Drying method of aminoglycoside compound

Abstract

The invention relates to an aminoglycoside compound drying method, which adopts a pulse vacuum dryer to dry an aminoglycoside compound material to be dried, and the pulse vacuum dryer comprises a drying box body (1), a vacuum circulating system (2), a pulse system (3), a circulating heating system (4), a cleaning system (5), an automatic control system (6) and a nitrogen charging system (7). The drying method comprises the following steps of (1) a preheating stage, (2) a pulse vacuum drying stage and (3) a cooling stage. The method is suitable for drying solid materials and liquid materials. The method for drying the aminoglycoside compound is simple and convenient to operate, energy-saving, consumption-reducing and suitable for industrial production, and a novel method is provided for drying the aminoglycoside compound.

Description

Technical Field

[0001] The invention relates to the technical field of chemical raw materials, in particular to a drying method and drying equipment for aminoglycoside chemical raw materials. Background Art

[0002] Etimicin sulfate and its intermediates are aminoglycoside compounds, and there are various process requirements in the production process. Since different compounds are subjected to different temperatures, there are also strict requirements for the drying temperature of different compounds. In order to solve the drying problem of Etimicin sulfate and its intermediates, the pharmaceutical industry generally adopts the following drying methods: one is spray drying, but more impurities may be produced during drying due to high temperature; the other is freeze drying, but the drying cycle is long, the energy consumption is high, and the production efficiency is affected. Summary of the invention

[0003] The object of the present invention is to provide a method for drying aminoglycoside compounds.

[0004] The aminoglycoside compounds include azithromycin or its salts, and azithromycin intermediates such as gentamicin C1a, azithromycin sulfate, azithromycin intermediate P1, etc. These compounds need to undergo a drying process during the preparation process, including drying from a liquid or solid state through a dryer to obtain a dry raw material drug product or its intermediate product that is easy to store and has low moisture content.

[0005] The method of the present invention adopts the method designed by the inventor Figure 1 The pulse vacuum dryer shown is used to dry the aminoglycoside compound material.

[0006] The pulse vacuum dryer of the present invention comprises a drying box (1), a vacuum circulation system (2), a pulse system (3), a circulation heating system (4), a cleaning system (5), an automatic control system (6), and a nitrogen filling system (7). These systems are connected to the drying box (1) through different pipelines, and are manually or automatically operated by the automatic control system (6) to ensure that the material in the drying box (1) is dried through the steps of vacuuming, heating, pulse and circulation heating or cooling, ventilation, and nitrogen filling for anti-oxidation.

[0007] The drying box (1) is provided with a plurality of heating plates (8), the heating plates (8) are detachable as a whole, two adjacent heating plates are connected in series via a heat source pipe (9), an inlet (10) is provided below the heat source pipe, and an outlet (11) is provided above the heat source pipe for hot air flow in and out, the outlet being higher than the uppermost partition; the drying box (1) is made into a semi-ellipse at the top and bottom, with arc angle transitions on all sides, the inner shell of the box is provided with a jacket insulation layer, and the drying box (1) is equipped with a front mirror, a side mirror and a mirror light;

[0008] The vacuum circulation system (2) is provided with a vacuum unit, a cooling water tank, a buffer tank, and a stainless steel pipeline, wherein the vacuum unit is composed of a water ring vacuum pump and a Roots vacuum pump;

[0009] The pulse system (3) is provided with a respirator, a pneumatic angle seat valve, a stainless steel pipeline, and a hot air storage tank;

[0010] The circulating heating system (4) is provided with a hot water tank, a hot water pump, and stainless steel pipes, and is heated by hot water;

[0011] The cleaning system (5) is provided with a high-pressure water pump, a pneumatic angle seat valve, a cleaning ball, and a stainless steel pipe;

[0012] The automatic control system (6) is provided with a PLC programmable control and a human-machine interface display. The size and time of the vacuum temperature control in the box are controlled and displayed on a touch screen through a vacuum pressure transmitter and a PLC program. It can be connected to an intelligent control system such as MES and SCADA to realize real-time data collection, remote monitoring, alarm and event management, etc.;

[0013] The nitrogen filling system (7) can be controlled by a valve to select compressed clean air or nitrogen as the gas to be blown out. Nitrogen is used to prevent the material from being oxidized during the drying process or at the end of drying.

