CN106705574A - Solid preparation fabrication equipment and method - Google Patents
Solid preparation fabrication equipment and method Download PDFInfo
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- CN106705574A CN106705574A CN201510790262.7A CN201510790262A CN106705574A CN 106705574 A CN106705574 A CN 106705574A CN 201510790262 A CN201510790262 A CN 201510790262A CN 106705574 A CN106705574 A CN 106705574A
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- Prior art keywords
- pharmaceutical preparation
- solid pharmaceutical
- vacuum
- drying
- container
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- F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
- F26—DRYING
- F26B—DRYING SOLID MATERIALS OR OBJECTS BY REMOVING LIQUID THEREFROM
- F26B5/00—Drying solid materials or objects by processes not involving the application of heat
- F26B5/04—Drying solid materials or objects by processes not involving the application of heat by evaporation or sublimation of moisture under reduced pressure, e.g. in a vacuum
- F26B5/06—Drying solid materials or objects by processes not involving the application of heat by evaporation or sublimation of moisture under reduced pressure, e.g. in a vacuum the process involving freezing
Abstract
The invention provides solid preparation fabrication equipment and method. The solid preparation fabrication equipment is characterized by comprising a spray freeze-drying device and a solid preparation forming device. The solid preparation fabrication method includes the steps that a solution, mixed suspension liquid or emulsion containing medicine effective ingredients is prepared, spray freezing and drying are performed through the spray freeze-drying device under the stirring or non-stirring state, particles obtained through spray freezing and drying are directly fabricated into a solid preparation through the solid preparation forming device, or the particles obtained through spray freezing and drying are mixed with at least one accessory and then fabricated into the solid preparation through the solid preparation forming device. The solid preparation fabrication equipment and method are particularly suitable for but not limited to the production or research process of materials of properties of sensitization, low content proportion, biological activity, heat sensitivity and the like.
Description
Technical field
The present invention relates to a kind of solid pharmaceutical preparation manufacturing equipment and method.
Background technology
Generally, in the production/R＆D process of tablet or capsule it is general have granulation, whole grain, drying,
The pretreatment process such as mixing, the process haves the shortcomings that its is intrinsic, such as take, mix it is uneven, to thermal sensitivity
Material influences larger, easy dust from flying etc..For the pre-treatment with allergenic substance, in addition it is also necessary to consider each
The factors such as seal, the clanability of link, by the extra input for increasing cost.
Method of granulating conventional at present has various, including bulk drug of pretreatment adds with interior granulation, fluidized bed granulation, dry granulation,
Spray-drying process etc., but various methods (in addition to dry granulation) are required to the link by heating, to temperature-sensitive
Property material there is large effect, and easily there are the phenomenons such as glutinous wall in spray drying, on certain office
It is sex-limited.Although dry granulation is without heating link, it also can local heat production in extrusion process, thereby increases and it is possible to produce
The phenomenons such as transformation of crystal, can not completely exclude the influence to heat-sensitive substance.
It is general to be solved by the way of the operation such as crushing after frozen drying again for heat-sensitive substance,
Processing mode such as royal jelly in the A of Patent No. CN 102302108 is to take the method, but the technical process
Need longer time (general 15~24h even longer), the product of gained is generally required after crushing again etc.
It is continuous to operate to complete, operate cumbersome.
Uniformity of dosage units is one of the index directly perceived for investigating mixed effect quality, either traditional granulation-compressing tablet/
Capsule charge technique or direct powder compression/capsule charge technique, there is mixed process.In mixed process,
Because of characteristics such as the intrinsic not good enough, hydrophobic differences of density unevenness one, mobility of solid material, prevent it from as liquid
Body dispersion is equally easy to mix, small or with particularity such as viscosity, hygroscopicity especially for content
The material of matter, mixing just seems more difficult.Therefore, for the mixed process of solid pharmaceutical preparation, uniformity of dosage units
Seem and be even more important.Further, the easy dust from flying of mixed process, is the main original for causing environment and personnel's harm
Therefore one.
The content of the invention
The purpose of the present invention be directed to current tablet, capsule pretreatment process it is comparatively laborious, to heat-sensitive substance
In the presence of defects such as influence, normal freeze-drying time consumption and energy consumptions, a kind of production efficiency is developed high and suitable for temperature-sensitive
The solid pharmaceutical preparation manufacturing equipment and method of property material.
In order to achieve the above object, the invention provides a kind of solid pharmaceutical preparation manufacturing equipment, it is characterised in that bag
Include spraying freeze-drying apparatus and solid pharmaceutical preparation shaped device.
Preferably, described solid pharmaceutical preparation manufacturing equipment also includes mixing arrangement.
Preferably, described solid pharmaceutical preparation manufacturing equipment does not include mixing arrangement.
Preferably, described solid pharmaceutical preparation shaped device is tablet press machine or capsule filler.
Preferably, described spraying freeze-drying apparatus are batch vacuum spraying freeze drying plant or continuous vacuum
Atomizing freeze drying device.
It is highly preferred that described batch vacuum spraying freeze drying plant includes：For being freezed in vacuum spraying
The closed container of material is accommodated in drying process；For liquid atomization to be freezed to be separated into drop and spray into institute
Atomizer in the container stated；Make for forming vacuum environment in a reservoir in vacuum spraying freezing pelletization stage
Constituent part vaporization in described drop is absorbed heat and then drop is lowered the temperature and freezes to form particle, and in drying stage
Maintain the vacuum system of described vacuum environment；And for freezing to avoid in vacuum spraying freezing pelletization stage
Constituent part thawing in described particle and the liter of the constituent part in the particle that drying stage provides described
The temperature adjustment chuck of magnificent heat.
