A drying apparatus for crystallizing a pharmaceutical intermediate and a drying method thereof

Abstract

The application relates to the technical field of drying equipment, in particular to a drying equipment for medicine intermediate crystallization and a drying method thereof. The drying equipment comprises a drying box with a cavity body in the inside, and further comprises a control unit, a feeding port and a drainage port arranged on the drying box, the feeding port and the drainage hole are communicated with the cavity body, a stirring mechanism and a circulating hot air drying mechanism are arranged on the drying box, the stirring mechanism is used for stirring the medicine in the cavity body and disturbing the hot air in the cavity body, the drying equipment for medicine intermediate crystallization and the drying method thereof can be used in the following way: hot air compensation ports are arranged in the front section, the middle section and the rear section in the inside of the shell, and the posture control mechanism is matched, so that the temperature of each part in the inside of the shell can be more conveniently regulated, and the medicine intermediate crystallization in the inside of the shell can be more uniformly dried.

Description

Technical Field

[0001] This invention relates to the field of drying equipment technology, and in particular to a drying equipment and drying method for crystallizing pharmaceutical intermediates. Background Technology

[0002] Drug intermediate crystallization is a crucial step in the synthesis of active pharmaceutical ingredients (APIs), and its drying process directly affects the physicochemical properties of the final product and the stability of the formulation quality. In the current pharmaceutical industry, hot air recirculation drying (HAD) is the mainstream drying process, primarily using forced convection heat transfer to desorb solvent molecules from the crystal surface. However, this technology faces significant technical bottlenecks in practical applications: First, it is difficult to create a uniform temperature field distribution within the drying chamber, and axial and radial temperature gradients often lead to localized overheating or drying blind zones; second, the static heat transfer mode causes an over-drying of the surface crystals and retention of internal moisture, resulting in a "dry surface, wet interior" phenomenon; third, the lack of a precise temperature control compensation mechanism makes it impossible to adjust thermodynamic parameters in real time based on the material's packing morphology.

[0003] More importantly, non-uniform heat transfer in traditional drying processes can lead to the following quality risks: 1. Excessive residual solvent can cause crystal transformation or chemical degradation; 2. Localized overheating can cause the crystal surface to melt and form a dense layer, hindering internal moisture migration; 3. Differences in drying degree between batches can affect the uniformity of subsequent mixing. Although the industry has attempted to introduce alternative solutions such as microwave drying, these generally suffer from technical pain points such as high equipment costs and poor process adaptability. Therefore, developing a dynamic drying system with intelligent temperature control compensation to achieve precise control of the three-dimensional temperature field of the drying chamber has become a key technological breakthrough direction for improving the quality of crystallization drying of pharmaceutical intermediates. Summary of the Invention

[0004] The technical problem to be solved by the present invention is as follows: In order to solve the problems of non-uniform heat transfer in traditional drying processes, such as residual solvent exceeding the standard and causing crystal transformation or chemical degradation, local overheating causing crystal surface melting and forming a dense layer that hinders internal moisture migration, and batch-to-batch drying degree differences affecting the uniformity of subsequent mixing, a drying device and drying method for crystallizing pharmaceutical intermediates are provided.

[0005] The technical solution adopted by the present invention to solve its technical problem is: a drying device for crystallizing pharmaceutical intermediates, including a drying box with an internal cavity, a control unit, a feed inlet and a drain outlet on the drying box, both of which are connected to the cavity, a stirring mechanism and a circulating hot air drying mechanism on the drying box, the stirring mechanism being used to stir the drug in the cavity and to turbulent the hot air in the cavity;

[0006] The circulating hot air drying assembly includes a drying pipe, a booster pump, an air pump, a drying cylinder, and a negative pressure fan. The drying pipe is arranged axially along the drying cylinder and passes through the cavity. One end of the drying pipe is connected to one end of the drying cylinder, and the other end of the drying cylinder is connected to the input end of the air pump. The output end of the air pump is connected to the input end of the booster pump, and the output end of the booster pump is connected to the other end of the drying pipe. The drying pipe is provided with several interconnected hot air compensation ports within the cavity. These hot air compensation ports are axially spaced at intervals in the front, middle, and rear sections of the drying chamber. Each hot air compensation port is equipped with a solenoid valve, and a moisture sensor is provided on one side of each hot air compensation port. The input end of the negative pressure fan is connected to the cavity of the drying chamber, and the output end of the negative pressure fan is connected to one end of the drying cylinder.

