-50%; and / or, the heat exchange area between the chilled water channel and the vapor phase evaporation channel is 5%-20% of the vapor phase evaporation channel, more preferably 5%-10%; and / or, the circulating water channel and the chilled water channel are not adjacent; further preferably...

[0020] The first heat exchange region is 20%-60% of the total volume of the multi-channel heat exchanger, preferably 30%-50%, and / or the second heat exchange region is 10%-60% of the total volume of the multi-channel heat exchanger, preferably 20%-50%, and / or the third heat exchange region is 20%-50% of the total volume of the multi-channel heat exchanger, preferably 30%-40%.

[0021] In a preferred embodiment of the present invention:

[0022] The multi-channel heat exchanger is a cross-flow plate-fin heat exchanger; and / or...

[0023] The first heat exchange zone comprises three stacked layers, with the steam condensate channel and the evaporated liquid phase channel optionally positioned in the upper and lower layers of the raw material channel after partial stacking; and / or,

[0024] The second heat exchange zone comprises two stacked layers, one of which serves as a steam channel and the other as an evaporation channel; and / or,

[0025] The third heat exchange zone comprises three stacked interlayers, with the circulating water channel and the chilled water channel optionally located in the upper and lower interlayers of the vapor phase evaporation channel.

[0026] In a preferred embodiment of the present invention:

[0027] The steam condensate channel is discharged externally; and / or,

[0028] The inlet of the active pharmaceutical ingredient channel is connected to the source of the active pharmaceutical ingredient via a pipeline; and / or,

[0029] The outlet of the evaporation liquid phase channel yields a concentrated product; and / or,

[0030] The inlet of the steam passage is connected to a steam source via a steam inlet pipe, and the steam inlet pipe is equipped with a regulating valve; and / or,

[0031] A temperature sensor is installed on pipe A; and / or,

[0032] A temperature sensor is installed on pipe B; and / or,

[0033] A temperature sensor is installed on pipe C; and / or,

[0034] The outlet of the circulating water channel is connected to the circulating water return pipe, and the circulating water return pipe is equipped with a regulating valve; and / or,

[0035] The outlet of the chilled water channel is connected to the chilled water return pipe, and the chilled water return pipe is equipped with a regulating valve.

[0036] In a preferred embodiment of the present invention:

[0037] The system is equipped with an automated control unit, which includes a data acquisition module, a data processing module, and a control module connected in sequence.

[0038] The data acquisition module is electrically connected to the temperature sensors on pipes A and / or B and / or C, respectively.

[0039] The control module is electrically connected to the regulating valves on the steam inlet pipe and / or the circulating water return pipe and / or the chilled water return pipe, respectively.

[0040] A second objective of this invention is to provide a concentration method for a drug substance concentration system as described in one objective of this invention.

[0041] The concentration method of the active pharmaceutical ingredient concentration system of the present invention includes:

[0042] The active pharmaceutical ingredient (API) enters the API channel of a multi-channel heat exchanger via a pipeline for preheating, then enters the evaporation channel for further heating and evaporation. After vapor-liquid separation in the first vapor-liquid separator, the evaporated liquid phase is pumped into the evaporation liquid phase channel of the multi-channel heat exchanger to recover heat, resulting in a concentrated product that is discharged from the multi-channel heat exchanger. The evaporated vapor phase enters the evaporation vapor phase channel of the multi-channel heat exchanger to recover heat, then enters the second vapor-liquid separator. The vapor phase after vapor-liquid separation is sent to the post-processing section, while the liquid phase is sent to the recycling and reuse section. Preferably,...

[0043] The active pharmaceutical ingredient is preheated by the evaporating liquid phase and / or steam condensate in the first vapor-liquid separator, and then heated and evaporated by steam; the evaporating vapor phase in the first vapor-liquid separator is cooled by circulating water and / or chilled water.

[0044] The following solutions can be adopted:

[0045] 1) The liquid raw material to be concentrated enters the multi-channel heat exchanger through pipelines. It is first preheated in the raw material channel, and then heated in the evaporation channel, where part of the material vaporizes. The temperature of the vaporized material is regulated by controlling the amount of steam in the steam channel;

[0046] 2) The partially vaporized material enters the first vapor-liquid separator, where the concentrated raw material liquid phase is sent to the evaporation liquid phase channel of the multi-channel heat exchanger by a transfer pump for cooling, and then sent to the next process section.

