RU2819482C1 - Method of producing purified water and water for injections using membrane method and system for its implementation - Google Patents

Abstract

FIELD: pharmaceutics.

SUBSTANCE: invention relates to production of water for injections. Method of producing purified water and water for injections, comprising two stages. At the first stage: drinking water is treated on hollow fiber ultrafilters, then water is supplied via pipeline to reverse osmosis membrane, and then water is accumulated in accumulation tank. At the second stage: water is directed to the reverse osmosis membrane, then the water is purified on the electrodeionisation modules, and then passing water through a separate ultrafiltration module with an ultrafilter from a ceramic or polysulphone membrane, after which the obtained pharmacopoeial water is supplied to the consumer, and the unused portion of its flow is supplied to the accumulation tank.

EFFECT: high stability and quality of the obtained water from the point of view of microbiological parameters.

9 cl, 3 dwg, 1 tbl

Description

The present invention relates to a system for producing water that meets pharmacopoeial requirements for the category of water for pharmaceutical use, and can be used in the pharmaceutical industry and medicine to produce purified water (hereinafter VO) and water for injection (hereinafter WDI) by membrane methods, including methods of ultrafiltration and reverse osmosis, implemented in one independent installation, and additional units of reverse osmosis and/or electrodeionization, depending on the salt content of the source water, without the use of filters with granular loading and additional containers.

Known methods for obtaining purified water and water for injection involve preliminary purification of drinking water using bulk filters: deferrization, softening and treatment with a carbon filter. After pre-treatment, the water is supplied to one- or two-stage reverse osmosis units for desalination and then supplied to an electrodeonization unit. Final purification involves treating the water using ultrafiltration membranes to remove pyrogens.

There is a known method for producing purified water (patent CN209974491U, published on January 21, 2020), consisting of 4 consecutive sections of water purification, sequentially connected by pipelines through the filtrate: a section for preliminary preparation of source water, a section for intermediate water purification, a section for water purification and a final section. The source water pre-treatment section consists of a mechanical filter, a source water storage tank, a source water supply pump, a mechanical filter, an activated carbon filter, a softening filter, and a fine filter. The intermediate water treatment section consists of a first-stage high-pressure pump, a first-stage reverse osmosis unit, a first-stage filtrate storage tank, a second-stage high-pressure pump, a second-stage reverse osmosis unit, and a filtrate storage tank. The water purification section consists of a demineralized water supply pump, an electrodeionization unit and a storage tank for purified water. The final treatment section consists of a purified water distribution pump, an ultraviolet disinfection installation and a fine filter installed at the purified water distribution point. This method is a classic way to obtain purified water and allows you to obtain purified water that meets pharmacopoeial requirements.

There is a known method for producing water for pharmaceutical purposes (patent CN208907060U; published on May 28, 2019). The pre-filter system consists of a mechanical filter, a carbon filter, a softening filter and a fine filter. Pre-prepared water enters a stainless steel storage tank, followed by post-treatment at a reverse osmosis and electrodeionization unit and collection of purified water in a stainless steel storage tank. Such a system makes it possible to obtain purified water of pharmacopoeial quality, as well as to carry out automatic sanitary treatment of the system from the softened water collection area to the water distribution area to the consumer.

A common disadvantage of the described methods for obtaining purified water is the use of backfill filters in the area of preliminary preparation of source water. Backfill filters have a developed surface that is prone to microbiological contamination and are also difficult to carry out effective sanitary treatment.

There is a known method for producing purified water and water for injection from waters of natural sources, which is carried out by the complex use of filtration, ultrafiltration, reverse osmosis, sorption, ion exchange, and sterilizing processes in a certain sequence, described in patent RU 2258045C1, publ. 08/10/2005. The installation for implementing the method consists of a coarse filter, a pre-filter, a pressure pump, an ultrafiltration module, a high-pressure pump, a reverse osmosis unit, a carbon filter, a sorption filter, an ion exchange filter with cation exchange loading, an ion exchange filter with an anion loading, a filter cartridge for sterilization.