[0007] It also includes a posture control mechanism for controlling the posture of the drying chamber. The control unit is connected to the stirring mechanism, booster pump, air pump, negative pressure fan, solenoid valve, moisture sensor, and posture control mechanism. Compared with the prior art, this invention, by providing hot air compensation ports in the front, middle, and rear sections inside the shell, and in conjunction with the posture control mechanism, makes it easier to regulate the temperature at various points inside the shell, thereby enabling more uniform and thorough drying of the drug intermediate crystals inside the shell.

[0008] In some preferred embodiments, the drying tube includes two outer ring pipes and at least two drying branch pipes. The two outer ring pipes are respectively disposed at both ends of the drying branch pipes and connected to each other. The output end of the booster pump is connected to one of the outer ring pipes, and one end of the drying cylinder is connected to the other outer ring pipe. A portion of the drying branch pipe passes through the drying chamber axially and is located in the cavity. Each drying branch pipe is provided with a hot air compensation port.

[0009] In some preferred embodiments, the attitude control mechanism includes a lower base plate, a first cylinder, and a second cylinder. Both the first cylinder and the second cylinder are fixedly mounted on the upper surface of the lower base plate. The extended end of the first cylinder is hinged to one end of the drying chamber, and the extended end of the second cylinder is hinged to the other end of the drying chamber.

[0010] In some preferred embodiments, the drying cylinder includes an outer cylinder body, and a heating tube and a drying plate for drying are disposed inside the outer cylinder body.

[0011] In some preferred embodiments, a plurality of heating tubes are arranged along the circumference of the outer cylinder, a plurality of drying plates are arranged at intervals along the axial direction of the outer cylinder, the heating tubes pass through the drying plates, and a temperature and humidity sensor is arranged inside the outer cylinder.

[0012] In some preferred embodiments, the stirring mechanism includes a drive motor and a spiral stirring blade. The drive motor is fixedly mounted on the drying chamber, and the spiral stirring blade is disposed in the cavity and is connected to the drive motor for transmission.

[0013] In some preferred embodiments, a pressure sensor is provided between the booster pump and the other end of the drying tube, and a one-way valve is provided between one end of the drying tube and the drying cylinder.

[0014] A drying method using a drying device for crystallizing pharmaceutical intermediates as described above, with the following specific operating steps:

[0015] When drying pharmaceutical intermediate crystals, hot air is pumped in direction a through the air outlet of the air pump to the other end of the drying tube and then delivered to one end.

[0016] The user sets the drying time to t, controls the amount of drug intermediate crystals added to the drying chamber at one time and keeps the rotation speed of the stirring mechanism constant, and after the drying process is completed, uses a moisture sensor to detect the dryness of the dried drug intermediate crystals. The detected data is transmitted to the control unit. The control unit sets the minimum acceptable dryness after the drying process to p, the maximum acceptable dryness after the drying process to m, and the dryness detected by the moisture sensor at each location after the drying process is completed to w.

[0017] When the drying time of the drug intermediate crystals in the drying tube reaches t, the moisture sensors located in the front, middle and rear sections of the drying chamber measure the drying index w of the drug intermediate crystals at various points inside. The moisture sensors send the detected data to the control unit, which compares the received drying index w at each point with p and m respectively:

[0018] The monitoring data of the front, middle and rear sections of the drying oven are compared with the preset values ​​in the control unit. If the drying index w in the front, middle and rear sections of the drying oven is within the range of p≤w≤m, then the dryness of the drug intermediate crystals in that section meets the qualified standard. After drying, they can be taken out.

[0019] If any section of the drying oven, including the front, middle, and rear sections, has a case where w < p, then the adjustment continues.

[0020] In some preferred embodiments, if w < p in only one of the front, middle, and rear sections of the drying oven within time t, the following cases apply:

[0021] When the drying index w < p in one section of the front or rear of the drying oven, and the drying indexes of the other two sections are in the range of p ≤ w ≤ m, in this case, regardless of whether the drying index w < p in the front or rear section of the drying oven, the drying index w in the middle section of the drying oven is in the range of p ≤ w ≤ m. The control unit controls the drying index w < p and controls the attitude control mechanism to place the drying oven in an inclined position, so that the drug intermediate crystals at this location move and mix to the other two sections where the drying index is in the range of p ≤ w ≤ m. The drug intermediate crystals at the drying index w < p inside the drying oven are fully mixed with the qualified drug intermediate crystals at the other two locations. Drying continues until the drying index w of the mixed crystals in the front and middle sections or the mixed crystals in the middle and rear sections of the drying oven is dried to the range of p ≤ w ≤ m.