[0047] 3) The vapor phase from the first vapor-liquid separator goes to the vapor phase channel of the multi-channel heat exchanger for condensation. After condensation, the fluid enters the second vapor-liquid separator. The temperature of the condensed liquid is controlled in a stratified manner with the fresh cold source circulating water and the chilled water, and is cascaded with the temperature of the concentrated raw material liquid phase to control the temperature of each main stream.

[0048] 4) The vapor phase of the second vapor-liquid separator goes to the non-condensable gas treatment system, while the liquid phase is the material distilled from the concentration process and is sent to the recycling section.

[0049] In a preferred embodiment of the present invention:

[0050] The temperature of the steam in the steam channel is 120-200℃, preferably 130-180℃, and / or the flow rate is 5-40m / s, preferably 10-30m / s; and / or,

[0051] The condensate temperature in the steam condensate channel is 180-80℃, preferably 160-90℃, and / or the flow rate is 0.2-3m / s, preferably 0.5-1.5m / s; and / or,

[0052] The temperature of the evaporating vapor phase in the vapor phase channel is 40-130℃, preferably 50-110℃; and / or, the flow rate is 2-10m / s, preferably 4-7m / s; and / or,

[0053] The temperature of the evaporating liquid phase in the evaporation liquid phase channel is 30-130℃, preferably 40-100℃; and / or, the flow rate is 0.2-3m / s, preferably 0.8-2m / s; and / or,

[0054] The temperature of the circulating water in the circulating water channel is 20-50℃, preferably 30-40℃, and / or the flow rate is 0.2-3m / s, preferably 0.5-2.5m / s; and / or,

[0055] The temperature of the chilled water in the chilled water channel is 0-30℃, preferably 5-20℃, and / or the flow rate is 0.2-3m / s, preferably 0.5-2.5m / s; and / or,

[0056] The temperature of the active pharmaceutical ingredient (API) in the API channel is 10-80℃, preferably 20-70℃, and / or the flow rate is 0.2-3 m / s, preferably 0.8-2 m / s; and / or,

[0057] The temperature in the evaporation channel is 40-120℃, preferably 50-110℃, and / or the flow rate is 0.5-5m / s, preferably 1-3m / s.

[0058] In a preferred embodiment of the present invention, the method further includes:

[0059] The automated control unit collects the temperature from the temperature sensor on pipe A via the data acquisition module. The data processing module compares this temperature with a preset value. If the temperature is lower than the preset value, the control module gradually increases the opening of the regulating valve on the steam inlet pipe until it is fully open; if the temperature is higher than the preset value, the control module gradually decreases the opening of the regulating valve on the steam inlet pipe until it is fully closed. Preferably,

[0060] The preset value of the temperature sensor on pipe A is 80-100℃; and / or,

[0061] The opening degree of the regulating valve is adjusted in the same way for both gradually increasing and gradually decreasing, preferably with the opening degree changing by 1-5° for every 1° deviation.

[0062] In a preferred embodiment of the present invention, the method further includes:

[0063] The automated control unit collects the temperature from the temperature sensor on pipe B via the data acquisition module. The data processing module compares this temperature with a preset value. If the temperature is higher than the preset value, the control module gradually increases the opening of the regulating valve on the circulating water return pipe until it is fully open. If the temperature is still higher than the preset value after the regulating valve on the circulating water return pipe is fully open, the control module opens the regulating valve on the chilled water return pipe and gradually increases its opening until it is fully open. If the temperature is lower than the preset value, the control module first gradually decreases the opening of the regulating valve on the chilled water return pipe until it is fully closed. If the temperature is still lower than the preset value after the regulating valve on the chilled water return pipe is fully closed, the control module gradually decreases the opening of the regulating valve on the circulating water return pipe until it is fully closed. Preferably,