Further, the constituent part in described drop is water, and the constituent part in described particle is ice.
Further, described vacuum spraying freeze drying equipment also includes being used in vacuum spraying freezing granulation rank
Section described in by the constituent part condensation of the drop described in after vaporization and/or after drying stage is by distillation
The condensing unit of the constituent part condensation in grain；It is provided with described container in vacuum spraying freezing granulation rank
Section rotates to avoid the described particle agglomeration for freezing to be formed blocking, and is rotated in drying stage and make described
The inwall of grain rolling and described container up and down exchanges heat and makes sublimation gases stirring from the gap effusion between particle
Oar is mixed, described agitating paddle is located at the bottom of container.
Further, described agitating paddle passes through connecting shaft and motor connection.
Further, described condensing unit is one kind or its combination freezed in chuck and condenser, described
Refrigeration chuck located at the outside of described upper vessel portion, the inside of the chuck that freezes is connected with refrigerant, described condensation
Device is connected outside described container with described container.
Further, described vacuum system includes vavuum pump, and described container is provided with connector；When described
Condensing unit for refrigeration chuck when, described vavuum pump by pipeline connect described in container connector, institute
The pipeline stated is provided with valve；When the combination that described condensing unit is condenser or refrigeration chuck and condenser
When, described condenser connects the connector of described container by pipeline, and described vavuum pump passes through another pipe
Road connects condenser, and the pipeline between described condenser and the connector of described container is provided with valve.
Further, the connector of described container is provided with screen pack.
Further, described refrigeration chuck has refrigerant inlet and a refrigerant exit, described refrigerant inlet and
Refrigerant exit connects the two ends of medium circulation pipeline respectively, and described medium circulation pipeline is provided with fluid pump and use
In the heat exchanger lowered the temperature to refrigerant；Temperature adjustable fluid, described temperature adjustment folder are connected with described temperature adjustment chuck
There is set temperature adjustable fluid entrance and temperature adjustable fluid to export, and described temperature adjustable fluid entrance and temperature adjustable fluid outlet are distinguished
The two ends of temperature adjustable fluid circulation line are connected, described temperature adjustable fluid circulation line is provided with fluid pump and for adjusting
Save the heat exchanger and heater of temperature adjustable fluid temperature.
Further, described heat exchanger connection refrigeration system.
Further, described refrigeration system is compressor.
Further, the rectangular cross-section of described refrigeration chuck, is enclosed with the top one for surrounding described container
Form set；Or, the section of described refrigeration chuck is semicircle, spirally around described container
The some circles in top form set, the refrigerant in described refrigeration chuck can be silicone oil.
Further, the rectangular cross-section of described temperature adjustment chuck, is enclosed with the bottom one for surrounding the container
Form is set；Or, the section of described temperature adjustment chuck is semicircle, spirally under the container
The form of some circles in portion is set, and the temperature adjustable fluid in described temperature adjustment chuck can be silicone oil.
Further, described drop in container not with refrigerant directly contact.
Further, described container is closed container, and top is tubular, and bottom is taper.
Further, described atomizer connects closed liquid distribution pipe road, and described liquid distribution pipe road is provided with pipe
Road flow control valve.
Further, the bottom of described container is provided with the outlet valve for discharging dried material, described discharging
Valve can be connected with material collecting device.
Further, at least one is provided with the outside of the roof and upper portion side wall of described container for shaking off material
Vibrator.
Further, described vibrator drives vibration or motor to drive vibration by gas piston.
Further, the vacuum spraying freeze drying equipment also includes introducing clean water to enter in described container
Row cleaning, and disinfectant is introduced the washing and sterilizing system sterilized in described container, the disinfectant can
Being aseptic pure steam.
Further, described vacuum spraying freeze drying equipment also includes being used for vacuum spraying freeze-drying
The control system of Cheng Jinhang procedure auto-controls, described control system includes programmable logic controller (PLC) (PLC)
At least one of with computer (PC).
It is highly preferred that described continuous vacuum atomizing freeze drying device includes interconnecting composition closed container
Vacuum spraying freezing prilling granulator and dynamic heat drying device；Described vacuum spraying freezing prilling granulator bag
Cannon spray head is included, the atomizer for liquid to be freezed atomization to be separated into drop, institute are provided with the cannon spray head
Stating cannon spray head and being connected to form vacuum environment in closed container makes the constituent part in described drop at this
Heat absorption is vaporized in vacuum environment and then drop is lowered the temperature and freeze to form the vacuum system of ice particle.
Further, the constituent part in the drop is water.
Further, the drop in closed container not with refrigerant directly contact.
Further, the cannon spray head is a part for closed container, and top is tubular, and bottom is taper.
Further, the atomizer connects closed liquid distribution pipe road, and the liquid distribution pipe road is provided with flow tune
Regulating device.
Further, in the drop after the vacuum spraying freezing prilling granulator is also including being used for vaporization
The condensing unit of constituent part condensation.
Further, the condensing unit is the one kind in the first refrigeration chuck and condenser or its combination, institute
The the first refrigeration chuck stated is connected with refrigerant inside the outside on the cannon spray head top, the first refrigeration chuck；Institute
Condenser is stated outside described cannon spray head, and is connected with the cannon spray head.