[0014] The drying method is carried out through the following steps:

[0015] 1) Preheating stage, the aminoglycoside compound material to be dried is loaded into the drying plate through the feed pipe, and the multi-layer heating plate (8) is started to heat and preheat, the preheating temperature is 55-65° C., and the preheating time is determined according to the properties of the material and is 30 min-60 min;

[0016] 2) Pulse vacuum drying stage: when the aminoglycoside compound material to be dried is a liquid material, a gradient temperature increase method is adopted, and the vacuum pressure gradient decreases, and the required time is determined according to the material concentration; when the aminoglycoside compound material to be dried is a solid, a constant temperature and constant pressure mode or a gradient mode is adopted, or the two modes are used alternately for 2-3 hours; during this stage, the pulse system (3) is turned on to avoid a static vacuum state;

[0017] 3) In the cooling stage, the circulating heating system (4) is turned on to cool down the temperature. During the cooling process, the vacuum circulation system (2) is turned on, and the nitrogen filling system (7) is turned on when the vacuum is released.

[0018] The equipment of the present invention is heated by hot water during operation, and belongs to medium-low temperature (not exceeding 100°C) vacuum drying. The drying method is simple to operate, energy-saving and consumption-reducing, and suitable for industrial production. In order to achieve the above purpose, the present invention provides the following technical solutions:

[0019] The principle of the pulse vacuum drying equipment of the present invention is as follows: the material to be dried is placed in a baking tray, the baking tray is placed on a plate layer for heating, the vacuum system is turned on to evacuate air and dehumidify, so that a vacuum state is formed in the working chamber. Under vacuum conditions, the boiling point of water is reduced, and a large amount of water evaporates. During the drying process, the heated dry hot air (or nitrogen) intermittently enters the box through the pulsating system, quickly takes away the wet air in the box, and achieves a drying effect.

[0020] The drying box is equipped with multiple layers of heating plates, which can be disassembled as a whole. Two adjacent heating plates are connected in series through a heat source pipeline. An inlet is provided below the heat source pipeline, and an outlet is provided above it, which is higher than the top partition. The heating plate solves the problem of uneven heating up and down in vacuum drying. The drying box is made of semi-ellipse at the top and bottom, and has arc angle transitions all around. The inner shell of the box is equipped with a jacket insulation layer, which solves the problem of condensation water on the inner wall of the box and temperature loss of the drying rack in the box, shortening the material drying time. At the same time, the drying box is equipped with a front mirror, side mirrors and mirror lights to facilitate observation of the state of the material in the inner cavity. The pulse vacuum dryer uses hot water for plate layer heating. The hot water heating system consists of a hot water tank, a hot water pump, stainless steel pipes, etc.

[0021] The vacuum system of the pulse vacuum dryer consists of a vacuum unit, a cooling water tank, a buffer tank, stainless steel pipes, etc. The vacuum unit is composed of a water ring vacuum pump and a Roots vacuum pump. The pulse system consists of a respirator, a pneumatic angle seat valve, stainless steel pipes, a hot air storage tank, etc. The air entering the oven is clean air after filtering. Defoaming technology can be selected according to the characteristics of the material during the drying process to avoid material overflow or bubbling. The equipment is equipped with multiple pulse laminar flow ports to form a stable and uniform laminar flow circuit to solve the problem of uneven drying of materials on the upper and lower trays, further ensure uniform drying, and improve drying efficiency.

[0022] The cleaning system of the pulse vacuum dryer includes a high-pressure water pump, a pneumatic angle seat valve, a cleaning ball, a stainless steel pipe, etc. During cleaning, pure water is pressurized by the high-pressure water pump and enters the cleaning ball on the top of the box to high-pressure wash the inside of the box. It automatically shuts down after cleaning is completed.

[0023] The automatic control system of the pulse vacuum dryer is PLC programmable control, with human-machine interface display, and the temperature and time process is instantly printed by a digital printer, which can realize online monitoring and the digital printer can print through a computer.

[0024] The method for drying aminoglycoside compounds using the above dryer is as follows:

[0025] (1) In the preheating stage, the material to be dried is loaded into the drying plate through the feed pipe, and the plate layer is heated for preheating. The preheating temperature is 55-65°C. The preheating time is determined according to the properties of the material and is generally 30 minutes to 60 minutes.

