RU2585632C1 - Automated process plant for making suppository mass - Google Patents

Abstract

FIELD: chemistry.

SUBSTANCE: invention relates to chemical processes and equipment, such as mixing units, and is intended for implementation of process of making suppository mass. Plant for production of suppository mass contains at least one reactor with mixer and water heating, which output is equipped with valve; at least one first mixer-homogeniser suppository base preparation containing water jacket for cooling/heating base connected to thermostat. On bottom side mixer is connected to first pipeline for supply to mixer suppository mass from reactor with pump, second pipeline for outlet of prepared base of first mixer, connected to second mixer-homogeniser. Third mixer-homogeniser is connected by means of third pipeline with second mixer to feed latter with substance of required substance. Fourth mixer-homogeniser is connected to second mixer, wherein fourth mixer by means of fifth pipeline is connected downstream to dosing group, between which and fourth mixer back flow temperature sensor is installed.

EFFECT: high output and quality of required product due to staged approach to processing of mass.

17 cl, 1 dwg

Description

Technical field

The invention relates to chemical processes and equipment, such as mixing plants, and is intended for the implementation of the technological process of manufacturing a suppository mass, including the cleaning process, and can find application in various industries, especially preferably in the pharmaceutical industry.

State of the art

Currently, it is widely known the use of mixers of various types for the preparation of solutions, mixtures, masses, including for pharmaceutical needs. Depending on the application of this or that type of mixer, the necessary process of manufacturing (mixing) the components in them is selected.

The prior art method and mixing installation for the preparation of abrasive masses (see, for example, patent RU 2221632, 01/20/2004), B01F 9/12), which is equipped with a crank mechanism, which is kinematically connected with a vertical rotating blade, and the bowl and the blade is equipped with electric drives with stepless speed control. The abrasive mass is mixed in this unit due to a combination of three movements: rotation of the bowl, rotation of the blade and its reciprocating movement. In addition, the electric motors, which rotate the bowl and the blade, provide the possibility of stepless speed control. Mixed components are loaded through the upper part of the bowl, and the finished mixture is unloaded by turning the bowl on hinges by 120 degrees into a previously prepared container.

The prior art also describes a method of mixing upon receipt of a suppository mass (see, for example, patent RU 2376978, 12/27/2009, A61K 9/02) in a mixer "C50.0 type" Drunk barrel "for 5 minutes with constant stirring, and then powder additives are added to the mass at a temperature of (+26) - (+ 30) ° C. In this case, all components of the suppository mass are heated before mixing.

The disadvantage of this method is the impossibility of such modes to obtain the necessary conditional suppository mass, in particular, the drug with interferon alpha-2b due to the need to select special modes for this drug.

Disclosure of invention

The technical problem to which this invention is directed is the development of such a technological installation in which, through the use of various types of mixers and controlled modes, it becomes possible to more accurately and efficiently carry out the process of preparing the desired product.

The technical problem posed is solved due to the fact that the apparatus for manufacturing a suppository mass according to the invention comprises at least one reactor with a stirrer and water heating for melting the components of the suppository mass, the outlet of which is equipped with an aseptic shutter type valve; at least one mixer-homogenizer for preparing a suppository base, comprising a water jacket for cooling / heating the base, connected to the first thermostat, as well as a coaxial mixer and a turbine with a recirculation loop for emulsification, from the bottom of the mixer using an aseptic piston type valve the first and third pipelines are connected for supplying to the mixer components of the suppository mass from the above reactor with the first transfer pump installed behind it, at least th least one filter and a pneumatically controlled diaphragm valve in an aseptic version; a fourth pipeline for leaving the prepared base from the homogenizer mixer, connected to the first mixer and containing at least two piston type valves, an aseptic adjustable pneumatic diaphragm valve, a first circulation pump, at least one filter, a first metering pump and a first flow meter ; a third reactor, connected by means of the fifth pipeline to the first mixer, to supply the desired substance to the last substance, the fifth pipeline comprising at least one piston type valve in aseptic design, a second metering pump and a second flow meter; a second mixer connected to the first mixer using a sixth pipeline containing a piston type valve in an aseptic design and a second transfer pump, while a second mixer using a seventh pipeline including a piston type valve in an aseptic design and a second circulation pump is connected downstream to the metering a group between which and a second mixer a return temperature sensor is installed.