[0022] When the drying index w in the middle section of the drying oven is less than p, and the drying index w in the front and rear sections is within the range of p ≤ w ≤ m, the control unit controls the attitude control mechanism to fully mix the drug intermediate crystals with qualified drying index w in the front and rear sections of the drying oven with the drug intermediate crystals with drying index w < p in the middle section, and continue drying until the drying index w in the front, middle, and rear sections of the drying oven is dried to the range of p ≤ w ≤ m.

[0023] If, within time t, there are two sections (front, middle, and rear) of the drying oven where w < p, then the following situations apply:

[0024] When the drying index w < p in any two sections of the drying oven (front and middle sections, front and rear sections, or middle and rear sections), the control unit controls the attitude control mechanism to fully mix the drug intermediate crystals at the drying index w < p with the drug intermediate crystals at the drying index w within the range of p ≤ w ≤ m. The control unit also controls the corresponding hot air compensation ports at the two locations where the drying index w < p to open, using the hot air compensation ports to compensate for the temperature of the drug intermediate crystals at the drying index w < p, and continues drying. After drying for time t, if the drying index w at all three sections (front, middle, and rear) of the drying oven is within the range of p ≤ w ≤ m, then the drying process is complete.

[0025] In some preferred embodiments, after drying for time t, if the drying index w at the front, middle, and rear sections of the drying chamber is still w < p, the airtightness of the drying chamber needs to be checked. The drug intermediate crystals at the drying index w < p are thoroughly mixed with the drug intermediate crystals at the drying index w within the range of p ≤ w ≤ m. The control unit controls the hot air compensation port at the drying index w < p to open. While keeping other variables constant, the chamber is left to stand for a period of time. Then, the temperature inside the drying chamber is measured using a thermometer. If, after standing for a period of time, the temperature drop index inside the drying chamber is greater than the temperature drop index inside a well-sealed drying chamber for the same period of time, it indicates that there is an air leak in the drying chamber affecting the drying efficiency. At this time, the drying time t is increased until the drying index w at the front, middle, and rear sections of the drying chamber is dried to within the range of p ≤ w ≤ m. After drying is completed, the air leak in the drying chamber is repaired or replaced.

[0026] The beneficial effects of the present invention are as follows: When the drying equipment and drying method for crystallizing pharmaceutical intermediates of the present invention are used, by setting hot air compensation ports in the front, middle and rear sections inside the shell, and in conjunction with the attitude control mechanism, it is easier to control the temperature in various parts of the shell. This makes the crystallization of pharmaceutical intermediates inside the shell more uniform and thorough, avoiding the problems of non-uniform heat transfer in traditional drying processes, such as residual solvent exceeding the standard causing crystal transformation or chemical degradation, local overheating causing crystal surface melting and forming a dense layer that hinders internal moisture migration, and batch-to-batch differences in drying degree affecting the uniformity of subsequent mixing. Attached Figure Description

[0027] The present invention will be further described below with reference to the accompanying drawings and embodiments.

[0028] Figure 1 This is a three-dimensional structural schematic diagram of the present invention;

[0029] Figure 2 This is a schematic diagram of the installation structure between the drying oven 1 and the circulating hot air drying assembly in this invention;

[0030] Figure 3 yes Figure 2 A magnified view of part A in the image;

[0031] Figure 4 yes Figure 2 A magnified view of part B in the image;

[0032] Figure 5 This is a schematic diagram of the structure of the drying cylinder in this invention;

[0033] Figure 6 yes Figure 5 A magnified view of part C;

[0034] Figure 7 This is a schematic diagram of the structure of the present invention during drying.

