Preparation method and equipment of vardenafil oral soluble film

Abstract

The invention discloses a vardenafil oral soluble film which is prepared by the following steps: S1, slowly adding methanesulfonic acid phenol into an organic solution at the temperature of-0.5 DEG C to 10 DEG C, and carrying out primary slow stirring and mixing on the solution, S2, adding required raw materials, carrying out mixing work, then waiting for the solution to naturally rise to room temperature, and then waiting for the solution to react for 3-6 hours, so as to obtain the vardenafil oral soluble film. The invention discloses a preparation method of vardenafil, which comprises the following steps of: adding an alkaline stabilizer and a corrigent into vardenafil, adding ice salt water, slowly dropwise adding N-hydroxyethylpiperazine, slowly stirring and mixing, and waiting for reaction, and compared with the prior art, the preparation method has the beneficial effects that the alkaline stabilizer and the corrigent are added in the traditional vardenafil medicament production work, so that the preparation process is simple and convenient, and the cost is low. According to the present invention, the bitter taste and the odor produced during the taking of the vardenafil can be covered, such that the discomfort phenomenon during the taking of the user can be reduced so as to ensure the subsequent sales volume put into the market, and provide the guarantee for the subsequent drug promotion work.

Description

Technical Field

[0001] The invention relates to the field of medical technology, and in particular to a method and equipment for preparing a vardenafil orodispersible film. Background Art

[0002] Vardenafil is used to treat erectile dysfunction. This drug is a type 5 phosphodiesterase (PDE5) inhibitor. Oral administration of this drug can effectively improve the quality and duration of erections and increase the success rate of sexual life in male patients with erectile dysfunction. The initiation and maintenance of penile erection are related to the relaxation of cavernous smooth muscle cells. Cyclic glycoside (cG-P) is a medium that causes relaxation of cavernous smooth muscle cells. Vardenafil is an oral drug for the treatment of erectile dysfunction. When taken orally, it will taste bitter and have a strange smell on the tongue, causing discomfort to the user. For some people who are sensitive to taste, the reaction may be more prominent. These shortcomings will seriously affect the subsequent sales volume put on the market, which will be unfavorable to the promotion of the drug. Summary of the invention

[0003] The object of the present invention is to provide a method and equipment for preparing vardenafil orodispersible film to solve the problems raised in the above background technology.

[0004] To achieve the above object, the present invention provides the following technical solution: a method for preparing a vardenafil orodispersible film, comprising the following steps:

[0005] S1. At a temperature of -0.5°C to 10°C, slowly add methyl sulfonic acid phenol to the organic solution, and initially stir and mix the solution at a slow speed;

[0006] S2, add the required raw materials, mix them, wait for the solution to naturally rise to room temperature, wait for the solution to react for 3-6 hours, then add ice salt water, slowly drop N-hydroxyethylpiperazine, slowly stir and mix, and wait for the reaction;

[0007] S3, adding alkaline stabilizer and flavoring agent, then slowly stirring and mixing, and waiting for reaction;

[0008] S4, then melt and extrude it into a film, and then wait for 0-3 hours for the film to cool and solidify to obtain an orally soluble film.

[0009] Preferably, the flavoring agent in S3 can be honey, sucrose, stevioside, etc.

[0010] Preferably, a preparation device for orodispersible vardenafil film comprises: a mobile car, the top of the mobile car is rotatably connected to a mixing tank, the inside of the mixing tank is rotatably connected to a stirring rod, the bottom of the stirring rod and the bottom of the stirring rod is fixedly connected to a bottom scraper located in the mixing tank, the inner side of the mobile car is fixedly connected to two support blocks, the insides of the two support blocks are rotatably connected to a first rotating rod, the first rotating rod and the top of the stirring rod are both fixedly connected to pulleys, the outer sides of the two pulleys are connected by belt transmission, the bottom of the first rotating rod is fixedly connected to a worm gear, the inner side of the mobile car is fixedly connected to a motor, the output end of the motor is fixedly connected to a first gear, the side of the first gear away from the motor is fixedly connected to a worm, the worm is meshed with the worm gear, the bottom of the first gear is meshed with a second gear, the inside of the second gear is fixedly connected to a second rotating rod, one end of the second rotating rod is fixedly connected to a pinion, the outer side of the mixing tank is fixedly connected to a gear ring, and the pinion is meshed with the gear ring.