Further, the vacuum system includes vavuum pump, and described cannon spray head is provided with connector, on connector
It is provided with valve；When described condensing unit is the first refrigeration chuck, vavuum pump connects cannon spray head by pipeline
Connector；When the combination that described condensing unit is condenser or the first refrigeration chuck and condenser, condenser
The connector of cannon spray head is connected by pipeline, vavuum pump connects condenser by another pipeline.
Further, the connector of the cannon spray head is provided with screen pack.
Further, the refrigerant in the first refrigeration chuck is formed by the fluid pump on pipeline and circulates and lead to
Over-heat-exchanger is lowered the temperature.
Further, the rectangular cross-section of the first refrigeration chuck, to surround the top one of the cannon spray head
The form of circle is set；Or, the section of the first refrigeration chuck is semicircle, spirally around the spray
The form of some circles in top of mist cylinder is set, and the refrigerant in the first described refrigeration chuck can be silicone oil.
Further, described refrigerant temperature is -40 DEG C~-100 DEG C.
Further, the lower taper outside of the cannon spray head is provided with the second refrigeration for avoiding ice particle from melting
Chuck, refrigerant is connected with the second refrigeration chuck.
Further, the refrigerant in the second refrigeration chuck is formed by the fluid pump on pipeline and circulates and lead to
Over-heat-exchanger is lowered the temperature.
Further, the rectangular cross-section of the second refrigeration chuck, in the form of being enclosed around tapered outer side one
Set；Or, the section of the second described refrigeration chuck is semicircle, spirally some around tapered outer side
The form of circle is set, and the refrigerant in the second described refrigeration chuck can be silicone oil.
Further, the refrigerant temperature in the second described refrigeration chuck is -10 DEG C~-40 DEG C.
Further, the cannon spray head bottom is provided with the tremie pipe for releasing ice particle.
Further, it is provided with least one on the outside of the roof of the cannon spray head, upper portion side wall and tapered sidewalls
For ice particle being shaken off the vibrator in tremie pipe.
Further, described tremie pipe is connected with described dynamic heat drying device, and be connected
There is valve on pipeline.
Further, described dynamic heat drying device includes outer barrel；Revolution for accommodating simultaneously heated material
Dryer section is divided into outer barrel；For controlling the temperature controlling circulating system of rotary dryer heating-up temperature dry with revolution
Dry device connection.
Further, the outer barrel is a part for closed container, and outer barrel is provided with for connecting vacuum spraying
Freeze the feed pipe of prilling granulator tremie pipe；And for releasing the discharging opening of dried material, discharging opening connection vacuum
Discharging mechanism.
Further, the cannon spray head of the vacuum spraying freezing prilling granulator is outer with dynamic heat drying device
The complete closed container of cylinder connection composition.
Further, the Vacuum discharge mechanism is used to release dried material from vacuum airtight container,
Return to and dispense to rewinding tank under atmospheric pressure or be connected to other material collecting devices, the mechanism is by top discharge valve, slow
Deposit area, multiple pressure pipeline, pump-line and bottom discharge valve group into.
Further, top discharge valve, bottom discharge valve are located at dynamic heat drying device discharging opening lower section,
It is provided with buffer area between top discharge valve, bottom discharge valve, buffer area is by being provided with the pipeline and the dynamic of extraction valve
The outer barrel connection of heat drying apparatus, buffer area is also connected with being provided with the dried and clean aseptic gas access tube of multiple pressure valve
Road；Material collecting device is connected with bottom discharge valve.
Further, the rotary dryer includes the rotating cylinder for accommodating simultaneously heat drying material；For inciting somebody to action
The rotating shaft of rotating cylinder and motor connection；For the motor to rotating shaft powered rotation.
Further, the whole of the rotating cylinder, a part for rotating shaft be in the closed container, the rotating shaft it is another
A part outside closed container with the motor connection.
Further, connected by axle bed between the rotating shaft and outer barrel.
Further, the rotating cylinder outside is provided with least one section hollow jacket, and through-flow body makes barrel in hollow jacket
Heat up or lower the temperature.
Further, the hollow jacket cross sectional shape is rectangle, to surround the rotating cylinder outside shape of a week
Formula is set；Hollow jacket is one or more snippets, arranged in a straight line along its rotation centerline direction；Every section of hollow jacket
Fluid into and out of pipeline is equipped with, internal through-flow body circulation makes barrel heat up or lower the temperature.
Further, the rotating cylinder inwall is provided with least one section of guiding with rotating cylinder rotation centerline at an angle
Groove, when rotating cylinder is rotated forward, material is directed to the direction migration of groove band trend discharging opening；When rotating cylinder is reversely rotated,
Material is brought back.
Further, the temperature controlling circulating system include being sequentially connected one swivel joint of closed-loop path of composition,
Heat exchanger, electric heater and fluid pump, lead to circulation of fluid in closed-loop path.
Further, the swivel joint be side be used for be fixedly connected, side be used for connect revolving body and
Any rotation direction of revolving body continuously or discontinuously trandfer fluid incessantly in rotary motion, conveys electric current incessantly
Device.
Further, path for fluid circulation is provided with inside the rotating shaft, the passage side is described outer
It is connected with one or more snippets hollow jacket on the rotating cylinder in cylinder container；The passage opposite side holds in the outer barrel
Device is outer to be connected with the swivel joint.Swivel joint in any rotation direction of rotating shaft continuously or discontinuously rotary motion,
The fluid in the closed-loop path is set to be conveyed incessantly in the hollow jacket.
Further, the fluid is water or silicone oil.