Preferably, the first, second and third reactors, the homogenizer mixer and the first and second mixers each contain a water jacket for heating / cooling the suppository mass, the third reactor connected to the third thermostat for cooling, the homogenizer mixer connected to the first thermostat for heating / cooling, and the first and second mixers - with a second thermostat for heating.

In another particular embodiment of the invention, the installation comprises a second reactor with a stirrer and water heating for melting the components of the suppository mass, connected by a second pipeline and an adjustable pneumatic diaphragm valve in aseptic design with a third pipeline.

Most preferably, the fourth pipeline is made in two-part.

In a particular embodiment of the invention, the first, second and third pipelines are made of reinforced silicone hose with double braid and additional isolation of the operator from high temperatures in the form of a protective casing.

In another particular embodiment of the invention, the first part of the fourth pipeline is made of AISI 316L stainless steel with a polishing degree of Ra <0.8 μm.

The second part of the fourth pipeline, as well as the fifth, sixth and seventh pipelines are made of a silicone hose of increased strength.

In a particular embodiment of the invention, a diaphragm pump is used as the first transfer pump.

In another particular embodiment of the invention, a cam pump is used as the first circulation pump.

In yet another embodiment of the invention, peristaltic dosing pumps are used as the first and second metering pumps.

In yet another embodiment of the invention, peristaltic pumps are used as the second transfer and second circulation pumps.

It is preferable to use mechanical cleaning filters made of stainless steel with a 0.4 mm mesh.

In another embodiment, stainless steel mechanical filters with 0.2 mm mesh are used as filters.

In another particular embodiment of the invention, a nephelometer is installed in the recirculation loop of the mixer-homogenizer.

The technical result of the claimed invention is to increase the yield and quality of the desired product due to a phased approach to the processing of mass.

Brief Description of the Drawings

The drawing shows a General diagram of a technological installation for the manufacture of suppository mass.

The implementation of the invention

In this section, we will consider the most preferred embodiment of the invention, which, as it is clear to a specialist, in no way limits this invention within the framework of this application.

Installation for the manufacture of suppository mass contains two reactors (melters) 1 and 2, respectively.

Each of the reactors 1, 2 is made with a stirrer and water heating to melt the components of the suppository mass. The outputs of the reactors 1, 2 are equipped, respectively, with valves 3 and 4 in the form of adjustable pneumatic piston (slide) valves in aseptic stainless steel design, with a 2-inch (50 mm) bore and a Viton seal.

The installation also includes a transfer pump 10, diaphragm valves 7, 8, 13 and filters 11, 12.

In addition, the installation comprises a homogenizing mixer 21 for preparing a suppository base, comprising a water jacket for cooling or heating (depending on the desired task) the base, which is connected to the first cooling / heating thermostat 22.

The mixer 21 also contains a coaxial mixer and a turbine 16 for emulsification. From the bottom of the mixer 21, by means of a piston type valve 15, which is made similar to valves 23 and 27, a first pipe 5, 14 is connected for supplying suppository mass from the above reactors 1 or 2 to the mixer 21, as will be shown below, depending from the mass preparation circuit, the process of mass flow into the mixer 21 can occur with the possibility of variable connection of reactors 1 and 2, either simultaneously or one of two.

The first pipeline is made of two parts 5 and 14 and is made of a reinforced silicone hose with a double braid and additional isolation of the operator from high temperatures in the form of a protective casing (not shown in the drawings).

The length of the pipeline 5, 14 is determined by the project, with a 2-inch (50 mm) bore, and is made with thermal insulation to protect the operator from high temperatures - the product's operating temperature is 80 ± 5 ° C.

In the first part 5, the first transfer pump 10 and two mechanical cleaning filters 11, 12 made of stainless steel with 0.4 mm and 0.2 mm cells, respectively, are installed sequentially (in the course of the product from the reactor to the mixer), respectively, further in the course of the product an adjustable pneumatic diaphragm valve 13 is installed in an aseptic stainless steel design with a 2-inch (50 mm) bore.