[0035] In the diagram: 1. Drying chamber; 101. Hollow cavity; 102. Feed inlet; 103. Drain outlet; 2. Drying pipe; 3. Booster pump; 4. Air pump; 5. Drying cylinder; 6. Negative pressure fan; 7. Hot air compensation port; 8. Moisture sensor; 9. Outer ring pipe; 10. Drying branch pipe; 11. Lower base plate; 12. First cylinder; 13. Second cylinder; 14. Outer cylinder; 15. Heating pipe; 16. Drying plate; 17. Temperature and humidity sensor; 18. Drive motor; 19. Spiral agitator; 20. Pressure sensor; 21. One-way valve; 22. Control unit. Detailed Implementation

[0036] The present invention will be further described in detail below with reference to the embodiments:

[0037] This invention is not limited to the specific embodiments listed below. Those skilled in the art can implement this invention using various other specific embodiments based on the content disclosed herein. Any modifications or alterations made to the design structure and concept of this invention fall within the protection scope of this invention. It should be noted that, unless otherwise specified, the embodiments and features described in this invention can be combined with each other.

[0038] In the description of this invention, it should be understood that the terms "center," "longitudinal," "lateral," "upper," "lower," "front," "rear," "left," "right," "vertical," "horizontal," "top," "bottom," "inner," and "outer," etc., indicating orientations or positional relationships based on the orientations or positional relationships shown in the accompanying drawings, are only for the convenience of describing the invention and simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, or be constructed and operated in a specific orientation, and therefore should not be construed as a limitation of the invention. Furthermore, the terms "first," "second," etc., are used for descriptive purposes only and should not be construed as indicating or implying relative importance or implicitly specifying the number of indicated technical features. Thus, a feature defined with "first," "second," etc., may explicitly or implicitly include one or more of that feature. In the description of this invention, unless otherwise stated, "a plurality of" means two or more.

[0039] In the description of this invention, it should be noted that, unless otherwise explicitly specified and limited, the terms "installation," "connection," and "linking" should be interpreted broadly. For example, they can refer to a fixed connection, a detachable connection, or an integral connection; they can refer to a mechanical connection or an electrical connection; they can refer to a direct connection or an indirect connection through an intermediate medium; and they can refer to the internal connection of two components. Those skilled in the art will understand the specific meaning of the above terms in this invention based on the specific circumstances.

[0040] Example 1

[0041] like Figure 1-7 As shown, a drying device for crystallizing pharmaceutical intermediates includes a drying chamber 1, a control unit 22, and a posture control mechanism. The drying chamber 1 has a cavity 101 inside. The drying chamber 1 is provided with a feed inlet 102 and a drain outlet 103. The feed inlet 102 faces upward and is located above one end of the drying chamber 1, and the drain outlet 103 faces downward and is located below the other end of the drying chamber 1. Both the feed inlet 102 and the drain outlet are connected to the cavity 101. The drying chamber 1 is provided with a stirring mechanism and a circulating hot air drying mechanism. The stirring mechanism is used to stir the drug in the cavity 101 and to turbulent the hot air in the cavity 101.

[0042] The circulating hot air drying assembly includes a drying pipe 2, a booster pump 3, an air pump 4, a drying cylinder 5, and a negative pressure fan 6. The drying pipe 2 is arranged axially along the drying cylinder 5 and passes through the cavity 101. One end of the drying pipe 2 is connected to one end of the drying cylinder 5, and the other end of the drying cylinder 5 is connected to the input end of the air pump 4. The output end of the air pump 4 is connected to the input end of the booster pump 3, and the output end of the booster pump 3 is connected to the other end of the drying pipe 2. The drying pipe 2 is provided with several interconnected hot air compensation ports 7 in the cavity 101. The hot air compensation ports 7 are distributed axially at intervals in the front, middle, and rear sections of the drying chamber 1. Each hot air compensation port 7 is provided with a solenoid valve, and a moisture sensor 8 is provided on one side of each hot air compensation port 7. The input end of the negative pressure fan 6 is connected to the cavity 101 of the drying chamber 1, and the output end of the negative pressure fan 6 is connected to one end of the drying cylinder 5.

[0043] The attitude control mechanism is used to control the attitude of the drying chamber 1. The control unit 22 is connected to the stirring mechanism, the booster pump 3, the air pump 4, the negative pressure fan 6, the solenoid valve, the moisture sensor 8 and the attitude control mechanism respectively. By controlling the extension and retraction of the extension ends of the first cylinder 12 and the second cylinder 13, the drying chamber 1 is controlled to be in a horizontal or tilted state.

[0044] The drying tube 2 includes two outer ring tubes 9 and three drying branch tubes 10. The outer ring tubes 9 are annular structures. The two outer ring tubes 9 are respectively set at both ends of the three drying branch tubes 10 and connected to each other. The three drying branch tubes 10 are arranged in parallel to each other. The output end of the booster pump 3 is connected to one of the outer ring tubes 9 on the right. One end of the drying cylinder 5 is connected to the other outer ring tube 9. A part of the drying branch tube 10 passes through the drying box 1 axially and is located in the cavity 101. Each drying branch tube 10 is provided with a hot air compensation port 7.