Further, the detector for detecting material information is provided with the rotating cylinder, described information can be
Temperature；Detector is connected with the swivel joint；The swivel joint in any rotation direction of rotating shaft continuously or discontinuously
Electric current is conveyed in rotary motion incessantly.
Further, the continuous vacuum atomizing freeze drying device also includes for clean water introducing closed container
Inside cleaned, and disinfectant is introduced the washing and sterilizing system sterilized in closed container, the disinfectant
It can be aseptic pure steam.
Further, described continuous vacuum atomizing freeze drying device also includes being used to freeze vacuum spraying
Granulation and dynamic heat drying process carry out the control system of procedure auto-control, and described control system includes can
At least one of programmed logic controller (PLC) and computer (PC).
Present invention also offers a kind of solid pharmaceutical preparation manufacture method, it is characterised in that use above-mentioned solid pharmaceutical preparation
Manufacturing equipment, specific steps include：The solution containing medicine active ingredient, suspension or emulsion are prepared,
Stir or carry out atomizing freeze drying by freeze-drying apparatus of spraying in the state of not stirring, will be through atomizing freeze drying
The particle for obtaining directly is made solid pharmaceutical preparation by solid pharmaceutical preparation shaped device, or, will be through atomizing freeze drying
The particle for obtaining is made solid pharmaceutical preparation after mixing with least one auxiliary material by solid pharmaceutical preparation shaped device.
Preferably, auxiliary material is also contained in described solution, suspension or emulsion.
It is highly preferred that the auxiliary material contained in described solution, suspension or emulsion be adhesive, diluent,
At least one in disintegrant, wetting agent, lubricant and glidant.
Described adhesive be preferably sodium carboxymethylcellulose, dextrin, PVP-K30, PVP K-90,
At least one in Hydroxypropyl methylcellulose and low-substituted hydroxypropyl cellulose, more preferably dextrin, PVP-K30
With at least one in low-substituted hydroxypropyl cellulose.Described diluent is in soluble starch and pregelatinized starch
At least one, more preferably soluble starch.Described disintegrant is sodium carboxymethyl starch and low-substituted hydroxypropyl
At least one in cellulose, more preferably sodium carboxymethyl starch.Described lubricant is preferably magnesium stearate.
Described wetting agent is preferably in Tween-80, Tween-60, Tween-40, Arlacel-80 and Arlacel-60 at least
It is a kind of.Described glidant is preferably talcum powder.
Described medicine active ingredient is the active ingredient of thermal sensitivity or non-heat-sensitive, such as ivy powder, Ah former times
Lip river Wei powder, pancreatin, ROX powder etc..Described is auxiliary with what the particle that atomizing freeze drying is obtained mixed
Expect to be conventional pharmaceutical adjuvants, also can be using the auxiliary material contained in above-mentioned solution, suspension or emulsion.
It is preferably, described that to be made solid pharmaceutical preparation by solid pharmaceutical preparation shaped device be to carry out compressing tablet by tablet press machine
Or capsule is made by capsule filler.
Compared with prior art, the beneficial effects of the invention are as follows：
1) present invention carries out pre-treatment by the way of atomizing freeze drying granulation, ideally combines spraying dry
Dry and two advantages of technology of freeze-drying, had not only avoided influence of the temperature to heat-sensitive substance but also had substantially reduced
The step of pre-treatment (being reduced to 1 step from 4 original steps) and time are (from 15~24h of normal freeze-drying
It is reduced to about 4h), while the stability (RSD ≯ 2.0) between increased the uniformity and batch of mixing, typically
The uniformity of dosage units interval of acceptance of married operation is 85%~115%, RSD ≯ 7.8, and atomizing freeze drying is pelletized
Supplementary material is pelletized under admixture, with more preferable mixed effect, degree of mixing up to 95%~105%,
RSD ≯ 2.0, increase the benefit, reduces cost, can also realize the functions such as closed and on-line cleaning.
2) pretreatment process produced compared to tablet, capsule, is carried out using through atomizing freeze drying particle
Compressing tablet, capsule charge, packaging etc., reduce operational sequence, improve efficiency, reduce cost；
3) compared to conventional pelletization in preparation production, atomizing freeze drying granulation avoids high temperature link,
Heat-sensitive substance is not influenceed, while the control aspect of content uniformity has solely in the material of low content ratio
The advantage for arriving；
| Granulation-drying mode | Conventional temperature (DEG C) |
| Spray-drying process | 80 |
| Conventional ovens are dried | 60 |
| Fluidized bed drying is pelletized | 40~60 |
| Atomizing freeze drying is pelletized | - 40~30 (being adjusted according to actual conditions) |
4) operation such as crushing compared to time-consuming (the about 15~24h) using normal freeze-drying and also needing can just enter
Row compressing tablet, capsule charge etc. operate, atomizing freeze drying have time saving (about 4h), it is laborsaving (save crushing etc.
Operation) clear superiority.
5) being directed to allergenic substance needs the special closed protective effect to reach human body and environment, uses
Atomizing freeze drying particle carries out the operation such as compressing tablet, capsule charge, due to its own distinctive airtight performance, can
To reduce the link of closed-loop operation, security is both improve, cost is reduced again；
6) by atomizing freeze drying granulation material carry out compressing tablet, capsule charge etc. operation, both broken compressing tablet,
The conventional route of the pre-treatment of the research and development such as capsule charge/production, has further expanded atomizing freeze drying granulation
Application category of the technology in production/research fields such as food, medicine, health products, chemical products.