The mixer-homogenizer 21 will include a nephelometer 17 for determining the optical refractive index of the suppository base, which is connected through the turbine 16 to piston (slide) valves in aseptic stainless steel 18, 19, 20.

The installation comprises a fourth pipeline 26 for outputting the prepared base from the mixer 21, connected to the first mixer 38.

The fourth pipeline 26 is made of two parts.

The first part 26 contains along the flow of the basics the following sequentially installed elements:

- the first valve 23;

- the first circulation pump 24, which is used as a cam pump;

- filter 25 mechanical cleaning of stainless steel with cells of 0.4 mm;

- second valve 27;

- the third valve 28, made similar to the valve 13;

- the first metering pump 30, which is used as a peristaltic metering pump;

- first flow meter 31.

The second part 29 of the fourth pipeline is located after the control valve 28 and connects the first part 26 with the mixer 38 (the possibility of a closed cycle - recirculation loop).

The installation also contains a third reactor 32, connected by means of a fifth pipeline 35, for the possibility of supplying the desired substance to the last substance.

The fifth pipeline includes the following sequentially installed elements along the substance flow:

- the first adjustable pneumatic diaphragm valve 34 in aseptic design;

- the second metering pump 36, made similar to the pump 30;

- second flow meter 37.

The installation comprises a second mixer 41 connected to the first mixer 38 by means of a sixth pipe 48 made in the form of an increased strength silicone hose for pumping a finished suppository mass with a cross-section (internal diameter) 16 mm (product working temperature 33 ± 3 ° C).

The pipeline contains, in the course of the mass flow from the first mixer 38 to the second mixer 41, an aseptic adjustable pneumatic diaphragm valve 39, and a second transfer pump 40, installed in series with the second mixer 41, by means of the seventh pipeline 45, which is similar to the pipeline 48, a metering group 46, between which and a second mixer 41, a return temperature sensor 47 is installed. The pipe 45 includes an adjustable aseptic piston valve 43 and a second circulation pump 44.

In this case, the first 1, second 2 and third 32 reactors, the homogenizer mixer 21 and the first 38 and second 41 mixers each contain a water jacket for heating / cooling the suppository mass, and the third reactor 32 is connected to the third thermostat 33 for cooling, the mixer the homogenizer 21 is connected to the first thermostat 22 for heating / cooling, and the first 38 and second 41 mixers are connected to the second thermostat 42 for heating.

Technological automated installation for the manufacture of suppository mass should be located in a separate production room and has connections to external engineering networks of the building.

The operation of the device is carried out in this way.

At the same time, in the same room, the process of preparing the suppository base of one series in a mixer-homogenizer in one mixer-homogenizer can be carried out. Before starting production of the series, the equipment is being cleaned.

The process automation system should have different access levels and allow programming of several user programs that are saved, viewed and edited in the system memory.

To clean the line, a CIP system with a pump for supplying washing solution and tap water for rinsing, as well as purified water, is used. The main units of equipment are equipped with shower heads for supplying a washing solution / tap water / purified water. The washing solution / tap water / purified water is drained into the sewer using a CIP wash pump.

The operator enters the room and selects a program on the panel in accordance with the data on the manufactured nomenclature of the drug and the volume of the series. Next, the system asks for the readiness of technological equipment and premises: it is necessary to check whether there are any residues from other preparations in the room, check whether the equipment has been cleaned from the previous series, check the correctness and quality of assembly of collapsible units of equipment (pipelines, etc.), check shut-off equipment . If the operator answers positively to the questions, as well as with the corresponding answers of the system components, LINE moves to the next stage of the process - the stage of preparation of the basis. In this case, instructions on the used units of equipment will be displayed (the operating mode of the equipment is selected).

The operator loads the reactors with the base components and turns on the heating. After the process of preparing the components of the suppository base is completed, the control system gives the command to open the valves 3, 7 and / or 4, 8 and the valve on the manifold 13, in accordance with the scheme used. Next, the inclusion of the pump 10, as well as the opening of the valve 15.