[0011] Preferably, a limiting material delivery pipe is fixedly connected to the bottom of the mixing tank, the limiting material delivery pipe is rotatably connected to the moving vehicle, and a solenoid valve is arranged inside the limiting material delivery pipe.

[0012] Preferably, four cylinders are fixedly connected to the bottom of the mobile vehicle, and universal wheels are fixedly connected to the output ends of the four cylinders.

[0013] Preferably, a plurality of first thermal conductive plates are fixedly connected at equal intervals inside the mixing tank, a semiconductor refrigeration plate is fixedly connected to one side of the mixing tank, and a cooling side of the semiconductor refrigeration plate is connected to the first thermal conductive plate.

[0014] Preferably, a plurality of second thermal conductive plates are fixedly connected to the interior of the mixing tank, a heating plate is fixedly connected to one side of the mixing tank, and one side of the heating plate is connected to the second thermal conductive plates.

[0015] Preferably, a plurality of third thermal conductive plates are fixedly connected at equal intervals inside the mixing tank, a temperature sensor is fixedly connected to one side of the mixing tank, and one side of the temperature sensor is connected to the third thermal conductive plates.

[0016] Preferably, a control panel is fixedly connected to one side of the mobile vehicle, and the control panel is electrically connected to the motor, semiconductor refrigeration plate, heating plate, temperature sensor, cylinder and solenoid valve.

[0017] Compared with the prior art, the beneficial effects of the present invention are as follows: by adding alkaline stabilizers and flavoring agents to the traditional vardenafil pharmaceutical production work, the bitterness and peculiar smell produced by the vardenafil during administration can be masked by the added alkaline stabilizer, thereby reducing the discomfort of the user during administration, thereby ensuring the subsequent sales volume put on the market, providing a guarantee for the subsequent drug promotion work, and by the added alkaline stabilizer, the stability of the flavoring agent when mixed with other drugs can be guaranteed when the flavoring agent is added, providing a guarantee for the reaction work. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] For ease of explanation, the present invention is described in detail with reference to the following specific implementations and the accompanying drawings.

[0019] Figure 1 It is a schematic diagram of the overall structure of the present invention;

[0020] Figure 2 It is a structural schematic diagram of the stirring mechanism of the present invention;

[0021] Figure 3 It is a top perspective view of the shunt tube of the present invention.

[0022] In the figure: 1. mobile car; 2. control panel; 3. mixing tank; 4. stirring rod; 5. bottom scraper; 6. pulley; 7. first rotating rod; 8. support block; 9. motor; 10. first gear; 11. worm gear; 12. worm; 13. second gear; 14. second rotating rod; 15. pinion; 16. ring gear; 17. semiconductor cooling plate; 18. heating plate; 19. temperature sensor; 20. cylinder; 21. universal wheel; 22. limit feed pipe; 23. solenoid valve. DETAILED DESCRIPTION

[0023] like Figure 1-3 As shown, this specific implementation adopts the following technical solutions:

[0024] Exemplary embodiments will be described in detail herein, examples of which are shown in the accompanying drawings. When the following description refers to the drawings, the same numbers in different drawings represent the same or similar elements unless otherwise indicated. The embodiments described in the following exemplary embodiments do not represent all embodiments consistent with the present disclosure. Instead, they are merely examples of devices consistent with some aspects of the present disclosure as detailed in the appended claims.