7) present invention it is particularly suitable but be not limited to tool sensitization, content ratio it is low, with bioactivity, heat
Production/the research process of the materials of property such as quick property.The technique has very superior performance, can reduce behaviour
Make operation, improve efficiency, also can well meet the thing with special nature (such as thermal sensitivity, sensitization)
The pretreatment process of material, has expanded the application category of pre-treatment, has a good application prospect.
Brief description of the drawings
Fig. 1 is the batch vacuum spraying freeze drying plant structural representation in embodiment 1.
Fig. 2 is the batch vacuum spraying freeze drying plant structural representation in embodiment 2.
Fig. 3 is the continuous vacuum atomizing freeze drying apparatus structure schematic diagram in embodiment 3；
Fig. 4 is the vacuum spraying freezing prilling granulator structure of the continuous vacuum atomizing freeze drying device in embodiment 3
Schematic diagram；
Fig. 5 is the dynamic heat drying device structural representation of the continuous vacuum atomizing freeze drying device in embodiment 3
Figure.
Fig. 6 is the Vacuum discharge mechanism structure schematic diagram of the continuous vacuum atomizing freeze drying device in embodiment 3.
Fig. 7 is the continuous vacuum atomizing freeze drying apparatus structure schematic diagram in embodiment 4；
Fig. 8 is the vacuum spraying freezing prilling granulator structure of the continuous vacuum atomizing freeze drying device in embodiment 4
Schematic diagram；
Specific embodiment
With reference to specific embodiment, the present invention is expanded on further.It should be understood that these embodiments are merely to illustrate
The present invention rather than limitation the scope of the present invention.In addition, it is to be understood that read instruction of the present invention content it
Afterwards, those skilled in the art can make various changes or modifications to the present invention, and these equivalent form of values equally fall within this
Application appended claims limited range.
Embodiment 1
A kind of solid pharmaceutical preparation manufacturing equipment, by batch vacuum spraying freeze drying plant, mixing arrangement and solid
Preparations shaping device is constituted.Described solid pharmaceutical preparation shaped device is tablet press machine.
As shown in figure 1, described batch vacuum spraying freeze drying plant includes：For cold in vacuum spraying
It is lyophilized it is dry during accommodate the closed container 1 of material；For liquid atomization to be freezed to be separated into drop and spray
Enter the atomizer 2 in described container 1；For being formed in the container 1 in vacuum spraying freezing pelletization stage
Vacuum environment makes the ethanol evaporating heat absorption in described drop and then makes drop cooling freeze to form particle, and dry
The dry stage persistently vacuumizes to maintain the vacuum system of described vacuum environment；And for being freezed in vacuum spraying
Pelletization stage refrigeration is melted and in the particle that drying stage provides described with avoiding the ethanol in described particle
Ethanol distillation heat temperature adjustment chuck 6, and vacuum spraying freeze pelletization stage by vaporization after described in
Drop in ethanol condensation and the particle described in after drying stage is by distillation in ethanol condensation condensation
Device, is provided with described container 1 for rotating to avoid described freezing in vacuum spraying freezing pelletization stage
The particle agglomeration of formation is blocking, and being rotated in drying stage makes described particle roll up and down and described container
The agitating paddle 16 that 1 inwall exchanges heat and makes sublimation gases be escaped from the gap between particle, described agitating paddle
16 bottoms for being located at container 1, described agitating paddle 16 is connected by connecting shaft and motor 7.
Described container 1 is closed container, and top is tubular, and bottom is taper.Described condensing unit is system
Cold chuck 3, described refrigeration chuck 3 is located at the outside on the described top of container 1, the inside of the chuck 3 that freezes
It is connected with refrigerant.Described temperature adjustment chuck 6 is located at the described lower outside of container 1.Described drop is in container 1
Inside not with refrigerant directly contact.
Described refrigeration chuck 3 has refrigerant inlet and refrigerant exit, described refrigerant inlet and refrigerant exit point
Not Lian Jie medium circulation pipeline two ends, described medium circulation pipeline is provided with fluid pump 4 and for refrigerant
The heat exchanger 5 lowered the temperature.The rectangular cross-section of described refrigeration chuck 3, to surround described container 1
The form of the circle of top one set, the refrigerant in described refrigeration chuck is silicone oil.In described temperature adjustment chuck 6
Temperature adjustable fluid is connected with, there is described temperature adjustment chuck 6 temperature adjustable fluid entrance and temperature adjustable fluid to export, described tune
Warm fluid intake and temperature adjustable fluid outlet connect the two ends of temperature adjustable fluid circulation line, described temperature adjustable fluid respectively
Circulation line is provided with fluid pump 4 and heat exchanger 5 and heater 17 for adjusting temperature adjustable fluid temperature.
The rectangular cross-section of described temperature adjustment chuck 6, is set in the form of being enclosed around the bottom one of the container 1；Institute
The temperature adjustable fluid in temperature adjustment chuck 6 stated is silicone oil.The described connection refrigeration system of heat exchanger 5.Described
Refrigeration system is compressor.Interval setting between described refrigeration chuck 3 and temperature adjustment chuck 6.