The ultrafiltration module is made of porous fibers, with the help of which purification from high molecular weight organic compounds and suspended colloidal particles with a pore size of 0.01 microns is achieved, with a selectivity of up to 60%. After water treatment at the reverse osmosis stage - an electrical resistivity indicator equal to at least 0.1 MOhm cm (at a temperature of (20.0±1.0)°C); after water treatment at the stages of ion exchange - an indicator of electrical resistivity in the range from 0.5 to 2.5 MOhm m (at a temperature of (20.0 ± 1.0) ° C), which corresponds to a specific electrical conductivity of 0, 4-2.0 µS/cm. The installation allows you to obtain water from natural sources that meets the composition requirements of FS 42-2620-97 “Water for injection”.

The disadvantages of this method and the installation that implements it are:

- the resulting water complies with the requirements of FS 42-2620-97 “Water for Injection”, which are no longer in force;

- the method does not exclude the use of backfill filters, and therefore the risks of microbial contamination remain as high as in other known installations;

- the presence of granular material in the system - ion exchange resin, leading to the need for regular regeneration of the used ion exchange resins, associated with working with acid and alkali. This leads to the formation of chemically aggressive wastewater, which must be neutralized before being discharged into the industrial sewer, which is associated with the need to introduce an additional purification stage, additional equipment, additional energy and labor costs and, as a result, an increase in the cost of production as a whole.

- the pharmacopoeia requires obtaining purified water only from drinking water, therefore, if obtained from natural water, it cannot correspond to the FS.

There is a known method for producing water for injection according to patent CN212451018U; publ. 02.02.2020, according to which the source water is supplied to the tank, where it is mixed with sodium hypochlorite for disinfection. The feed pump is then directed to a mechanical filter to remove suspended solids. Next, the source water is fed to softening filters installed one after the other, and then to an activated carbon filter to adsorb residual organic substances and added sodium hypochlorite. After the filter with activated carbon into the pipeline, which is dosed to adjust the pH of the water. Next, trace amounts of suspended particles, colloidal and other substances larger than 5 microns in size remaining in the water are filtered out using a cartridge filter until complete preliminary purification.

Then the treated water is heated in a plate heat exchanger and fed to a two-stage reverse osmosis unit, after which the permeate is fed to an electrodeionization unit for complete desalination, and then to an ultrafiltration module to remove microorganisms and endotoxins/pyrogens to produce water for injection.

The water obtained in this way is analyzed to determine water quality using an organic carbon analyzer - a TOC sensor.

This method allows you to produce water for injection without using a distiller, which reduces energy consumption and production costs.

The disadvantage of this method is the use of bed filters and the associated risks of microbial contamination.

A known method is a system for producing high-purity water, described in US patent 8734645B2, publ. 05/27/2014.

The highly purified water production system consists of two UV disinfection units with a wavelength from 185 to 254 nm, between which an ultrafiltration and two-stage reverse osmosis device is installed; after each purification stage, a storage tank is provided. After the second UV disinfection installation, the following purification stages are installed: membrane degassing, electrodeionization, ultrafiltration module. All of the specified elements of the system are located in the order listed and are located one after the other along the flow of water.

The water purification system is additionally equipped with a device for continuous injection of sodium hypochlorite solution into the pipeline in front of the ultrafiltration device.

Source water, purified by an ultrafiltration device, is accumulated in a tank from where it is sent to a two-stage reverse osmosis installation; after each stage of reverse osmosis, a storage tank is provided.

The permeate of the second stage of reverse osmosis enters the second UV disinfection unit with high intensity radiation, with a wavelength ranging from about 185 nm to about 254 nm, and the UV light is of high intensity, which provides a dose of water treatment sufficient to destroy everything organic carbon due to the radical decomposition of water, the generation of singlet oxygen, and the further oxidation of residual organic matter by these radicals to carbon dioxide and water. At least 90,000 microwatt-seconds per square centimeter.