[0025] The technical solutions in the embodiments of the present invention will be described clearly and completely below in conjunction with the accompanying drawings in the embodiments of the present invention. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0026] Embodiment 1:

[0027] The present invention provides a technical solution: a method for preparing a vardenafil orodispersible film, comprising the following steps:

[0028] S1. At a temperature of -0.5°C to 10°C, slowly add methyl sulfonic acid phenol to the organic solution, and initially stir and mix the solution at a slow speed;

[0029] S2, add the required raw materials, mix them, wait for the solution to naturally rise to room temperature, wait for the solution to react for 3-6 hours, then add ice salt water, slowly drop N-hydroxyethylpiperazine, slowly stir and mix, and wait for the reaction;

[0030] S3, adding alkaline stabilizer and flavoring agent, then slowly stirring and mixing, and waiting for reaction;

[0031] S4, then melt and extrude it into a film, and then wait for 0-3 hours for the film to cool and solidify to obtain an orally soluble film.

[0032] The flavoring agent in S3 may be honey, sucrose, stevioside, etc.

[0033] Embodiment 2:

[0034] A preparation device for orally dissolving vardenafil film, comprising: a mobile vehicle 1, the top of the mobile vehicle 1 is rotatably connected to a mixing tank 3, the inside of the mixing tank 3 is rotatably connected to a stirring rod 4, the bottom of the stirring rod 4 and located in the mixing tank 3 is fixedly connected to a bottom scraper 5, the inner side of the mobile vehicle 1 is fixedly connected to two support blocks 8, the insides of the two support blocks 8 are rotatably connected to a first rotating rod 7, the first rotating rod 7 and the top of the stirring rod 4 are both fixedly connected to a pulley 6, the outer sides of the two pulleys 6 are connected by belt transmission, the bottom of the first rotating rod 7 is fixedly connected to a worm gear 11, the inner side of the mobile vehicle 1 is fixedly connected to a motor 9, the output end of the motor 9 is fixedly connected to a first gear 10, the side of the first gear 10 away from the motor 9 is fixedly connected to a worm 12, the worm 12 is meshingly connected to the worm wheel 11, and the bottom of the first gear 10 is meshingly connected to a second gear

[0035] The second gear 13 is fixedly connected to the inside of the second rotating rod 14, one end of the second rotating rod 14 is fixedly connected to the pinion 15, the outer side of the mixing tank 3 is fixedly connected to the ring gear 16, and the pinion 15 is meshed with the ring gear 16;

[0036] By providing the motor 9, the first gear 10, the worm 12, the worm wheel 11, the second gear 13, the second rotating rod 14, the pinion 15, the gear ring 16, the pulley 6, the first rotating rod 7 and the stirring rod 4, the mixing tank 3 and the stirring rod 4 can be rotated in opposite directions at the same time, thereby improving the mixing efficiency and the mixing effect when mixing the solutions, and at the same time, the stirring speed can be adjusted by controlling the rotation rate of the output end of the motor 9 during the mixing work, so that the pharmaceutical solution can be stirred slowly; and by providing the bottom scraper 5, the sediment at the bottom of the mixing tank 3 can be scraped off to prevent sedimentation at the bottom of the mixing tank 3 during the reaction, thereby ensuring the mixing reaction of the drugs.

[0037] Among them, the bottom of the mixing tank 3 is fixedly connected with a limiting material delivery pipe 22, the limiting material delivery pipe 22 is rotatably connected to the mobile vehicle 1, and an electromagnetic valve 23 is arranged inside the limiting material delivery pipe 22, and the discharge of the mixed liquid can be controlled by the electromagnetic valve 23.

[0038] Among them, four cylinders 20 are fixedly connected to the bottom of the mobile vehicle 1, and the output ends of the four cylinders 20 are fixedly connected to universal wheels 21. The universal wheels 21 can be provided to fix the position of the present invention after it is moved to the desired position, and the mixing tank 3 can be raised by the cylinders 20, thereby facilitating the collection of the liquid inside.