Described atomizer 2 connects the closed liquid distribution pipe road 8 of liquid to be freezed, described liquid distribution pipe road 8
It is provided with pipeline flow regulating valve 9.Described vacuum system includes vavuum pump 10, and described container 1 is provided with use
In the connector being connected with vavuum pump 10, described vavuum pump 10 connects described container 1 by pipeline 11
Connector, described pipeline 11 is provided with valve 12.The connector of described container 1 is provided with screen pack
13.The bottom of described container 1 is provided with the outlet valve 14 for discharging dry particle.Described outlet valve 14
Can be connected with material collecting device.One is respectively provided with the outside of the roof and upper portion side wall of described container 1 for shaking off
The vibrator 15 of material.Described vibrator 15 is driven by motor and vibrated.The vacuum spraying freeze-drying sets
It is standby also to include introducing clean water being cleaned in described container, and disinfectant is introduced to enter in described container
The washing and sterilizing system of row sterilizing, the disinfectant can be aseptic pure steam.
Described vacuum spraying freezing pelletization stage and drying stage are carried out successively, whole vacuum spraying freeze-drying
Process can be controlled by by the control system being made up of programmable logic controller (PLC) and computer.
Described mixing arrangement and tablet press machine are commercially available prod, the brand of tablet press machine：Tofflon；Model：TSP-58.
Use above-mentioned solid pharmaceutical preparation manufacturing equipment manufacture the method for solid pharmaceutical preparation for：
(1) solution containing medicine active ingredient is prepared：125g ivy powder is dissolved in 2L ethanol,
The ivy ethanol solution that must be clarified is stirred evenly, as liquid to be freezed；
(2) atomizing freeze drying：
Step 1：Pelletization stage is freezed in vacuum spraying, it is -60 DEG C to control the silicone oil temperature in refrigeration chuck 3,
The temperature of silicone oil is -20 DEG C in temperature adjustment chuck 6, is extracted into described closed container 1 first with vacuum system
Certain vacuum, vacuum is 300Pa, and described liquid to be freezed is conveyed into mist by liquid distribution pipe road 8
Change nozzle 2, atomisation pressure is 0.4MPa, and nozzle diameter is 1.0mm, will wait to freeze using atomizer 2
Liquid atomization is separated into drop and sprays into container 1, and the water in drop vaporizes heat absorption in vacuum environment makes drop temperature
Degree declines, and vacuum system is persistently vacuumized, and described refrigeration chuck 3 condenses in container 1 water after vaporization
Vacuum in wall and then the described container 1 of maintenance, drop constant temperature declines up to freezing to form particle, should
Process only needs the several seconds to complete, the particles fall for being formed to the bottom of container 1, and temperature adjustment chuck 6 is to container 1
Bottom refrigeration rotates to keep away to avoid the described ice-out freezed in the particle to be formed, described agitating paddle 16
Freeze the particle agglomeration to be formed into ice cube described in exempting from；
Step 2：In drying stage, spray chilling granulation terminates, and described vacuum system persistently vacuumizes to tie up
The vacuum in container 1 is held, now, vacuum is 100Pa, then described temperature adjustment chuck 6 gradually heats up
The distillation heat of the ice in described particle is provided, heating-up temperature is 35 DEG C, and described agitating paddle 16 persistently turns
It is dynamic cause it is described freeze the particle to be formed and roll up and down sufficiently and uniformly to be exchanged heat with the inwall of container 1, and make liter
Magnificent steam is then condensed from the gap effusion between particle by refrigeration chuck 3, and drying time is 4h, until
Complete dry materials so that the particle to be formed that freezes is completely dried in described container 1.
Step 3：After dry materials, to being passed through dried and clean aseptic gas (such as N in described container 12), make
It is consistent with material collecting device inside and outside differential pressure to realize pressure balance, is then released dried material by outlet valve 14
And dried material is collected by material collecting device.
(3) solid pharmaceutical preparation shaping：Using mixing arrangement by gained dried material 108g and 45g microcrystalline celluloses
(MCC), 40g sodium carboxymethyl starches (CMS-Na), 15g superfine silica gel powders, the mixing of 2g magnesium stearates, adopt
Compressing tablet is carried out with tablet press machine, smooth appearance, complete, the uniform tablet of weight is obtained.
Embodiment 2
A kind of solid pharmaceutical preparation manufacturing equipment, by batch vacuum spraying freeze drying plant and solid pharmaceutical preparation shaping dress
Put composition.Described solid pharmaceutical preparation shaped device be capsule filler (Capsule filler brand：Fu Chang；Model： 120C)。
As shown in Fig. 2 described batch vacuum spraying freeze drying plant includes：For cold in vacuum spraying
It is lyophilized it is dry during accommodate the closed container 1 of material；For liquid atomization to be freezed to be separated into drop and spray
Enter the atomizer 2 in described container 1；For being formed in the container 1 in vacuum spraying freezing pelletization stage
Vacuum environment makes the water vapor heat absorption in described drop and then makes drop cooling freeze to form particle, and in drying
Stage persistently vacuumizes to maintain the vacuum system of described vacuum environment；And for being made in vacuum spraying freezing
The grain stage freezes to avoid water thawing and the water in the particle that drying stage provides described in described particle
Distillation heat temperature adjustment chuck 6, and vacuum spraying freeze pelletization stage by vaporization after described in drop
Water vapour condensation and the particle described in after drying stage is by distillation in water vapour condensation condensing unit,
It is provided with described container 1 for rotating to avoid described freezing to be formed in vacuum spraying freezing pelletization stage
Particle agglomeration it is blocking, and being rotated in drying stage makes described particle roll up and down and described container 1
The agitating paddle 16 that inwall exchanges heat and makes sublimation gases be escaped from the gap between particle, described agitating paddle 16
In the bottom of container 1, described agitating paddle 16 is connected by connecting shaft and motor 7.