The water purification system also additionally includes treatment in a membrane degassing installation, in which carbon dioxide is removed, and then treatment in an electrodeionization installation to remove residual ionized impurities.

The desalted water obtained after passing through the ultrafiltration module is free of endotoxins/pyrogens and meets pharmacopoeial requirements.

This system does not have backfill filters for pre-treatment of water. This high purity water treatment technology minimizes the possibility of bacterial growth by eliminating the need for pre-treatment of the source water and thus without the need for mechanical filtration, carbon filtration and/or water softening steps.

Combining known technologies makes it possible to obtain high-purity water for the pharmaceutical industry - purified water and water for injection.

The disadvantage of the described UV disinfection installation with a wavelength of 185 nm is associated with the high cost of both the installation itself and the need to regularly replace UV lamps during their operation every 8000-9000 hours.

Another disadvantage is the presence of three intermediate tanks, which increase the size of the system as a whole and lead to an increased risk of secondary contamination of water.

The described method, based on the totality of essential features and the achieved result, can be chosen as the closest analogue (prototype) for the method of obtaining VO and VDI and the system for its implementation.

The objective of the claimed invention is to develop a method for producing VO and VDI, allowing to avoid the use of unreliable fill filters in the installation for obtaining VO and VDI while minimizing the risks of secondary microbial contamination and obtaining VO and VDI that meets the requirements of FS.2.2.0019.18 "Water for injection" , and a system implementing the developed method.

The technical result is an increase in the stability and quality of the resulting water, from the point of view of microbiological parameters.

This problem is solved due to the fact that the method for producing purified water and water for injections includes two stages.

Where in the first stage:

- process drinking water using hollow fiber ultrafilters with a rating of 0.01-0.05 microns,

- then the water is supplied through a pipeline to a reverse osmosis membrane with a salt selectivity of at least 99.8%, where the main removal of dissolved salts from the water occurs,

- and then the water is accumulated in a storage tank.

And at the second stage:

- from the storage tank, water is directed through pipelines using a pump to a reverse osmosis membrane, where alkali-bound carbon dioxide is removed to an electrical conductivity of less than 2.0 µS/cm,

- then the water is purified in electrodeionization modules, where the final removal of dissolved salts occurs to a water conductivity value of more than 10.0 MOhm*cm,

- and then pass the water through a separate ultrafiltration module with an ultrafilter made of a ceramic or polysulfone membrane with a cutoff rating equivalent to less than 15 KDa for globular proteins, after which the resulting pharmacopoeial water is sent to the consumer, and the unused part of its flow is sent to a storage tank.

The membranes at the first stage are hardware-designed as a single unit with an expansion tank, which makes it possible to obtain water depleted in nutrients in one pass, the secondary microbial contamination of which is difficult.

A system for obtaining purified water and water for injection is also proposed, including connected pipes:

- coarse filter,

- pressure reducing valve,

- microfilter,

- hollow fiber ultrafilter,

- pressure tank,

- the first high pressure pump,

- reverse osmosis membrane module,

- storage tank,

- second high pressure pump,

- low pressure UV disinfection unit,

- high-pressure pump,

- reverse osmosis installation,

- electrodeionization unit,

- ultrafiltration module,

- and at least one consumption outlet point.

In this case, water not required by consumers at at least one outlet point of consumption is returned through a pipeline to the storage tank.

Also, the concentrate from the reverse osmosis unit, electrodeionization unit and ultrafiltration module is returned through a pipeline to the storage tank.

Also, before the microfilter, a sodium metabisulfite solution is dosed into the water.

In addition, before the microfilter, periodic supply of reagents to the water is provided: 10% hydrochloric acid or 10% sodium hydroxide and 10% sodium hypochlorite solution, for chemical cleaning of the ultrafiltration module.

And in front of the reverse osmosis membrane module, dosing of an inhibitor is provided to prevent sedimentation on the membrane.