[0045] The attitude control mechanism includes a lower base plate 11, a first cylinder 12, and a second cylinder 13. Both the first cylinder 12 and the second cylinder 13 are fixedly installed on the upper surface of the lower base plate 11. The extended end of the first cylinder 12 is hinged to the left end of the drying chamber 1, and the extended end of the second cylinder 13 is hinged to the right end of the drying chamber 1. In order to ensure smooth attitude adjustment of the drying chamber 1, a connecting hose is installed between the outer ring pipe 9 on one side of the drying chamber 1 and the booster pump 3. A connecting hose is also installed between the outer ring pipe 9 on the other side of the drying chamber 1 and the one-way valve 21. A connecting hose is also installed between the output end of the negative pressure fan 6 and the drying cylinder 5.

[0046] The drying cylinder 5 includes an outer cylinder 14, inside which heating tubes 15 and drying plates 16 are installed. Several heating tubes 15 are arranged along the circumference of the outer cylinder 14, and several drying plates 16 are spaced apart along the axial direction of the outer cylinder 14. The heating tubes 15 pass through the drying plates 16. A temperature and humidity sensor 17 is installed inside the outer cylinder 14. When the temperature and humidity sensor 17 detects that the internal air temperature of the drying cylinder 5 is lower than the set value in the control unit 22, the temperature and humidity sensor 17 sends the monitoring signal to the control unit 22 wirelessly. The control unit 22 then controls the electric heating tubes 15 to start, thereby heating the internal temperature of the drying cylinder 5 until the internal temperature of the drying cylinder 5 reaches the set value of the control unit 22. Both the drying plates 16 and the electric heating tubes 15 are used to dry and heat the air recovered from inside the drying chamber 1, so that it can be reused.

[0047] The stirring mechanism includes a drive motor 18 and a spiral stirring paddle 19. The drive motor 18 is fixedly installed on the drying box 1. The spiral stirring paddle 19 is disposed in the cavity 101 and is connected to the drive motor 18 for transmission. The interior of the spiral stirring paddle has a cavity for filling a heating medium, which can be hot oil.

[0048] A pressure sensor 20 is provided between the booster pump 3 and the other end of the drying tube 2. A one-way valve 21 is provided between one end of the drying tube 2 and the drying cylinder 5. In this embodiment, the moisture sensor 8 can be an infrared moisture sensor 8, which mainly utilizes the absorption characteristics of infrared light to detect the moisture content by measuring the amount of infrared light absorbed by an object at a specific wavelength. This is existing technology and will not be elaborated on further. The moisture sensor 8 is mainly used to monitor the degree of drying of the drug intermediate crystals.

[0049] The negative pressure fan 6 is used to absorb the water vapor generated by hot air in the drying chamber 1 when drying the drug intermediate crystals and to transport it to the drying cylinder 5. When hot air enters from the drying pipe 2 on the right side of the drying chamber 1 and dries the drug intermediate crystals in the drying chamber 1, a certain amount of water vapor will be generated inside the drying chamber 1. The negative pressure fan 6 is started and will transport the water vapor inside the drying chamber 1 to the drying cylinder 5. The one-way valve 21 is used to prevent the water vapor from flowing back to the drying pipe 2. Then, the negative pressure generated by the air pump 4 will be used to push the absorbed water vapor along the gas flow direction through the drying cylinder 5 and dry and heat it. Finally, the air pump 4 will transport it again for reuse.

[0050] It should be further explained that, in order to maintain a relatively stable efficiency in the drying of drug intermediate crystals inside the drying chamber 1, the control unit 22 integrates a standard pressure value for the pipeline. When the negative pressure fan 6 starts working, the pressure sensor 20 monitors the air pressure inside the drying tube 2. When the air pressure inside the drying tube 2 is lower than the standard pressure value set in the control unit 22, the booster pump 3 is activated. The booster pump 3 increases the pressure inside the pipeline by drawing in, compressing, and discharging gas or liquid, thereby bringing the pressure inside the pipeline up to the set standard pressure value. This prevents the pressure inside the pipeline from decreasing and the gas flow rate from decreasing, which would affect the drying efficiency of the drug intermediate crystals.