[0039] Among them, a plurality of first thermal conductive plates are fixedly connected at equal intervals inside the mixing tank 3, a semiconductor refrigeration plate 17 is fixedly connected to one side of the mixing tank 3, and the cooling side of the semiconductor refrigeration plate 17 is connected to the first thermal conductive plate, which can reduce the temperature of the mixing tank 3 to the required position to ensure the needs of the reaction.

[0040] Among them, a plurality of second thermal conductive plates are fixedly connected inside the mixing tank 3, a heating plate 18 is fixedly connected to one side of the mixing tank 3, and one side of the heating plate 18 is connected to the second thermal conductive plates, which can raise the temperature of the mixing tank 3 to the required position to ensure the needs of the reaction.

[0041] The interior of the mixing tank 3 is fixedly connected with a plurality of third thermal conductive sheets at equal intervals, and one side of the mixing tank 3 is fixedly connected with a temperature sensor 19. One side of the temperature sensor 19 and the third thermal conductive sheet can be connected to the mixing tank 3.

[0042] The temperature in the combination tank 3 is monitored in real time to ensure that the temperature required for the reaction is kept constant.

[0043] Among them, a control panel 2 is fixedly connected to one side of the mobile vehicle 1, and the control panel 2 is electrically connected to the motor 9, the semiconductor refrigeration plate 17, the heating plate 18, the temperature sensor 19, the cylinder 20 and the solenoid valve 23, which can facilitate the control of the overall operation of the present invention and provide convenience for the operation and use of the staff.

[0044] When in use, add the medicine into the mixing tank 3. When mixing is required, the control panel 2 is operated to control the semiconductor refrigeration sheet 17 and the heating plate 18 to adjust the temperature in the mixing tank 3 to the temperature required for the reaction. The temperature sensor 19 can monitor the temperature in the mixing tank 3 in real time. Then the motor 9 is controlled to rotate the first gear 10. The first gear 10 drives the second gear 13 to rotate in the opposite direction. The second gear 13 rotating in the opposite direction drives the pinion 15 to rotate through the second rotating rod 14, so that the pinion 15 drives the internal mixing tank 3 to rotate through the ring gear 16. When the first gear 10 rotates, the worm 12 can drive the first rotating rod 7 through the worm wheel 11. The first rotating rod 7 and the stirring The mixing rod 4 drives the stirring rod 4 and the mixing tank 3 to rotate in the opposite direction through the pulley 6 at the top and the transmission action of the belt. The rotation of the ring gear 16 is driven in the opposite direction by the thread and the pinion 15 set between the worm 12 and the worm wheel 11, and the mixing reaction can be controlled by the rotation speed of the output end of the motor 9. When the stirring rod 4 rotates, the bottom scraper 5 can be driven to scrape the bottom of the inner wall of the mixing tank 3 to prevent the occurrence of sediment. After completing the mixing work, the control cylinder 20 pushes the mobile vehicle 1 to the required height. The position of the mobile vehicle 1 can be fixed and moved through the universal wheel 21. After the mobile vehicle 1 is raised to the required height, the control solenoid valve 23 can be opened to discharge the liquid in the mixing tank 3.

[0045] Although embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that various changes, modifications, substitutions and variations may be made to the embodiments without departing from the principles and spirit of the present invention, and that the scope of the present invention is defined by the appended claims and their equivalents.

[0046] Other embodiments of the present disclosure will be readily apparent to those skilled in the art after considering the specification and practicing the disclosure disclosed herein. This application is intended to cover any variations, uses, or adaptations of the present disclosure that follow the general principles of the present disclosure and include the present disclosure.

[0047] The description and examples are to be regarded as exemplary only, and the true scope of the present disclosure is indicated by the following claims.