Further, the molten components of the suppository base through a pipeline 5, 6 using a pump 10 and through mechanical filters 11 and 12, a valve 13 is successively pumped from each reactor (melter) 1, 2 to a homogenizer 21 for subsequent cooling (crystallization) using thermostat 22 cooling / heating.

After overloading the entire required amount of suppository base on a calibrated level gauge in reactors 1 and 2, the volume of the suppository base is controlled, at the minimum set value for the selected batch volume, and also when the required value is reached in mixer 21, the control system closes the valves on the pipeline 3, 7, 4 , 8 at the outlet of the corresponding reactor, and the pump 10 and valve 13 are turned off.

In this case, the shutdown of the pump 10 and valve 13 occurs after the release of the line from product residues.

Next, the system proceeds to the cooling process of the suppository base (crystallization). Mixing is carried out using a coaxial mixer. Using the temperature control system 22, coolant with the specified parameters is supplied to the jacket and the suppository base is cooled and crystallized. The crystallization process is monitored using a nephelometer 17, with the recirculation loop on the turbine 16 of the homogenizer mixer 21 constantly on.

Upon reaching the appropriate temperature and turbidity values, the control system signals the possibility of moving to the next stage - the stage of introducing fat-soluble components. The introduction of fat-soluble components in the suppository base is made only after the complete crystallization stage of the suppository base. The components are loaded manually with confirmation of this process on the display of the LINES control system (not shown in the drawing).

Fat-soluble components (one or several components, depending on the formulation, for example, alpha-tocopherol acetate and polysorbate-80) are loaded manually through an inspection window with a diameter of 150-200 mm in the top cover of the homogenizer 21.

Next, the operator confirms the end of the loading procedure on the display of the LINES control system, after which the suppository base is mixed automatically in the set time (programmable parameter). At the end of the set time, the system proceeds to the next task of introducing other components. It is possible to find the intermediate product at the stage for a long time (6 or more hours). The time limit is programmable.

After the admissible mixing time has elapsed, the system submits a request for the need to proceed to the next stage - the introduction of powdered components - and asks for confirmation from the operator. Before the transition of the process to the stage of introducing powdered components, the system asks for the readiness of technological equipment: check whether the equipment has been cleaned from the previous series, check the assembly quality of collapsible units of equipment (pipelines, etc.), check the shut-off equipment. At the same time, the control system’s mimic diagram and basic units of equipment are shown on the control system display, including mixers 38, 41 and reactor 32, as well as the assembly sequence of pipelines 26, 29, 35, 48 and 45 with confirmation of the work performed. Next, it is necessary to calibrate the metering pumps 30, 36 and flow meters 31, 37 in purified water. If the operator answers positively to the questions, as well as with the corresponding answers of the components of the control system, LINE proceeds to the next stage of the process - the stage of introducing powdered components.

Powdered components are pre-crushed to the desired degree of grinding. Dosed loading of powdered powdered raw materials takes place manually through a screw feeder from a closed container through a top fitting with a diameter of 100 mm in the top cover of a homogenizer 21 or 38. The turbine is switched on by the operator before the first dose is applied (programmable parameter). After loading powdered raw materials, the operator confirms the end of the loading procedure, mixing is automatic for a predetermined time (programmable parameter). After the mixing time of the powdered raw materials has elapsed, the control system informs with a notification that the suppository base is ready for transfer to the next stage - the stage of preparation of the suppository mass (introducing the interferon alpha-2b substance). Valve 23 and 27 open, and the suppository mass enters the pipeline using pump 24. After the set value (minute or more) has elapsed, and also when there is a signal from the pump that there is a loaded work program with the necessary parameters, valve 28 opens. Upon receipt the signal from the hydrostatic level sensor about the absence of content in the mixer 38, the pump 30 transmits a portion of the suppository base from the pipeline 29 through the flow meter 31. After filling the mixer 38 and confirming the correct dose of soup of the positive base by the flow meter 31, the substance of interferon alpha-2b is dosed from the reactor 32. The interferon substance is introduced into the suppository base in the mixer 38. Upon receipt of the signal of the hydrostatic level sensor in the mixer 38 and upon confirmation of the correct dose of the suppository base by the flow meter using the metering pump 36 s by controlling the dose through the flow meter 37, the substance of interferon alpha-2b from the reactor 32 is dosed into the mixer 38. When the correct dose is confirmed, the finished supposito is mixed mass with a substance of interferon alpha-2b introduced for a set time at a set speed (programmable parameter). The prepared suppository mass is bottled from the pipeline 45 entering it from the mixer 41, by means of the circulation pump 44, the metering group 46 (type SAAS15) and the return temperature sensor 47. A pump 40 and a valve are used to pump the suppository mass from mixer 38 to 41. 39. Overflow of suppository mass is controlled by level sensors.