[0026] (2) During the pulse vacuum drying stage, the temperature of the liquid material is increased by a gradient method, and the vacuum pressure decreases by a gradient. The time required is determined according to the material concentration. Solid aminoglycoside compounds can be dried in either a constant temperature and pressure mode or a gradient mode. Generally, the drying effect can be achieved in 2-3 hours. During this stage, the pulse is turned on to avoid a static vacuum state.

[0027] (3) During the cooling stage, the hot and cold water exchange system is turned on for cooling. During the cooling process, the vacuum is turned on, and the nitrogen filling system is turned on when the vacuum is released to prevent oxidation of the material.

[0028] The present invention utilizes the board layer heating and the vacuum pump to evacuate and dehumidify, so as to form a vacuum state in the working chamber and reduce the boiling point of water. During the drying process, the heated dry hot air or nitrogen intermittently enters the box through the pulsation system, quickly taking away the wet air in the box, thereby achieving the drying effect.

[0029] Compared with the prior art, the present invention can effectively dry aminoglycoside compounds, the temperature at each location in the box is uniform, the drying speed is fast, the pollution is small, and energy consumption is saved. The intrinsic quality of the dried items will not be damaged, and the production efficiency is greatly improved under the premise of ensuring the drying efficiency and quality of the products. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] Figure 1 , pulse vacuum dryer structure diagram, in which the components are named as follows: drying box (1), vacuum circulation system (2), pulse system (3), circulation heating system (4), cleaning system (5), automatic control system (6), nitrogen filling system (7), heating plate (8), heat source pipeline (9) inlet (10), outlet (11).

[0031] The drying box (1) is connected to a vacuum circulation system (2), a pulse system (3), a circulation heating system (4), a cleaning system (5), and a nitrogen filling system (7). These systems are all connected to and controlled by an automatic control system (6). The drying box (1) is also provided with a heating plate (8), a heat source pipeline (9), an inlet (10), and an outlet (11). DETAILED DESCRIPTION

[0032] The present invention is further described by the following specific examples, but is not intended to limit the present invention.

[0033] Example 1: Drying of Gentamycin C1a Solution

[0034] 1. Material preparation: Purify and concentrate gentamicin C1a solution, concentration range: 20%-30%, put the liquid into the drying plate using an automatic sampling device, the height range of the liquid in the plate is: 0.8cm-1.2cm;

[0035] 2. Pulse vacuum drying:

[0036] The first stage: preheating stage, the initial temperature is set to 55 ° C, and maintained for 30 minutes to preheat the liquid.

[0037] The second stage: vacuum concentration stage, the temperature is increased in a gradient manner, and the heating is carried out according to the set program. In this stage, the vacuum is turned on, and the vacuum pressure decreases gradually according to the boiling situation of the material until the liquid material becomes a solid state, at which time about 80% of the water has been removed. In order to further reduce the moisture content of the material, the water pump and the Roots pump are operated at the same time, and the vacuum pressure is reduced to the maximum. Because the material belongs to aminoglycosides and has the characteristics of some sugars that are easy to bubble, the pulse function is turned on in this stage to avoid the splashing loss and pollution of the material caused by bubbling, and to avoid static drying. This stage lasts for a period of time until the moisture content of the material drops below 5%.

[0038] The third stage: the cooling stage. To prevent the material from absorbing moisture during the cooling process, the vacuum is kept on until the material drops below 35°C. When the vacuum is turned off, nitrogen is added to the box to collect the material to prevent oxidation of the material.

[0039] Example 2: Drying of Etimicin Sulfate Solution

[0040] 1. Material preparation: After purification and concentration, the decolorized ethimicin sulfate solution is adsorbed on activated carbon, with a concentration range of 30%-40%. The liquid is placed in a drying plate using an automatic sampling device, and the height of the liquid in the plate ranges from 0.8cm to 1.2cm;

[0041] 2. Pulse vacuum drying:

[0042] The first stage: preheating stage, the initial temperature is set to 65 ° C and maintained for 30 minutes to preheat the liquid.

[0043] The second stage: vacuum concentration stage, the temperature is increased in a gradient manner, and the heating is carried out according to the set program. In this stage, the vacuum is turned on, and the vacuum pressure gradient decreases until the liquid material becomes a solid state. At this time, about 80% of the water has been removed. In order to further reduce the crystallization moisture of the material, the water pump and the Roots pump are operated at the same time, the vacuum pressure is reduced to the maximum, and the pulse function is turned on at the same time to avoid static drying. This stage lasts for a period of time until the moisture content of the material drops below 10%.