Described container 1 is closed container, and top is tubular, and bottom is taper.Described condensing unit is to set
Condenser 30 that is outer in described container 1 and being connected with described container 1, described condenser 30 is by pipe
Road 11 connects the connector of described container 1, and described vavuum pump 10 connects condenser by another pipeline
30, the pipeline 11 between described condenser 30 and the connector of described container 1 is provided with valve 12,
The chuck that freezes is not provided with the outside of the top of container 1.Described temperature adjustment chuck 6 is outside the described bottom of container 1
Side.Described drop in the container 1 not with refrigerant directly contact.Temperature adjustment stream is connected with described temperature adjustment chuck 6
There is body, described temperature adjustment chuck 6 temperature adjustable fluid entrance and temperature adjustable fluid to export, described temperature adjustable fluid entrance
The two ends for connecting temperature adjustable fluid circulation line respectively are exported with temperature adjustable fluid, on described temperature adjustable fluid circulation line
It is provided with fluid pump 4 and heat exchanger 5 and heater 17 for adjusting temperature adjustable fluid temperature.Described temperature adjustment
The rectangular cross-section of chuck 6, is set in the form of being enclosed around the bottom one of the container 1；Described temperature adjustment folder
Temperature adjustable fluid in set 6 is silicone oil.The described connection refrigeration system of heat exchanger 5.Described refrigeration system is
Compressor.
Described atomizer 2 connects the closed liquid distribution pipe road 8 of liquid to be freezed, described liquid distribution pipe road 8
It is provided with pipeline flow regulating valve 9.Described vacuum system includes vavuum pump 10, and described container 1 is provided with use
In the connector being connected with vavuum pump 10, described vavuum pump 10 connects described container 1 by pipeline 11
Connector, described pipeline 11 is provided with valve 12.The connector of described container 1 is provided with screen pack
13.The bottom of described container 1 is provided with the outlet valve 14 for discharging dry particle.Described outlet valve 14
Can be connected with material collecting device.One is respectively provided with the outside of the roof and upper portion side wall of described container 1 for shaking off
The vibrator 15 of material.Described vibrator 15 is driven by motor and vibrated.The vacuum spraying freeze-drying sets
It is standby also to include introducing clean water being cleaned in described container, and disinfectant is introduced to enter in described container
The washing and sterilizing system of row sterilizing, the disinfectant can be aseptic pure steam.
Described vacuum spraying freezing pelletization stage and drying stage are carried out successively, whole vacuum spraying freeze-drying
Process can be controlled by by the control system being made up of programmable logic controller (PLC) and computer.
Use above-mentioned solid pharmaceutical preparation manufacturing equipment manufacture the method for solid pharmaceutical preparation for：
(1) suspension containing medicine active ingredient and auxiliary material is prepared：By pancreatin 200g, isopropanol 40ml,
60g 30 POVIDONE K 30 BP/USPs -60 (PVP-K30) are scattered in 2L water, obtain liquid to be freezed；
(2) atomizing freeze drying：
Step 1：Pelletization stage is freezed in vacuum spraying, the temperature of silicone oil in temperature adjustment chuck 6 is controlled for -20 DEG C,
Described closed container 1 is extracted into certain vacuum first with vacuum system, vacuum is 300Pa, led to
Cross liquid distribution pipe road 8 and described liquid to be freezed is conveyed to atomizer 2, atomisation pressure is 0.5MPa, spray
The a diameter of 1.5mm of mouth, liquid atomization to be freezed using atomizer 2 be separated into drop and spray into container 1,
Water in drop vaporizes heat absorption in vacuum environment makes drop temperature drop, and vacuum system is persistently vacuumized, described
Condenser 30 water after vaporization is condensed in into the inwall of container 1 and then the vacuum in described container 1 is maintained,
Drop constant temperature declines until freezing to form particle, the process only needs the several seconds to complete, the particles fall for being formed
To the bottom of container 1, temperature adjustment chuck 6 is to the bottom refrigeration of container 1 avoiding described freezing the particle to be formed
In ice-out, described agitating paddle 16 rotates to avoid described freezing the particle agglomeration to be formed into ice cube；
Step 2：In drying stage, spray chilling granulation terminates, and described vacuum system persistently vacuumizes to tie up
The vacuum in container 1 is held, now, vacuum is 100Pa, then described temperature adjustment chuck 6 gradually heats up
The distillation heat of the ice in described particle is provided, heating-up temperature is 30 DEG C, and described agitating paddle 16 persistently turns
It is dynamic cause it is described freeze the particle to be formed and roll up and down sufficiently and uniformly to be exchanged heat with the inwall of container 1, and make liter
Magnificent steam is then condensed from the gap effusion between particle by condenser 30, and drying time is 4h, until complete
Into dry materials so that the particle to be formed that freezes is completely dried in described container 1.
Step 3：After dry materials, to being passed through dried and clean aseptic gas (N in described container 12), make it
It is consistent with material collecting device inside and outside differential pressure to realize pressure balance, dried material is released simultaneously by outlet valve 14 then
Dried material is collected by material collecting device.
(3) solid pharmaceutical preparation shaping：The particle 237g of gained is directly carried out into capsule charge using capsule filler,
Obtain weight uniform, smooth appearance, complete pancreatin capsules.
Embodiment 3
A kind of solid pharmaceutical preparation manufacturing equipment, by continuous vacuum atomizing freeze drying device, mixing arrangement and solid
Preparations shaping device is constituted.Described solid pharmaceutical preparation shaped device be capsule filler (Capsule filler brand： Fu Chang；Model：120C)。
As shown in figure 3, described continuous vacuum atomizing freeze drying device, including be in turn connected to form closed
The vacuum spraying of container freezes prilling granulator 100, dynamic heat drying device 200 and Vacuum discharge mechanism 300.