[0064] The preset value of the temperature sensor on pipe B is 30-50℃; and / or,

[0065] The opening degree of the regulating valve on the circulating water return pipe and / or the regulating valve on the chilled water return pipe is adjusted to be the same for both gradually increasing and gradually decreasing, preferably with the opening degree changing by 1-5° for every 1° deviation; more preferably,

[0066] The automated control unit acquires the temperature from the temperature sensor on pipe C via the data acquisition module, and compares the temperature change difference on pipe C in real time via the data processing module. If the temperature change difference on pipe C is greater than a preset value, the control module sets the preset value of the temperature sensor on pipe B; more preferably,

[0067] The preset value for the temperature difference on pipe C is 5-10℃; and / or,

[0068] For every 1°C increase or decrease in temperature of the temperature sensor on pipe C, the preset value of the temperature sensor on pipe B increases or decreases by 0.2-1°C.

[0069] This invention uses temperature detection in pipes B and C. When the composition of the active pharmaceutical ingredient (API) remains relatively stable, the flow rates of circulating water and chilled water are adjusted primarily based on the temperature of pipe B, resulting in relatively stable control. However, when the API composition changes significantly, the most direct consequence is a large temperature fluctuation in pipe C. In this case, the preset value for pipe B also needs to be adjusted accordingly. The design of assigning a value to pipe B based on the temperature of pipe C can accommodate the frequent fluctuations in API composition during API production, making it more suitable for actual production needs.

[0070] This invention provides a raw material drug concentration system based on a multi-channel heat exchanger, solving the problems of existing raw material drug concentration methods such as requiring numerous equipment, high energy consumption, and significant energy waste. It develops a continuous operation method for raw material drug concentration that requires fewer equipment, has a simple process flow, and is highly efficient, green, and energy-saving. This reduces energy consumption, personnel, and investment costs during the production process. Attached Figure Description

[0071] Figure 1 This is a schematic diagram of the active pharmaceutical ingredient concentration system of Example 1;

[0072] Among them, 2-steam inlet pipe, 6-multi-channel heat exchanger, 7-circulating water return pipe, 8-chilled water return pipe, 10-second vapor-liquid separator, 15-A pipe, 17-first vapor-liquid separator, 18-B pipe, 19-transfer pump, 20-C pipe;

[0073] Figure 2 This is a diagram showing the heat exchange temperature and heat transfer volume (TQ) of the hot and cold streams in the multi-channel heat exchanger of Example 1.

[0074] Figure 3 for Figure 2 The TQ diagram of total heat matching between hot and cold fluids after fitting and optimization;

[0075] Figure 4 This diagram shows the relationship between the heat of hot and cold fluids and the locations of the hot and cold channels in the heat exchanger.

[0076] Figure 5 This is a schematic diagram showing the location of the hot and cold channels in the multi-channel heat exchanger of Example 1;

[0077] Among them, H1 is the steam channel, H2 is the steam condensate channel, C1 is the circulating water channel, C2 is the chilled water channel, C3 is the raw material channel, C4 is the evaporation channel, H3 is the vapor phase evaporation channel, and H4 is the liquid phase evaporation channel. Detailed Implementation

[0078] The present invention will now be described in detail with reference to the accompanying drawings and embodiments. It should be noted that the following embodiments are only used to further illustrate the present invention and should not be construed as limiting the scope of protection of the present invention. Some non-essential improvements and adjustments made by those skilled in the art based on the content of the present invention are still within the scope of protection of the present invention.

[0079]

Example 1

[0080] like Figure 1 As shown, a drug substance concentration system based on a multi-channel heat exchanger includes:

[0081] Multi-channel heat exchanger 6, first vapor-liquid separator 17, and second vapor-liquid separator 10;

[0082] The multi-channel heat exchanger 6 is a cross-flow eight-channel plate-fin heat exchanger. Channels are formed between adjacent fins. The fins are straight, and the distance between two adjacent fins is 5mm. Different heat exchange zones are separated by guide vanes, seals, and end caps. There are four hot channels and four cold channels, including a steam channel H1, a steam condensate channel H2, a circulating water channel C1, a chilled water channel C2, a raw material channel C3, an evaporation channel C4, a vapor phase evaporation channel H3, and a liquid phase evaporation channel H4. The heat flow stream is steam, and the cold flow streams are circulating water and chilled water. The specific flow channel table is shown in Table 1 below.