Claims

1. A method for preparing a vardenafil orodispersible film, characterized in that: The following steps are involved: S1. At a temperature of -0.5°C to 10°C, slowly add methyl sulfonic acid phenol to the organic solution, and initially stir and mix the solution at a slow speed; S2, add the required raw materials, mix them, wait for the solution to naturally rise to room temperature, wait for the solution to react for 3-6 hours, then add ice salt water, slowly drop N-hydroxyethylpiperazine, slowly stir and mix, and wait for the reaction; S3, adding alkaline stabilizer and flavoring agent, then slowly stirring and mixing, and waiting for reaction; S4, then melt and extrude it into a film, and then wait for 0-3 hours for the film to cool and solidify to obtain an orally soluble film.

2. The method for preparing a vardenafil orodispersible film according to claim 1, characterized in that: The flavoring agent in S3 can be honey, sucrose, stevioside, etc.

3. A preparation device for vardenafil orodispersible film, characterized in that: include: A mobile vehicle (1), wherein the top of the mobile vehicle (1) is rotatably connected to a mixing tank (3), the interior of the mixing tank (3) is rotatably connected to a stirring rod (4), the bottom of the stirring rod (4) and located in the mixing tank (3) is fixedly connected to a bottom scraper (5), the inner side of the mobile vehicle (1) is fixedly connected to two support blocks (8), the interiors of the two support blocks (8) are rotatably connected to a first rotating rod (7), the first rotating rod (7) and the top of the stirring rod (4) are both fixedly connected to a pulley (6), the outer sides of the two pulleys (6) are connected via a belt transmission, the bottom of the first rotating rod (7) is fixedly connected to a worm gear (11), and the mobile vehicle (1) is provided with a plurality of movable wheels. A motor (9) is fixedly connected to the inner side of the motor vehicle (1), and a first gear (10) is fixedly connected to the output end of the motor (9), and a worm (12) is fixedly connected to the side of the first gear (10) away from the motor (9), and the worm (12) is meshingly connected to a worm wheel (11), and a second gear (13) is meshingly connected to the bottom of the first gear (10), and a second rotating rod (14) is fixedly connected to the inside of the second gear (13), and a pinion (15) is fixedly connected to one end of the second rotating rod (14), and a ring gear (16) is fixedly connected to the outer side of the mixing tank (3), and the pinion (15) is meshingly connected to the ring gear (16).

4. The preparation device of a vardenafil orodispersible film according to claim 3, characterized in that: The bottom of the mixing tank (3) is fixedly connected to a limiting material delivery pipe (22), the limiting material delivery pipe (22) is rotatably connected to the moving vehicle (1), and a solenoid valve (23) is provided inside the limiting material delivery pipe (22).

5. The preparation equipment of the vardenafil orodispersible film according to claim 4, characterized in that: Four cylinders (20) are fixedly connected to the bottom of the mobile vehicle (1), and universal wheels (21) are fixedly connected to the output ends of the four cylinders (20).

6. The preparation equipment of the vardenafil orodispersible film according to claim 5, characterized in that: A plurality of first thermal conductive plates are fixedly connected at equal intervals inside the mixing tank (3), a semiconductor refrigeration plate (17) is fixedly connected to one side of the mixing tank (3), and the cooling side of the semiconductor refrigeration plate (17) is connected to the first thermal conductive plate.

7. The preparation device of the vardenafil orodispersible film according to claim 6, characterized in that: A plurality of second thermal conductive plates are fixedly connected inside the mixing tank (3), a heating plate (18) is fixedly connected to one side of the mixing tank (3), and one side of the heating plate (18) is connected to the second thermal conductive plates.

8. The preparation equipment of the vardenafil orodispersible film according to claim 7, characterized in that: A plurality of third thermal conductive plates are fixedly connected at equal intervals inside the mixing tank (3), a temperature sensor (19) is fixedly connected to one side of the mixing tank (3), and one side of the temperature sensor (19) is connected to the third thermal conductive plates.

9. The preparation device of the vardenafil orodispersible film according to claim 8, characterized in that: A control panel (2) is fixedly connected to one side of the mobile vehicle (1), and the control panel (2) is electrically connected to the motor (9), the semiconductor cooling plate (17), the heating plate (18), the temperature sensor (19), the cylinder (20) and the solenoid valve (23).

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