[0051] Example 2

[0052] Example 2 is a drying method using the drying equipment described in Example 1. Specifically, it is a drying method using the drying equipment for crystallizing pharmaceutical intermediates as described above, with the following specific operating steps:

[0053] When drying the drug intermediate crystals, hot air is pumped into the drying tube 2 in direction a by the air pump 4, and then into the drying cylinder 5 in direction b. When the hot air enters the drying tube 2, since the two ends of the multiple drying branch tubes 10 are connected to the outer ring tubes 9 on both sides, the hot air inside the outer ring tube 9 continues to be transported to the drying branch tube 10 on the other side in direction c. The heat carried by the hot air inside the drying branch tube 10 is used to dry the drug intermediate crystals.

[0054] The user sets the drying time to t, controls the amount of drug intermediate crystals added to the drying chamber 1 at one time and keeps the rotation speed of the stirring mechanism constant, and after the drying process is completed, the moisture sensor 8 is used to detect the dryness of the dried drug intermediate crystals. The detected data is transmitted to the control unit 22. The control unit 22 sets the minimum acceptable dryness after the drying process to p, the maximum acceptable dryness after the drying process to m, and the dryness detected by the moisture sensor 8 at each location after the drying process is completed to w.

[0055] When the drying time of the drug intermediate crystals in the drying tube 2 reaches t, the moisture sensors 8 located in the front, middle and rear sections of the drying chamber 1 measure the drying index w of the drug intermediate crystals at various points inside. The moisture sensors 8 send the detected data to the control unit 22, and the control unit 22 compares the received drying index w at each point with p and m respectively:

[0056] The monitoring data of the front, middle and rear sections of the drying oven 1 are compared with the preset values ​​in the control unit 22. If the drying index w in the front, middle and rear sections of the drying oven 1 is within the range of p≤w≤m, then the dryness of the drug intermediate crystals in that section meets the qualified standard. After drying, they can be taken out.

[0057] If any section of the drying oven 1, including the front, middle, and rear sections, has a case where w < p, then the adjustment continues.

[0058] Within time t, if only one of the front, middle, and rear sections of drying oven 1 has w < p, then the following cases apply:

[0059] When the drying index w < p in one section of the front or rear of the drying oven 1, and the drying indexes of the other two sections are in the range of p ≤ w ≤ m, in this case, regardless of whether the drying index w < p in the front or rear section of the drying oven 1, the drying index w in the middle section of the drying oven 1 is in the range of p ≤ w ≤ m. The control unit 22 controls the drying index w < p and controls the attitude control mechanism to place the drying oven 1 in an inclined position, so that the drug intermediate crystals at this location move to the other two sections where the drying index is in the range of p ≤ w ≤ m and mix them. The drug intermediate crystals at the drying index w < p inside the drying oven 1 are fully mixed with the qualified drug intermediate crystals at the other two locations, and drying continues until the drying index w of the mixed crystals in the front and middle sections or the mixed crystals in the middle and rear sections of the drying oven 1 is dried to the range of p ≤ w ≤ m.

[0060] When the drying index w of the middle section of drying oven 1 is less than p, and the drying index w of the front and rear sections is within the range of p ≤ w ≤ m, the control unit 22 controls the attitude control mechanism to fully mix the drug intermediate crystals with qualified drying index w in the front and rear sections of drying oven 1 with the drug intermediate crystals with drying index w < p in the middle section, and continue drying until the drying index w of the front, middle and rear sections of drying oven 1 is dried to the range of p ≤ w ≤ m.

[0061] If, within time t, two of the three sections of drying oven 1 (front, middle, and rear) have a state where w < p, then the following situations apply:

[0062] When the drying index w < p in any two sections of the drying oven 1 (front and middle sections, front and rear sections, or middle and rear sections), the control unit 22 controls the attitude control mechanism to fully mix the drug intermediate crystals at the drying index w < p with the drug intermediate crystals at the drying index w within the range of p ≤ w ≤ m. The control unit 22 also controls the corresponding hot air compensation ports 7 at the two drying indexes w < p to open, using the hot air compensation ports 7 to compensate the temperature of the drug intermediate crystals at the drying index w < p, and continues drying. After drying for time t, if the drying index w at the front, middle, and rear sections of the drying oven 1 is all within the range of p ≤ w ≤ m, then the drying process is complete.