[0083] Table 1

[0084]

[0085] The outlet of steam channel H1 is connected to the inlet of steam condensate channel H2 via a pipe. The outlet of raw material channel C3 is connected to the inlet of evaporation channel C4 via a pipe. The outlet of evaporation channel C4 is connected to the inlet of the first vapor-liquid separator 17 via pipe A 15. The vapor phase outlet of the first vapor-liquid separator 17 is connected to the inlet of vapor phase evaporation channel H3 via a pipe. The outlet of vapor phase evaporation channel H3 is connected to the inlet of the second vapor-liquid separator 10 via pipe B 18. The liquid phase outlet of the first vapor-liquid separator 17 is connected to the inlet of liquid phase evaporation channel H4 via pipe C 20. A transfer pump 19 is installed on pipe C 20.

[0086] Figure 2Based on the heat transfer temperature and heat transfer TQ diagram in Table 1 above, the heat transfer of each stream is fitted and optimized: the heat transfer of each stream in the same temperature zone is superimposed to form the total heat transfer of that temperature zone, forming a TQ diagram for matching the total heat transfer of the hot and cold fluids, as shown in the figure. Figure 3 As shown; and according to Figure 4 The correspondence between the heat of the hot and cold fluids and the positions of the hot and cold channels in the heat exchanger clearly shows the heat transfer relationship between the streams: by exchanging heat within the same segment on the horizontal axis, the heat matching requirements can be met, thus allowing a schematic diagram of the positions of the hot and cold channels in a multi-channel heat exchanger to be drawn. Figure 5 .

[0087] like Figure 5 As shown, the active pharmaceutical ingredient (API) channel C3 is adjacent to both the steam condensate channel H2 and the evaporation liquid phase channel H4, forming a first heat exchange region for preheating the API within the API channel C3. The heat exchange area between the steam condensate channel H2 and the API channel C3 is 20% of the total area of ​​the API channel C3; the heat exchange area between the evaporation liquid phase channel H4 and the API channel C3 is 40% of the total area of ​​the API channel C3; the adjacent area between the steam condensate channel H2 and the evaporation liquid phase channel H4 is 12% of the total area of ​​the steam condensate channel H2. The steam channel H1 is adjacent to the evaporation channel C4, forming a second heat exchange region for heating and evaporating the API within the evaporation channel C4. The heat exchange area between the steam channel H1 and the evaporation channel C4 is... The area is 60% of the evaporation channel C4; the vapor phase evaporation channel H3 is adjacent to the circulating water channel C1 and the chilled water channel C2 respectively, forming a third heat exchange region for cooling the vapor phase evaporation in the vapor phase evaporation channel H3. The heat exchange area between the circulating water channel C1 and the vapor phase evaporation channel H3 is 40% of the vapor phase evaporation channel H3, and the heat exchange area between the chilled water channel C2 and the vapor phase evaporation channel H3 is 7% of the vapor phase evaporation channel H3. The circulating water channel C1 and the chilled water channel C2 are not adjacent; the first heat exchange region is 30% of the total volume of the multi-channel heat exchanger, the second heat exchange region is 40% of the total volume of the multi-channel heat exchanger, and the third heat exchange region is 30% of the total volume of the multi-channel heat exchanger. The first heat exchange zone consists of three stacked jackets, with the steam condensate channel H2 and the evaporating liquid phase channel H4 partially stacked and positioned in the lower jacket of the raw material channel C3; the second heat exchange zone consists of two stacked jackets, with the upper jacket being the steam channel H1 and the lower jacket being the evaporation channel C4; the third heat exchange zone consists of three stacked jackets, with the circulating water channel C1 and the chilled water channel C2 respectively positioned in the lower jacket of the evaporating vapor phase channel H3.