Upon reaching the set minimum level of the finished suppository mass in the mixer 41, necessary for the stable operation of the circulation loop, the circulation pump 44 is turned on at an increased speed to fill the pipeline 45 and the dispenser of the dosing group 46 (programmable parameters - temperature, speed). Upon completion of filling the recirculation loop, the pump 44 is switched to the operating mode and a signal is received from the hydrostatic level sensor about the complete overflow of the suppository mass from the mixer 38 to the mixer 41 and a message is displayed on the readiness of the system for filling the suppository mass, which is accompanied by a light indication. The filling takes place automatically from pipeline 45. After emptying the mixer 38 when receiving a signal from the hydrostatic level sensor, the pump 30 transfers the next portion of the suppository base from the pipelines 29 through the flow meter 31. After filling the mixer 38 and confirming the correct dose of the suppository base by the flow meter 31, the interferon alpha substance is dosed -2b from reactor 32.

Using a metering pump 36, with a dose control through the flow meter 37, the interferon alpha-2b substance from the reactor 32 is dosed into the mixer 38. When the correct dose is confirmed, the finished suppository mass is mixed with the introduced interferon alpha-2b substance for the set time at the set frequency rotation (programmable parameter). The signal of the beginning of the next overflow cycle from mixer 38 to mixer 41 is the product level in mixer 41, upon reaching the set minimum level necessary for stable operation of the circulation loop, a portion of the finished suppository mass is transferred from mixer 38 to mixer 41 using pump 40.

When the required number of cycles is carried out, depending on the volume of the series and upon receipt of a signal from the flow meter 31, an insufficient level of suppository base is issued, a message is issued indicating the end of work, as well as an audio and light signal. The contents of the mixer 38 and 41 are drained through the respective drain valves (not shown in the drawing).

Emergency situations in the system are signaled by sound and light situations and are accompanied by the conclusion of emergency messages on the control system display. In the event of an emergency, the system asks the operator for confirmation of the possibility of continuing the process.

Cleaning equipment is as follows.

On the display of the control system, the area to be cleaned and the units of equipment (circuit) are selected. Next, the control system displays a request about the readiness of the process equipment for cleaning. At the same time, the display shows the LINE mimic diagram, indicates the circuit that will be cleaned and the basic units of equipment, as well as the assembly sequence with confirmation of the work performed. If the operator answers “yes” to questions, the LINE switches to the “CLEANING” program. To clean the reactors 1,2, disconnect the pipe 14 after the pump 10 and connect to the drain fitting of the CIP sink. Next, on the CIP wash panel, select the desired wash program. The supply of washing solution and rinse water, as well as purified water, occurs automatically according to a previously installed (programmed) algorithm through the scent heads on the lid of reactors 1, 2. The pipeline section 10 with filters 11 and 12 is dismantled and cleaned manually. At the end of the cleaning process, with positive results of the quality control of wash water with a nephelometer, the system signals the end of the cleaning of the site (circuit) and suggests choosing the cleaning of the next circuit. At the same time, the LINE mimic diagram is shown on the display, the circuit to be cleaned, and the basic units of equipment, as well as the assembly sequence with confirmation of the work performed are indicated. To clean the circuit of the mixer-homogenizer 21, a drain hose of the CIP sink is connected to the valve 13 of the pipes 14. The supply of washing solution and rinsing water, as well as purified water, is carried out automatically according to the previously installed (programmed) algorithm through the scent heads on the cover of the mixer 21. Drainage into the sewer takes place using a CIP-washing pump. At the same time, during the cleaning process, the pump 24 is turned on to clean the recirculation loop of the homogenizer 21. At the end of the cleaning process, with positive results of the quality control of the wash water with a nephelometer, the system signals the end of the cleaning of the section (circuit) and suggests that you clean the next circuit. The main pipelines are manually cleaned in the washing room. The faucets 38, 41 and 21 are cleaned through scented heads, and drains into the wastewater sewer through a CIP wash pump.