Before the high-pressure pump, dosing of an alkali solution of 0.5-10% is provided into the pipeline in an amount sufficient to bind free carbon dioxide 1-30 mg/l.

Purified water from the electrodeionization unit is additionally heated or cooled by a heat exchanger, and then goes to the ultrafiltration module and to the consumer.

Electrical conductivity and temperature sensors are also installed in front of the heat exchanger.

At the outlet of the system after the ultrafiltration module, a flow meter and an electrical conductivity sensor are installed.

The technical result is,

- in the system for obtaining VO and VDI, the process of obtaining VO/VDI is divided into 2 sections (stages). At the first site, non-pharmaceutical quality water is obtained - demineralized water is obtained using equipment designed in accordance with Drinking Water standards, which is accumulated in a container. Pharmaceutical quality water (PQ/WGI) is obtained in the second section of the system, which is designed according to the requirements of aseptic design; this approach allows us to separate design concepts and reduce the cost of the system without losing the quality of operation.

- the installation for producing VO and VDI is a set of installations designed on the basis of membranes of various types: reverse osmosis and ultrafiltration, membrane electrodeionization technology, while the installation does not require additional tanks and backfill filters, which ensures stable high quality of the resulting water, in terms of microbiological parameters.

- VO/VDI is produced continuously, the excess amount is discharged into a single tank, i.e. there is no VO/VDI storage system, thereby reducing the cost of its maintenance and the risks of secondary contamination in the storage system

The claimed method for producing VO and VDI by the membrane method is implemented using a system, the hydraulic block diagram of which is shown in Fig. 1.

Installation includes:

1 - source water supply pump;

2 - coarse filter 90-130 microns;

3 - microfilter 5-50 microns;

4 - ultrafiltration module;

5 - pressure tank;

6 - high pressure pump;

7 - reverse osmosis membrane module;

8 - storage tank for demineralized water;

9 - high pressure pump;

10 – low pressure UV disinfection unit;

11 - high-pressure pump;

12 - reverse osmosis installation;

13 - electrodeionization unit;

14 - heat exchanger;

15 - ultrafiltration module;

16 - pressure reducing valve;

17 - sodium metabisulfite;

18 - reagents for cleaning the ultrafiltration module;

19 - sampling valve;

20 - ball valve;

21 - inhibitor;

22 - breathing filter (microfilter with a rating of 0.2-0.4 microns made of polypropylene or other suitable material);

23 - alkali solution;

24 - electrical conductivity sensor;

25 - temperature sensor;

26 - flow meter;

27 - electrical conductivity sensor;

hygienic tap at the point of consumption;

28 - organic carbon analyzer.

The installation works as follows.

Using a source water supply pump (1), the source drinking water is supplied to a 90-130 micron coarse filter (2) to remove large particles and scale. Next, water, through a pressure reducing valve (16), is supplied to a microfilter (5-50 microns) made of foamed polypropylene (3) and then to the ultrafiltration module (4).

The pipeline in front of the microfilter (3) is provided with dosing of a sodium metabisulfite solution (17) to remove residual active chlorine, which is initially contained in the source drinking water in a concentration of up to 0.7 mg/l, and periodic supply of reagents (18) into the pipeline is also provided ( hydrochloric acid (10%) or sodium hydroxide (10%) and 10% sodium hypochlorite solution, which are necessary for chemical cleaning of the ultrafiltration module)

Direct flushing of the ultrafiltration module is carried out every fifteen minutes, and backflushing of the ultrafiltration module is carried out when the set pressure drop is reached (more than 500-600 mbar). These operations are carried out using a high pressure pump (6)

The water that has been purified on the ultrafiltration module is supplied through a pipeline to a pressure tank (5), designed to provide a supply of water for backwashing the membranes of the ultrafiltration module (4), as well as for chemical cleaning of the ultrafiltration module (4) and the reverse osmosis membrane module (7 ), which are structurally located in the same space. The pressure tank is a composite polymer vessel with a volume equal to three to five volumes of the ultrafiltration membrane module.