[0088] The outlet of steam condensate channel H2 is discharged externally; the inlet of raw material channel C3 is connected to the source of raw material through a pipeline; the outlet of evaporating liquid phase channel H4 receives concentrated product and discharges it from the multi-channel heat exchanger 6; the inlet of steam channel H1 is connected to the steam source through steam inlet pipe 2, and a regulating valve is installed on steam inlet pipe 2; a temperature sensor is installed on pipe A 15; a temperature sensor is installed on pipe B 18; a temperature sensor is installed on pipe C 20; the outlet of circulating water channel C1 is connected to circulating water return pipe 7, and a regulating valve is installed on circulating water return pipe 7; the outlet of chilled water channel C2 is connected to chilled water return pipe 8, and a regulating valve is installed on chilled water return pipe 8.

[0089] The aforementioned active pharmaceutical ingredient concentration system is equipped with an automated control unit, which includes a data acquisition module, a data processing module, and a control module connected in sequence. The data acquisition module is electrically connected to temperature sensors on pipes A 15, B 18, and C 20, respectively. The control module is electrically connected to regulating valves on steam inlet pipe 2, circulating water return pipe 7, and chilled water return pipe 8, respectively.

[0090]

Example 2

[0091] A concentration method using the active pharmaceutical ingredient concentration system of Example 1 above, comprising:

[0092] The active pharmaceutical ingredient (API) enters the API channel C3 of the multi-channel heat exchanger 6 through a pipeline for preheating, then enters the evaporation channel C4 for heating and evaporation. After vapor-liquid separation in the first vapor-liquid separator 17, the evaporated liquid phase is pumped by the transfer pump 19 into the evaporation liquid phase channel H4 of the multi-channel heat exchanger 6 to recover heat, and then the concentrated product is discharged from the multi-channel heat exchanger 6. The evaporated vapor phase enters the evaporation vapor phase channel H3 of the multi-channel heat exchanger 6 to recover heat, and then enters the second vapor-liquid separator 10. The vapor phase after vapor-liquid separation is sent to the post-processing section, and the liquid phase is sent to the recycling and reuse section.

[0093] The steam temperature in steam channel H1 is 150℃, and the flow rate is 20m / s; the steam condensate temperature in steam condensate channel H2 is 150~90℃, and the flow rate is 1m / s; the evaporation vapor phase temperature in vapor phase channel H3 is 90~40℃, and the flow rate is 5m / s; the evaporation liquid phase temperature in vapor phase channel H4 is 95~55℃, and the flow rate is 1m / s; the circulating water temperature in circulating water channel C1 is 32~37℃, and the flow rate is 1.5m / s; the chilled water temperature in chilled water channel C2 is 7~12℃, and the flow rate is 1.5m / s; the raw material drug temperature in raw material drug channel C3 is 30~60℃, and the flow rate is 1m / s; the temperature in evaporation channel C4 is 60~95℃, and the flow rate is 5m / s.

[0094] pass Figure 3The TQ diagram of the total heat matching of the hot and cold fluids after fitting and optimization shows that the temperature of C4 is only related to H1 (steam), so the evaporation temperature can be controlled by controlling the amount of steam. During the concentration process, the automatic control unit collects the temperature of the temperature sensor on pipe A 15 through the data acquisition module, and compares it with the preset value through the data processing module. If the temperature is lower than the preset value, the control module gradually increases the opening of the regulating valve on the steam inlet pipe 2 until it is fully open; if the temperature is higher than the preset value, the control module gradually decreases the opening of the regulating valve on the steam inlet pipe 2 until it is fully closed. The preset value of the temperature sensor on pipe A 15 is 95℃. The rate at which the regulating valve gradually increases and decreases is the same, and the opening changes by 3° for every 1℃ deviation.