[0044] The third stage: the cooling stage. To prevent the material from absorbing moisture during the cooling process, the vacuum is kept on until the material drops below 35°C. When the vacuum is turned off, nitrogen is added to the box to collect the material to prevent oxidation of the material.

[0045] Example 3: Intermediate P1 powder

[0046] 1. Preparation of solid materials: Spread the intermediate P1 powder (water content about 10%) evenly on the drying tray;

[0047] 2. Pulse vacuum drying:

[0048] The first stage: preheating stage, the initial temperature is set to 75 ° C and maintained for 10 minutes to preheat the material.

[0049] The second stage: vacuum drying stage, solid material, the temperature is maintained at the set 75 ℃, the vacuum pressure is reduced to the maximum, and the pulse function is turned on at the same time to avoid static drying. This stage lasts about 2-3 hours, and the moisture content of the material can be reduced to below 5%.

[0050] The third stage: the cooling stage. To prevent the material from absorbing moisture during the cooling process, the vacuum is kept on until the material drops below 35°C. When the vacuum is turned off, nitrogen is added to the box to collect the material to prevent oxidation of the material.

Claims

1. A method for drying an aminoglycoside compound, characterized in that: The method uses a pulse vacuum dryer to dry the aminoglycoside compound material to be dried, wherein the pulse vacuum dryer comprises a drying box (1), a vacuum circulation system (2), a pulse system (3), a circulation heating system (4), a cleaning system (5), an automatic control system (6), and a nitrogen filling system (7); The drying box (1) is provided with a plurality of heating plates (8) which can be disassembled as a whole, and two adjacent heating plates are connected in series via a heat source pipe (9). An inlet (10) is provided below the heat source pipe (9), and an outlet (11) is provided above the heat source pipe (9), and the outlet is higher than the uppermost partition. The drying box (1) is semi-elliptical in shape from top to bottom, and has arc angle transitions all around. The inner shell of the box is provided with a jacket insulation layer, and the drying box (1) is equipped with a front mirror, a side mirror, and a mirror light. The vacuum circulation system (2) is provided with a vacuum unit, a cooling water tank, a buffer tank, and a stainless steel pipeline, wherein the vacuum unit is composed of a water ring vacuum pump and a Roots vacuum pump; The pulse system (3) is provided with a respirator, a pneumatic angle seat valve, a stainless steel pipeline, and a hot air storage tank; The circulating heating system (4) is provided with a hot water tank, a hot water pump, and stainless steel pipes, and the heating method is hot water heating; The cleaning system (5) is provided with a high-pressure water pump, a pneumatic angle seat valve, a cleaning ball, and a stainless steel pipe; The automatic control system (6) is equipped with a PLC programmable control, a human-machine interface display, and a temperature and time display digital printer, and can be connected to intelligent control systems such as MES and SCADA to achieve real-time data collection, remote monitoring, alarm and event management, etc.; The nitrogen filling system (7) can be controlled by a valve to select compressed clean air or nitrogen as the gas to be blown out. Nitrogen is used to prevent the material from being oxidized during the drying process or at the end of drying. The drying method is carried out through the following steps: 1) Preheating stage, the aminoglycoside compound material to be dried is placed in a drying tray, and the multi-layer heating plate (8) is started to heat and preheat, the preheating temperature is 55-65° C., and the preheating time is determined according to the properties of the material and is 30 min-60 min; 2) Pulse vacuum drying stage: when the aminoglycoside compound material to be dried is a liquid material, a gradient temperature increase method is adopted, and the vacuum pressure gradient decreases, and the required time is determined according to the material concentration; when the aminoglycoside compound material to be dried is a solid, a constant temperature and constant pressure mode or a gradient mode is adopted, or the two modes are used alternately for 2-3 hours; during this stage, the pulse system (3) is turned on to avoid a static vacuum state; 3) In the cooling stage, the circulating heating system (4) is turned on to cool down the temperature. During the cooling process, the vacuum circulation system (2) is turned on, and the nitrogen filling system (7) can be turned on when the vacuum is released.

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