The pressure tank (5) is equipped with a mechanical valve for releasing air (air vent), which forces out or fills the pressure tank (5) when filling and emptying with water. Next, from the pressure tank (5) using a high-pressure pump (6), water is supplied to the reverse osmosis membrane module (7) for desalting.

The pipeline in front of the reverse osmosis membrane module (7) is provided with dosing of an inhibitor (21) that prevents sedimentation on the membrane. The inhibitor can be used, for example, MF-ISP at a dose of 3 ml/l or any other similar commercial product.

The resulting permeate from the reverse osmosis membrane module (7) is fed into a storage tank (8) equipped with a breathing filter (22).

The storage tank (8) serves to store partially demineralized water and sanitize the system. It is also the boundary of the system in which drinking water is processed.

From the storage tank (8), using a booster pump (9), partially desalted water is supplied to the UV disinfection unit (10). Next, the water is sent to a reverse osmosis installation (12) using a high-pressure pump (11). Before the pump (11) into the pipeline, dosing of an alkali solution of 0.5-10% (23) is provided in an amount sufficient to bind free carbon dioxide (1-30 mg/l) using a standard injection device; dosing can be carried out both in the flow and directly into the storage tank (8).

The permeate from the reverse osmosis unit (12) is supplied for deep desalting to the electrodeionization unit (13). The concentrate (stream A. Fig. 1) from the reverse osmosis installation (12) and electrodeionization (13) is always returned to the demineralized water tank (8).

The quality and temperature of the resulting purified water at the electrodeionization unit (13) is controlled using an electrical conductivity sensor (24) and a temperature sensor (25);

The resulting purified water at the electrodeionization unit (13) is supplied to the heat exchanger (14) for heating/cooling - maintaining the temperature of the purified water in the range of 70-85 ^o C or less than 25 ^o C, depending on consumer requirements.

Heated/cooled water is supplied to the ultrafiltration module (15) to remove endotoxins/pyrogens (bacterial toxic substances that are structural components of bacteria and are released only when the bacterial cell disintegrates). The concentrate from the ultrafiltration unit (15), stream A (Fig. 1), is returned to the demineralized water container (8). If it is necessary to maintain a temperature range of 70-85 ^o C, the water flow should be cooled to a temperature of no more than 25 ^o C before returning to the container (8).

The resulting demineralized water enters the pipeline on which fittings are placed to organize the consumption of the resulting VO/VDI. Excess unconsumed water is discharged into the demineralized water tank (8).

The flow and quality of VO/VDI are controlled using a flow meter (26) and an electrical conductivity sensor (27) installed on the pipeline after the ultrafiltration module (15).

To determine the quality of the resulting VO/VDI, its electrical conductivity is determined. Electrical conductivity values of more than 5 MOhm/cm at 25 ^o C indicate its quality.

The quality of the resulting demineralized water is also monitored using an organic carbon analyzer (28). Organic carbon content values less than 150 µg/l indicate water quality. Sensors also monitor flow (26) and electrical conductivity (27).

The selection of demineralized water is carried out at the point of consumption using a tap (29).

Provision is made for returning unused VO/VDI to the demineralized water container (8).

The operation of the system is fully automated and carried out using a controller. Operator participation is necessary when sanitizing the system and monitoring operating parameters.

The quality of the obtained water was experimentally tested using an installation designed and manufactured at the plant of JSC NPK MEDIANA-FILTER. The installation includes the elements outlined in (Fig. 1).

The installation is tested for one month using drinking water from artesian wells in Podolsk.

During the entire test period, the drop across the ultrafiltration membranes is in the range of 350-450 mbar.

Backwashes are carried out automatically every 30 minutes.