[0095] pass Figure 3 The TQ diagram of the total heat matching of the hot and cold fluids after fitting and optimization shows that the temperature of H3 is related to the three cold streams C1, C2 and C3. However, considering the freely adjustable cold streams, the temperature of H3 can be adjusted and controlled by controlling the flow rates of C1 and C2. Considering the need for stable heat, the temperature is first regulated by adjusting the circulating water. If the temperature still cannot reach the target, the temperature is then lowered by adjusting the chilled water. The automated control unit collects the temperature from the temperature sensor on pipe B 18 via the data acquisition module. This temperature is then compared with a preset value via the data processing module. If the temperature is higher than the preset value, the control module gradually increases the opening of the regulating valve on the circulating water return pipe 7 until it is fully open. If the temperature is still higher than the preset value after the regulating valve on the circulating water return pipe 7 is fully open, the control module opens the regulating valve on the chilled water return pipe 8 and gradually increases its opening until it is fully open. If the temperature is lower than the preset value, the control module first gradually decreases the opening of the regulating valve on the chilled water return pipe 8 until it is fully closed. If the temperature is still lower than the preset value after the regulating valve on the chilled water return pipe 8 is fully closed, the control module gradually decreases the opening of the regulating valve on the circulating water return pipe 7. The regulating valve is adjusted to be fully closed; the preset value of the temperature sensor on pipe B 18 is 45℃; the regulating valves on the circulating water return pipe and the chilled water return pipe are adjusted to the same degree of gradual increase and decrease, with the opening changing by 3° for every 1℃ deviation; the automatic control unit collects the temperature of the temperature sensor on pipe C 20 through the data acquisition module, and compares the temperature change difference on pipe C 20 in real time through the data processing module. If the temperature change difference on pipe C 20 is greater than the preset value of 5℃, the control module sets the preset value of the temperature sensor on pipe B 18; for every 1℃ increase or decrease in the temperature of the temperature sensor on pipe C 20, the preset value of the temperature sensor on pipe B increases or decreases by 0.5℃.

[0096] By cascading control of the temperatures of pipe C 20 and pipe B 18, if the temperature of pipe C 20 increases, the temperature at which the steam can condense will also increase. Therefore, by cascading the temperature of pipe C 20 to assign an initial value to the temperature of pipe B 18, the effect of dynamic adjustment and energy saving can be achieved.

[0097]

Example 3

[0098] A certain active pharmaceutical ingredient (API) production facility, using the API concentration system of Example 1 and the API concentration method of Example 2 of this invention, obtained the following data:

[0099] Operation time: Continuous

[0100] Workshop staffing: 1 operator.

[0101] During operation, the process is simple, requires few equipment, is highly efficient, green and safe, has low energy consumption, a high level of automation, and low labor costs.

[0102] Comparative Example 1

[0103] A certain active pharmaceutical ingredient (API) production facility, using a traditional liquid concentrate method, obtained the following data:

[0104] Operation time: intermittent

[0105] Workshop staffing: 3 operators.

[0106] The operation requires control of one reactor and three heat exchangers. It necessitates multiple personnel and is quite complex. Furthermore, the lack of energy coupling results in high energy consumption in the process, impacting product efficiency.

Claims

1. A drug substance concentration system, characterized in that... The system includes: Multi-channel heat exchanger, first vapor-liquid separator, and second vapor-liquid separator; The multi-channel heat exchanger is equipped with a steam channel, a steam condensate channel, a circulating water channel, a chilled water channel, a raw material channel, an evaporation channel, a vapor phase evaporation channel, and a liquid phase evaporation channel. The outlet of the steam channel is connected to the inlet of the steam condensate channel via a pipe. The outlet of the raw material channel is connected to the inlet of the evaporation channel via a pipe. The outlet of the evaporation channel is connected to the inlet of the first vapor-liquid separator via pipe A. The vapor phase outlet of the first vapor-liquid separator is connected to the inlet of the vapor phase evaporation channel via a pipe. The outlet of the vapor phase evaporation channel is connected to the inlet of the second vapor-liquid separator via pipe B. The liquid phase outlet of the first vapor-liquid separator is connected to the inlet of the liquid phase evaporation channel via pipe C. A delivery pump is installed on pipe C.

2. The system according to claim 1, characterized in that: The multi-channel heat exchanger is a plate-fin heat exchanger, preferably. The multi-channel heat exchanger includes baffles, fins, guide vanes, seals, and end caps. Fins and guide vanes are placed between adjacent baffles, and the sides are sealed with seals to form a sandwich structure, creating channels. Preferably, the guide vanes, seals, and end caps separate different heat exchange zones; more preferably, The fins are straight or corrugated; and / or, The distance between two adjacent partitions is 2-10mm.