Thus, as is clear from the above, due to the gradual clearly dosed and controlled at all stages of the process of preparation of suppository mass using the claimed technological installation provides the claimed technical result - improving the yield and quality of the desired product.

Claims (17)

1. Installation for the manufacture of suppository mass, characterized in that it contains at least one reactor with a stirrer and water heating to melt the components of the suppository mass, the output of which is equipped with a gate valve in aseptic design, at least one homogenizing mixer for preparing the suppository base comprising a water jacket for cooling / heating the base associated with the first thermostat, as well as a coaxial mixer and a turbine with a recirculation loop for emulsification, from The first and third pipelines are connected to the bottom of the mixer-homogenizer using an aseptic piston type valve for feeding suppository components from the above reactor with the first transfer pump, at least one filter and one adjustable pneumatic diaphragm valve installed behind it. aseptically, the fourth pipeline for the exit of the prepared base from the mixer-homogenizer, connected to the first mixer and containing at least two piston type valves, an aseptic adjustable pneumatic diaphragm valve, a first circulation pump, at least one filter, a first metering pump and a first flow meter; a third reactor, connected by means of the fifth pipeline to the first mixer, to supply the desired substance to the last substance, the fifth pipeline comprising at least one piston type valve in aseptic design, a second metering pump and a second flow meter; a second mixer connected to the first mixer using a sixth pipeline containing a piston type valve in an aseptic design and a second transfer pump, while a second mixer using a seventh pipeline including a piston type valve in an aseptic design and a second circulation pump is connected downstream to the metering a group between which and a second mixer a return temperature sensor is installed. 2. Installation according to claim 1, characterized in that it comprises a first reactor with a stirrer and water heating for melting the components of the suppository mass, connected by the first pipeline and an adjustable pneumatic diaphragm valve in aseptic design with the third pipeline. 3. Installation according to claim 1, characterized in that the mixer-homogenizer is made with a water jacket, a stirrer and a turbine. 4. Installation according to claim 1, characterized in that the first and second mixers are connected to the second thermostat and contain each water jacket for heating the suppository mass. 5. Installation according to claim 1, characterized in that the third reactor contains a water jacket for cooling the substance associated with the third thermostat. 6. Installation according to claim 1, characterized in that it contains a second reactor with a stirrer and water heating for melting the components of the suppository mass, connected by a second pipeline and an adjustable pneumatic membrane valve in aseptic design with a third pipeline. 7. Installation according to claim 1, characterized in that the fourth pipeline is made integral and consists of two parts. 8. Installation according to claim 2 or 6, characterized in that the first, second and third pipelines are made of reinforced silicone hose with a double braid and additional isolation of the operator from high temperatures in the form of a protective casing. 9. Installation according to claim 1 or 7, characterized in that the first part of the fourth pipeline is made of AISI 316L stainless steel with a polishing degree of Ra <0.8 μm. 10. Installation according to claim 1, characterized in that the second part of the fourth pipeline, as well as the fifth, sixth and seventh pipelines are made of a silicone hose of increased strength. 11. Installation according to claim 1, characterized in that a membrane pump is used as the first transfer pump. 12. Installation according to claim 1, characterized in that the cam pump is used as the first circulation pump. 13. Installation according to claim 1, characterized in that peristaltic dosing pumps are used as the first and second metering pumps. 14. Installation according to claim 1, characterized in that peristaltic pumps are used as the second transfer and second circulation pumps. 15. Installation according to claim 1, characterized in that the filters used mechanical cleaning filters made of stainless steel with a mesh of 0.4 mm 16. Installation according to claim 1, characterized in that the filters used are mechanical cleaning filters made of stainless steel with a 0.2 mm mesh. 17. Installation according to claim 1, characterized in that a nephelometer is installed in the recirculation loop of the mixer-homogenizer.

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