By the end of the tests, no signs of irreversible membrane contamination were recorded - the pressure drop across the membranes stabilized at 350-450 mbar and no further increase was observed. Irreversible ones are eliminated - chemically. treatment with reagents (acid alkali), reversible restore productivity simply by backwashing

The reverse osmosis installation is operated on drinking source water with an electrical conductivity of 860 µS/cm and a total hardness of 8.5 mmol/l. The efficiency of the reverse osmosis installation is 75% without signs of deposits forming on the membranes.

Table 1 shows summary operating parameters of the Potok-MF installation.

Table 1. Operating parameters of the Potok-MF installation

Options Source water After the ultrafiltration stage After reverse osmosis stage Flow, l/h 1100 1100 800 Hardness, mmol/l 7.5-8.5 7.5-8.5 <0.05 Electrical conductivity, µS/cm 830-910 830-910 28-36 Linear speed through the membrane, l/m ² h - 61 27.6

Photo installations "Potok-MF" are shown in Fig. 2-3

Thus, for the first time, a technology has been developed for producing purified water and water for injection using a membrane method, including ultrafiltration and reverse osmosis methods, and additional reverse osmosis and/or electrodeionization units, depending on the salt content of the source Drinking Water.

The operation of ultrafiltration and reverse osmosis modules was experimentally tested.

The proposed method and system for its implementation ensure the quality of purified water and water for injection that meets the requirements of the Pharmacopoeial Article FS.2.2.0020.15 “Purified Water” and FS.2.2.0020.19 “Water for Injection”.

Claims (33)

1. A method for obtaining purified water and water for injection, including two stages, where in the first stage: - process drinking water using hollow fiber ultrafilters with a rating of 0.01-0.05 microns, - then the water is supplied through a pipeline to a reverse osmosis membrane with a salt selectivity of at least 99.8%, where the main removal of dissolved salts from the water occurs, - and then the water is accumulated in a storage tank, and at the second stage: - from the storage tank, water is sent through pipelines using a pump to a reverse osmosis membrane, where alkali-bound carbon dioxide is removed to an electrical conductivity of less than 2.0 µS/cm, - then the water is purified in electrodeionization modules, where the final removal of dissolved salts occurs to a water conductivity value of more than 10.0 MOhm*cm, - and then pass the water through a separate ultrafiltration module with an ultrafilter made of a ceramic or polysulfone membrane with a cutoff rating equivalent to less than 15 kDa for globular proteins, after which the resulting pharmacopoeial water is sent to the consumer, and the unused part of its flow is sent to a storage tank. 2. The method according to claim 1, characterized in that the membranes at the first stage are hardware designed in the form of a single unit with an expansion tank, making it possible in one pass to obtain water depleted in nutrients, the secondary microbial contamination of which is difficult. 3. System for obtaining purified water and water for injection, including connected by pipes: - coarse filter, - pressure reducing valve, - microfilter, - hollow fiber ultrafilter, - pressure tank, - the first high pressure pump, - reverse osmosis membrane module, - storage capacity, - second high pressure pump, - low pressure UV disinfection unit, - high-pressure pump, - reverse osmosis installation, - electrodeionization unit, - ultrafiltration module, - and at least one consumption outlet point, in this case, before the microfilter, a sodium metabisulfite solution is dosed into the water. 4. The system according to claim 3, characterized in that unclaimed water at at least one outlet point of consumption by the pipeline is returned to the storage tank. 5. The system according to claim 3, characterized in that the concentrate from the reverse osmosis unit, electrodeionization unit and ultrafiltration module is returned through a pipeline to the storage tank. 6. The system according to claim 3, characterized in that in front of the reverse osmosis membrane module there is dosing of an inhibitor that prevents sedimentation on the membrane. 7. The system according to claim 3, characterized in that purified water from the electrodeionization unit is additionally heated or cooled by a heat exchanger, and then supplied to the ultrafiltration module and to the consumer. 8. The system according to claim 7, characterized in that electrical conductivity and temperature sensors are installed in front of the heat exchanger. 9. The system according to claim 3, characterized in that a flow meter and an electrical conductivity sensor are installed at the output of the system after the ultrafiltration module.