3. The system according to claim 2, characterized in that: The active pharmaceutical ingredient (API) channel is adjacent to the steam condensate channel and the distillation liquid phase channel, respectively, forming a first heat exchange area. Preferably, the heat exchange area between the steam condensate channel and the API channel is 5%-40% of the API channel, more preferably 10%-30%; and / or, the heat exchange area between the distillation liquid phase channel and the API channel is 20%-60% of the API channel, more preferably 30%-50%; and / or, the adjacent area between the steam condensate channel and the distillation liquid phase channel is 2%-30% of the steam condensate channel, more preferably 5%-15%. The steam channel and the evaporation channel are adjacent to each other, forming a second heat exchange area. Preferably, the heat exchange area between the steam channel and the evaporation channel is 60%-100% of the evaporation channel, more preferably 70%-90%; and / or, The vapor phase evaporation channel is adjacent to both the circulating water channel and the chilled water channel, forming a third heat exchange region. Preferably, the heat exchange area between the circulating water channel and the vapor phase evaporation channel is 20%-60% of the vapor phase evaporation channel, more preferably 30%-50%, and / or, the heat exchange area between the chilled water channel and the vapor phase evaporation channel is 5%-20% of the vapor phase evaporation channel, more preferably 5%-10%, and / or, the circulating water channel and the chilled water channel are not adjacent; further preferably, The first heat exchange region is 20%-60% of the total volume of the multi-channel heat exchanger, preferably 30%-50%, and / or the second heat exchange region is 10%-60% of the total volume of the multi-channel heat exchanger, preferably 20%-50%, and / or the third heat exchange region is 20%-50% of the total volume of the multi-channel heat exchanger, preferably 30%-40%.

4. The system according to claim 3, characterized in that: The multi-channel heat exchanger is a cross-flow plate-fin heat exchanger; and / or... The first heat exchange zone comprises three stacked layers, with the steam condensate channel and the evaporated liquid phase channel optionally positioned in the upper and lower layers of the raw material channel after partial stacking; and / or, The second heat exchange zone comprises two stacked layers, one of which serves as a steam channel and the other as an evaporation channel; and / or, The third heat exchange zone comprises three stacked interlayers, with the circulating water channel and the chilled water channel optionally located in the upper and lower interlayers of the vapor phase evaporation channel.

5. The system according to claim 1, characterized in that: The steam condensate channel is discharged externally; and / or, The inlet of the active pharmaceutical ingredient channel is connected to the source of the active pharmaceutical ingredient via a pipeline; and / or, The outlet of the evaporation liquid phase channel yields a concentrated product; and / or, The inlet of the steam passage is connected to a steam source via a steam inlet pipe, and the steam inlet pipe is equipped with a regulating valve; and / or, A temperature sensor is installed on pipe A; and / or, A temperature sensor is installed on pipe B; and / or, A temperature sensor is installed on pipe C; and / or, The outlet of the circulating water channel is connected to the circulating water return pipe, and the circulating water return pipe is equipped with a regulating valve; and / or, The outlet of the chilled water channel is connected to the chilled water return pipe, and the chilled water return pipe is equipped with a regulating valve.

6. The system according to claim 5, characterized in that: The system is equipped with an automated control unit, which includes a data acquisition module, a data processing module, and a control module connected in sequence. The data acquisition module is electrically connected to the temperature sensors on pipes A and / or B and / or C, respectively. The control module is electrically connected to the regulating valves on the steam inlet pipe and / or the circulating water return pipe and / or the chilled water return pipe, respectively.

7. A concentration method for a drug substance concentration system as described in any one of claims 1-6, characterized in that... The method includes: The active pharmaceutical ingredient (API) enters the API channel of a multi-channel heat exchanger via a pipeline for preheating, then enters the evaporation channel for further heating and evaporation. After vapor-liquid separation in the first vapor-liquid separator, the evaporated liquid phase is pumped into the evaporation liquid phase channel of the multi-channel heat exchanger to recover heat, resulting in a concentrated product that is discharged from the multi-channel heat exchanger. The evaporated vapor phase enters the evaporation vapor phase channel of the multi-channel heat exchanger to recover heat, then enters the second vapor-liquid separator. The vapor phase after vapor-liquid separation is sent to the post-processing section, while the liquid phase is sent to the recycling and reuse section. Preferably,... The active pharmaceutical ingredient is preheated by the evaporating liquid phase and / or steam condensate in the first vapor-liquid separator, and then heated and evaporated by steam; the evaporating vapor phase in the first vapor-liquid separator is cooled by circulating water and / or chilled water.

