JPH01245804A - Removal of solvent contained in solid - Google Patents

Abstract

PURPOSE:To remove a solvent in a solid efficiently within a short period by once dispersing or dissolving a solid contg. the solvent in water and drying the solvent with water. CONSTITUTION:An object to be dried 17 e.g. 20% of ethyl acetate solvent-contg. pharmaceutical material is put in a drying chamber 1 from a feeding port 15 and at the same time warm water heated to a critical acceptable temperature of the object to be dried 17 is introduced into a heating jacket 2 and mixing apparatus 5 from inlets 3 and 9. Then, the object to be dried 17 is mixed by rotation of the mixing apparatus 5 and milling apparatus 13 and predried by decreasing the pressure of the inside of the drying chamber 1 by an evacuating pump 23. Next, once the pressure of the drying chamber is returned to atmospheric pressure, water in a determined amount is supplied from the feeding port 15, and while the water is heated and stirred, the object to be dried is dissolved in the water. Then, the drying chamber 1 is evacuated again, drying is carried out under a prescribed pressure, and most of the solvent with water is evaporated and released from the object to be dried 17.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to a method for drying and removing a solvent contained in a solid.

[Prior art] In the process of drying and removing solvents contained in solids, especially for materials to be dried whose allowable heating temperature is low, drying operations under normal pressure or vacuum are used to reduce the solvent content of the final product to ppn+ order. It can be extremely difficult.

In particular, in fields such as pharmaceuticals that require products with low solvent content, drying is usually carried out over a very long time using a shelf dryer or the like, or after being passed through a pulverizer during the drying process and then dried again. However, the solvent content may not be reduced to the desired value. This is because the solvent trapped between solid molecules is not easily desorbed due to intermolecular bonding, adsorption, etc.

[Problems to be Solved by the Invention] As mentioned above, the solvent trapped between solid molecules often does not reach the desired solvent content even if the material to be dried is pulverized and dried for a long time, resulting in poor quality. Not only was this a management problem, but it was also a factor in increasing costs.

The present invention was made to solve the above problems, and
The objective is to realize a method that can remove solvents contained in solids efficiently in a short period of time.

[Means for Solving the Problems] The present invention is characterized in that after a solid substance containing a solvent is once dispersed or dissolved in water, the solvent is removed by drying together with the water.

[Example] The present invention is a method of dispersing or dissolving a solid substance containing a solvent in water to liberate the solvent trapped between solid molecules, and drying and removing the solvent together with water. An example of a process that can be considered when implementing this is as follows.

Sail 1 Step 1 Reaction ↓ Step 2 Solid-liquid separation ↓ Step 3 Pre-drying ↓ Step 4 Dispersion or dissolution in water ↓ Step 5 Drying Drying example 2 Step 1 Reaction ↓ Step 2 Solid-liquid separation ↓ Step 3 Dispersion in water or dissolution ↓ Step 4 Drying Example 3 Step 1 Reaction ↓ Step 2 Concentration ↓ Step 3 Pre-drying ↓ Step 4 Dispersion or dissolution in water ↓ Step 5 Drying First, in Example 1, the content in the solid after solid-liquid separation When there is a large amount of solvent to be used, this process involves first performing preliminary drying to recover the solvent, then dispersing or dissolving the dried product in water, and drying again to reduce the solvent content to the desired level.

Example 2 is a case where the solvent content in the solid after solid-liquid separation is as low as a few percent (especially when solvent recovery is not a problem), and the solid after solid-liquid separation is directly dispersed or dissolved in N water and then dried. death,
This process lowers the solvent content to the desired level.

Example 3 is a process in which a solution containing a solvent is concentrated and dried, the resulting solid is dispersed or dissolved in water, and the resulting solid is dried again to reduce the solvent content to a desired level.

In the present invention, there are no particular limitations on the equipment used in each of the above processes, and each step in each process may be performed using a single device, or each step may be performed using the same device. . However, in order to avoid complication of each process step, it is desirable to perform each step using the same equipment. For example, in Example 1 above,
Steps 3, 4.5 in Example 2, Steps 2, 3, 4, 5 in Example 3, and possibly Step 1.2
, 3, 4.5 in the same device is preferable.

Furthermore, in the present invention, since heat passes through a highly viscous moisture region during drying, it is generally desirable to use a drying device that has a crushing or dispersing function.

Next, the present invention will be explained in detail using the drawings.

FIG. 1 is a schematic diagram of an example of a drying apparatus for implementing the present invention. In the figure, (1) is a cylindrical drying chamber, and a heating jacket (2) is provided on the peripheral wall and rear wall. Hot water supplied from the inlet (3) passes through the heating jacket (2) and exits. (4).

(5) is a hollow agitator attached to a hollow rotating shaft (6), which is placed inside the drying chamber (1) and rotatably supported by the front and rear side walls via bearings. A pipe (7) is inserted into the hollow part of the rotating shaft (6), and the rotating shaft (8)
Through a rotary joint (not shown) provided at one end, a passage (8) formed by the inner wall of the rotating shaft (8) and the pipe (7) is connected to the hot water inlet (9) and to the pipe (7). ) are each connected to a hot water outlet (10). And the passage (8) of the rotating shaft (6) is connected to the agitator (5) at the rear part.
It is connected to the hollow part (5a) of the stirrer (5), and one end of the pipe (7) is connected to the hollow part (5a) of the stirrer (5) at the front part. (11) is a pulley fixed to the rotating shaft (6),
It is connected to the output shaft of the stirrer drive motor (2) via a belt or the like.