[0063] If, after drying for time t, the drying index w at the front, middle, and rear sections of drying chamber 1 still remains w < p, then the airtightness of the drying chamber 1 needs to be checked. The drug intermediate crystals at the drying index w < p should be thoroughly mixed with the drug intermediate crystals at the drying index w within the range p ≤ w ≤ m. Control unit 22 should open the hot air compensation port 7 at the drying index w < p. With other variables remaining constant, allow the chamber to stand for a period of time. Then, use a thermometer to measure the temperature inside the drying chamber 1. If, after standing for a period of time, the temperature drop index inside the drying chamber 1 is greater than the temperature drop index inside a properly sealed drying chamber 1 for the same duration, it indicates that there is an air leak in the drying chamber 1 affecting the drying efficiency. In this case, increase the drying time t until the drying index w at the front, middle, and rear sections of the drying chamber 1 is dried to within the range p ≤ w ≤ m. After drying is complete, repair or replace any leaks in the drying chamber 1.

[0064] The above description, based on the preferred embodiments of the present invention, provides inspiration. Those skilled in the art can make various changes and modifications without departing from the inventive concept. The technical scope of this invention is not limited to the contents of the specification but must be determined according to the claims.

Claims

1. A drying method, characterized in that, The drying method employs a drying device for crystallizing pharmaceutical intermediates. The drying device includes a drying chamber with an internal cavity and a control unit. The drying chamber is provided with a feed inlet and a drain outlet, both of which are connected to the cavity. The drying chamber is provided with a stirring mechanism and a circulating hot air drying mechanism. The stirring mechanism is used to stir the drug inside the cavity and to turbulent the hot air inside the cavity. The circulating hot air drying mechanism includes a drying pipe, a booster pump, an air pump, a drying cylinder, and a negative pressure fan. The drying pipe is arranged axially along the drying chamber and passes through the cavity. One end of the drying pipe is connected to one end of the drying cylinder, and the other end of the drying cylinder is connected to the input end of the air pump. The output end of the air pump is connected to the input end of the booster pump, and the output end of the booster pump is connected to the other end of the drying pipe. The drying pipe is provided with several interconnected hot air compensation ports within the cavity. These hot air compensation ports are axially spaced at intervals in the front, middle, and rear sections of the drying chamber. Each hot air compensation port is equipped with a solenoid valve, and a moisture sensor is provided on one side of each hot air compensation port. The input end of the negative pressure fan is connected to the cavity of the drying chamber, and the output end of the negative pressure fan is connected to one end of the drying cylinder. It also includes an attitude control mechanism, which is used to control the attitude of the drying chamber. The control unit is connected to the stirring mechanism, the booster pump, the air pump, the negative pressure fan, the solenoid valve, the moisture sensor and the attitude control mechanism respectively. The specific operating steps are as follows: When drying pharmaceutical intermediate crystals, hot air is pumped in direction a through the air outlet of the air pump to the other end of the drying tube and then delivered to one end. The user sets the drying time to t, controls the amount of drug intermediate crystals added to the drying chamber at one time and keeps the rotation speed of the stirring mechanism constant, and after the drying process is completed, uses a moisture sensor to detect the dryness of the dried drug intermediate crystals. The detected data is transmitted to the control unit. The control unit sets the minimum acceptable dryness after the drying process to p, the maximum acceptable dryness after the drying process to m, and the dryness detected by the moisture sensor at each location after the drying process is completed to w. When the drying time of the drug intermediate crystals in the drying tube reaches t, the moisture sensors located in the front, middle and rear sections of the drying oven detect the dryness w of the drug intermediate crystals at various points inside. The moisture sensors send the detected data to the control unit, which compares the received dryness w at each point with p and m respectively: The monitoring data of the front, middle and rear sections of the drying oven are compared with the preset values ​​in the control unit. If the dryness w in the front, middle and rear sections of the drying oven is within the range of p≤w≤m, then the dryness of the drug intermediate crystals in that section meets the qualified standard. After drying, they can be taken out. If any segment of the drying oven, including the front, middle, and rear sections, has a w < p condition, the control unit will adjust the attitude control mechanism accordingly.

2. The drying method according to claim 1, characterized in that: The drying tube includes two outer ring pipes and at least two drying branch pipes. The two outer ring pipes are respectively located at both ends of the drying branch pipes and connected to each other. The output end of the booster pump is connected to one of the outer ring pipes. One end of the drying cylinder is connected to the other outer ring pipe. A portion of the drying branch pipe passes through the drying chamber axially and is located in the cavity. Each drying branch pipe is provided with a hot air compensation port.