8. The method according to claim 7, characterized in that: The temperature of the steam in the steam channel is 120-200℃, preferably 130-180℃, and / or the flow rate is 5-40m / s, preferably 10-30m / s; and / or, The condensate temperature in the steam condensate channel is 180-80℃, preferably 160-90℃, and / or the flow rate is 0.2-3m / s, preferably 0.5-1.5m / s; and / or, The temperature of the evaporating vapor phase in the vapor phase channel is 40-130℃, preferably 50-110℃; and / or, the flow rate is 2-10m / s, preferably 4-7m / s; and / or, The temperature of the evaporating liquid phase in the evaporation liquid phase channel is 30-130℃, preferably 40-100℃; and / or, the flow rate is 0.2-3m / s, preferably 0.8-2m / s; and / or, The temperature of the circulating water in the circulating water channel is 20-50℃, preferably 30-40℃, and / or the flow rate is 0.2-3m / s, preferably 0.5-2.5m / s; and / or, The temperature of the chilled water in the chilled water channel is 0-30℃, preferably 5-20℃, and / or the flow rate is 0.2-3m / s, preferably 0.5-2.5m / s; and / or, The temperature of the active pharmaceutical ingredient (API) in the API channel is 10-80℃, preferably 20-70℃, and / or the flow rate is 0.2-3 m / s, preferably 0.8-2 m / s; and / or, The temperature in the evaporation channel is 40-120℃, preferably 50-110℃, and / or the flow rate is 0.5-5m / s, preferably 1-3m / s.

9. The method according to claim 7, characterized in that... The method further includes: The automated control unit collects the temperature from the temperature sensor on pipe A via the data acquisition module. The data processing module compares this temperature with a preset value. If the temperature is lower than the preset value, the control module gradually increases the opening of the regulating valve on the steam inlet pipe until it is fully open; if the temperature is higher than the preset value, the control module gradually decreases the opening of the regulating valve on the steam inlet pipe until it is fully closed. Preferably, The preset value of the temperature sensor on pipe A is 80-100℃; and / or, The opening degree of the regulating valve is adjusted in the same way for both gradually increasing and gradually decreasing, preferably with the opening degree changing by 1-5° for every 1° deviation.

10. The method according to claim 7, characterized in that... The method further includes: The automated control unit collects the temperature from the temperature sensor on pipe B via the data acquisition module. The data processing module compares this temperature with a preset value. If the temperature is higher than the preset value, the control module gradually increases the opening of the regulating valve on the circulating water return pipe until it is fully open. If the temperature is still higher than the preset value after the regulating valve on the circulating water return pipe is fully open, the control module opens the regulating valve on the chilled water return pipe and gradually increases its opening until it is fully open. If the temperature is lower than the preset value, the control module first gradually decreases the opening of the regulating valve on the chilled water return pipe until it is fully closed. If the temperature is still lower than the preset value after the regulating valve on the chilled water return pipe is fully closed, the control module gradually decreases the opening of the regulating valve on the circulating water return pipe until it is fully closed. Preferably, The preset value of the temperature sensor on pipe B is 30-50℃; and / or, The opening degree of the regulating valve on the circulating water return pipe and / or the regulating valve on the chilled water return pipe is adjusted to be the same for both gradually increasing and gradually decreasing, preferably with the opening degree changing by 1-5° for every 1° deviation; more preferably, The automated control unit acquires the temperature from the temperature sensor on pipe C via the data acquisition module, and compares the temperature change difference on pipe C in real time via the data processing module. If the temperature change difference on pipe C is greater than a preset value, the control module sets the preset value of the temperature sensor on pipe B; more preferably, The preset value for the temperature difference on pipe C is 5-10℃; and / or, For every 1°C increase or decrease in temperature of the temperature sensor on pipe C, the preset value of the temperature sensor on pipe B increases or decreases by 0.2-1°C.

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