(13) is a crusher that is attached to the stirrer (5) so that it can rotate in forward and reverse directions. Motor (14
) is driven by. (15) is an input port for the material to be dried (17), and (16) is a product discharge port.

(18) is a bag filter whose one end opens into the drying chamber (1), and whose other end is connected to one end of the condenser (19). The other end of the condenser (19) is connected to a liquid receiving tank (22) via a valve, and a vacuum pump (2
3) are connected. (20) and (21) are the inlet and outlet of the cooling water of the condenser (19), and (24) is a pressure gauge.

Next, an embodiment of the present invention using the drying apparatus as described above will be described. In addition, the drying chamber (1) of this drying device
The internal volume is 50g, and the total heat transfer area is 1.0M. The material to be dried (17) contains 20% ethyl acetate, and is pre-dried using this apparatus at a temperature of 50°C and a pressure of 4 to 5 torr for 24 hours to a solvent content of approximately 400 ppm, and then water is added to this. Finish dry and reduce the desired solvent content to 50pp.
n+ closed. That is, first, the drying chamber (
1) The material to be dried containing 20% of the solvent ethyl acetate (1)
7) was charged in an amount of 31.2 kg. Next, set the temperature of the heated hot water to the limit allowable temperature (50°C) of the material to be dried (17),
Hot water is supplied from the inlets (3) and (9) to the heating jacket (2) and the stirrer (5). And the stirrer (5)
The material to be dried (17) is stirred by rotating the crusher (13), and then the pressure inside the drying chamber (1) is lowered to 4 to 5 torr using a vacuum pump (23), and the drying chamber (1) is continuously operated for 24 hours. Pre-dry. Next, once the inside of the drying chamber (1) was returned to atmospheric pressure, 7.5 kg of water was supplied from the inlet (15), and the
Mix and dissolve thoroughly by heating at 50° C. under atmospheric pressure for minutes. Next, vacuum the inside of the drying chamber (1) again for 20 to 30 minutes.
After operating for 2 hours while maintaining the torr, the pressure was reduced to 5 torr.
The temperature was lowered to ~10 tOrr and dried for 10 hours.

In order to track changes in the content of the solvent contained in the material to be dried (17), sampling was performed every hour after the start of drying. The results are shown in FIG.

As is clear from Figure 2, in pre-drying, the material to be dried (1
7) The ethyl acetate in ``H'' remains at 400 ppm, but by adding water to this dried material (17), dispersing and dissolving it well, and drying it again, most of it is removed as the water evaporates. 1 hour after the start of drying, the solvent of
17), after which the solvent content is V 1Op
It remained flat below pi.

Figure 3 shows the results of the same experiment as above using 25 kg of pharmaceutical bulk powder containing 3000 pp11 of ethyl acetate.As in the above case, most of the solvent was converted to water within about 1 hour after the start of drying. withdrew from the group, and then 10pp
It has leveled off around ra.

As is clear from the above example, simply drying the material to be dried (17) takes a long time to remove the solvent contained therein, and once the content decreases to a certain extent, it hardly decreases. By adding water to the material to be dried (17) to disperse or dissolve it well, and then drying it,
It was found that most of the solvent was released together with the water.

The solvent and water removed from the material to be dried (17) as described above are evaporated and removed by the bag filter (■8), and then led to the condenser (19) where they are cooled and turned into liquid. The liquid is collected in the liquid receiving tank (22).

In the above description, the drying apparatus shown in FIG. 1 is used to carry out the present invention, but it goes without saying that drying apparatuses having other structures may also be used. Further, in the above embodiment, a case was shown in which preliminary drying, hydration/dissolution/dispersion, and redrying were performed in the same drying chamber, but each step may be performed in different apparatuses.

Furthermore, the amount of water added in the present invention is not particularly limited, and it goes without saying that the larger the amount, the more effective it is, but from the viewpoint of drying, adding too much water will waste drying energy, so It is desirable to add an appropriate amount of water to reduce the solvent content.

[Effects of the Invention] As is clear from the above description, the present invention is capable of efficiently removing a solvent at a low temperature and in a very short time by adding water to a solid containing a solvent, dissolving or dispersing it, and then drying it. Therefore, it is extremely effective when used to remove solvents from pharmaceuticals and other solid materials that require a reduction in residual solvent.

[Brief explanation of the drawing]

FIG. 1 is a schematic diagram of an example of a drying apparatus for implementing the present invention, and FIGS. 2 and 31 are diagrams showing experimental results of the present invention, respectively. In the figure, (1): Drying chamber, (2): Heating jacket, (5): Stirrer, (6): Rotating shaft, (7): Vibrator, (12): Stirrer drive motor, (13): Crushing. Machine, (14): Drive motor of crusher, (15):
Inlet for drying material, (17): Drying material, (18)
: Bag filter, (19) : Capacitor, (22)
: Receiving tank, (23) : Vacuum pump.

Claims (1)

[Claims] A method for drying and removing a solvent contained in a solid, which comprises dispersing or dissolving a solid containing a solvent in water, and then drying and removing the solvent together with the water. How to remove solvent.