3. The drying method according to claim 1, characterized in that: The attitude control mechanism includes a lower base plate, a first cylinder, and a second cylinder. Both the first cylinder and the second cylinder are fixedly mounted on the upper surface of the lower base plate. The extended end of the first cylinder is hinged to one end of the drying chamber, and the extended end of the second cylinder is hinged to the other end of the drying chamber.

4. The drying method according to claim 1, characterized in that: The drying cylinder includes an outer cylinder, inside which heating tubes and drying plates for drying are disposed.

5. The drying method according to claim 4, characterized in that: Several heating tubes are arranged along the circumference of the outer cylinder, and several drying plates are arranged at intervals along the axial direction of the outer cylinder. The heating tubes pass through the drying plates, and a temperature and humidity sensor is installed inside the outer cylinder.

6. The drying method according to claim 1, characterized in that: The stirring mechanism includes a drive motor and a spiral stirring blade. The drive motor is fixedly mounted on the drying chamber, and the spiral stirring blade is disposed in the cavity and is connected to the drive motor for transmission.

7. The drying method according to claim 1, characterized in that: A pressure sensor is installed between the booster pump and the other end of the drying tube, and a one-way valve is installed between one end of the drying tube and the drying cylinder.

8. The drying method according to claim 1, characterized in that: If, within time t, there is exactly one section (w < p) among the front, middle, and rear sections of the drying oven, then the following cases apply: When the dryness w < p in one section of the front or rear of the drying oven, and the dryness w in the other two sections is within the range of p ≤ w ≤ m, then regardless of whether the dryness w < p in the front or rear section of the drying oven, the dryness w in the middle section of the drying oven is within the range of p ≤ w ≤ m. The control unit controls the dryness w < p and controls the attitude control mechanism to place the drying oven at an angle, moving the drug intermediate crystals at that location to the other two sections where the dryness w ≤ w ≤ m and mixing them. The drug intermediate crystals at the dryness w < p inside the drying oven are fully mixed with the qualified drug intermediate crystals at the other two locations. Drying continues until the dryness w of the mixed crystals in the front and middle sections or the mixed crystals in the middle and rear sections of the drying oven is dried to the range of p ≤ w ≤ m. When the dryness w of the middle section of the drying oven is less than p, and the dryness w of the front and rear sections is within the range of p ≤ w ≤ m, the control unit controls the attitude control mechanism to fully mix the drug intermediate crystals with the qualified dryness w in the front and rear sections of the drying oven with the drug intermediate crystals with dryness w < p in the middle section, and continue drying until the dryness w of the front, middle and rear sections of the drying oven is dried to the range of p ≤ w ≤ m. If, within time t, there are two sections (front, middle, and rear) of the drying oven where w < p, then the following situations apply: When the dryness w < p in any two sections of the drying oven (front and middle sections, front and rear sections, or middle and rear sections), the control unit controls the attitude control mechanism to fully mix the drug intermediate crystals at the dryness w < p with the drug intermediate crystals at the dryness w within the range of p ≤ w ≤ m. The control unit also controls the corresponding hot air compensation vents at the two dryness w < p locations to open, using the hot air compensation vents to compensate for the temperature of the drug intermediate crystals at the dryness w < p, and continues drying. After drying for time t, if the dryness w in all three sections of the drying oven (front, middle, and rear sections) is within the range of p ≤ w ≤ m, then the drying process is complete.

9. The drying method according to claim 8, characterized in that: If, after drying for time t, the dryness w at the front, middle, and rear sections of the drying oven is still less than p, the airtightness of the drying oven needs to be checked. The drug intermediate crystals at the dryness w < p should be thoroughly mixed with those at the dryness w within the range of p ≤ w ≤ m. The control unit should open the hot air compensation vent at the dryness w < p. With other variables remaining constant, allow the oven to stand for a period of time. Then, measure the temperature inside the drying oven using a thermometer. If, after standing for a period of time, the temperature drop index inside the drying oven is greater than that of a well-sealed drying oven for the same duration, it indicates that there is an air leak affecting the drying efficiency. In this case, increase the drying time t until the dryness w at the front, middle, and rear sections of the drying oven is dried to within the range of p ≤ w ≤ m. After drying is complete, repair or replace any leaks in the drying oven.

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