With reference to Fig. 4, vacuum spraying freezing prilling granulator 100 is included for accommodating product during mist projection granulating
Cannon spray head 1-1；Multiple is used to that liquid to be freezed atomization to be separated into drop and the mist in cannon spray head 1-1 is sprayed into
Change nozzle 1-2；It is true at this for forming the constituent part during vacuum environment makes described drop in closed container
Heat absorption is vaporized in Altitude and then drop is lowered the temperature and freeze to form the vacuum system of ice particle；And for that will vaporize
The condensing unit of the constituent part condensation in described drop afterwards.Described atomizer 1-2 is located at cannon spray head
In 1-1.Described vacuum system is connected with cannon spray head 1-1.
Described cannon spray head 1-1 tops are tubular, and bottom is taper.Described condensing unit is located at cannon spray head
The first refrigeration chuck 1-3 of refrigerant is passed through on the outside of 1-1 tops, refrigerant is silicone oil.Silicone oil is by pipeline
Fluid pump 1-4 is formed and is circulated and lowered the temperature by heat exchanger 1-5.The rectangular cross-section of the first refrigeration chuck 1-3,
Set in the form of being enclosed around the top one of cannon spray head 1-1.Cannon spray head 1-1 lower taper outside be provided with for
The second refrigeration chuck 1-6 that ice particle melts is avoided, refrigerant is passed through in it for silicone oil.Silicone oil is by another group of pipe
Fluid pump 1-4 on road is formed and is circulated and lowered the temperature by heat exchanger 1-5.The section of the second refrigeration chuck 1-6
It is rectangle, is set with the form of the circle of cannon spray head 1-1 lower tapers outside one.Two described heat exchangers
1-5 connects refrigeration system 1-7.Described refrigeration system 1-7 is compressor.
Described atomizer 1-2 connects closed liquid distribution pipe road 1-8, and liquid to be freezed is passed through in pipeline, matches somebody with somebody
Liquid pipe road 1-8 is provided with flow control valve 1-9.Described vacuum system includes vavuum pump 1-10, with cannon spray head
1-1 is connected by pipeline 1-11, and described pipeline 1-11 is provided with valve 1-12.The connector of cannon spray head 1-1
It is provided with screen pack 1-13.
The bottom of described cannon spray head 1-1 is provided with the outlet valve 1-14 for releasing ice particle, cannon spray head 1-1's
A vibrator 1-15 for ice particle to be shaken off is respectively provided with the outside of roof, upper portion side wall and lower sides.
Described vibrator 1-15 is driven by motor and vibrated.Described outlet valve 1-14 is done by pipeline with dynamic heat
Dry device connection.
As shown in figure 5, described dynamic heat drying device 200 includes：Outer barrel 2-1, feed pipe 2-2,
Discharging opening 2-4, discharging opening has valve；The cannon spray head 1-1 is connected by outlet valve 1-14 with feed pipe 2-2,
Material is not by environmental pollution or pollution ring in cannon spray head 1-1 and outer barrel 2-1 composition closed containers and protective container
Border；By rotating cylinder 2-11, rotating shaft 2-12, motor 2-13, and the rotary dryer that at least one axle bed is constituted,
Rotating cylinder 2-11 is used to accommodate and heat drying material, and rotating shaft 2-12 is used to pass to motor 2-13 rotary powers
Rotating cylinder 2-11；It is made up of swivel joint 2-21, heat exchanger 2-22, electric heater 2-23, fluid pump 2-24
Temperature controlling circulating system.
Rotating cylinder 2-11 outsides are provided with least one section hollow jacket 2-15, every section of hollow jacket 2-15 and pass through pipeline
It is connected with the passage inside rotating shaft 2-12, and the whole of rotating cylinder 2-11, a part of rotating shaft 2-12 are arranged on
In closed container；Another part of rotating shaft 2-12 is connected outside closed container with motor 2-13, and the part
Inner passage be connected with swivel joint 2-21；Described swivel joint 2-21 is that side is used to be fixedly connected,
Opposite side is used for connection rotating shaft 2-12 and defeated incessantly in its any rotation direction continuously or discontinuously rotary motion
Fluid is sent, the device of electric current is conveyed incessantly.Fluid is passed through in described temperature controlling circulating system for silicone oil, silicon
Oil is heated by electric heater 2-23 and adjusts temperature by heat exchanger 2-22 and carried out by fluid pump 2-24
Circulating makes hollow jacket 2-15 barrels heat up or lower the temperature.
As shown in fig. 6, described Vacuum discharge mechanism 300 includes the top discharge valve below discharging opening 2-4
3-1, bottom discharge valve 3-2, and the buffer area 3-3 between two outlet valves, buffer area 3-3 is by with extraction valve
The pipeline of 3-5 is connected with closed container, and buffer area 3-3 is also connected with being passed through dried and clean with multiple pressure valve 3-6
The pipeline of aseptic gas；Rewinding tank 3-4 is connected with bottom discharge valve 3-2.
Clean water can be also passed through in the closed container of described equipment for cleaning container, can be passed through disinfectant is used for
Sterilizing containers, the preferred sterile steam of disinfectant.
Described solid pharmaceutical preparation manufacturing equipment is in freeze-drying process by by programmable logic controller (PLC) and computer
The control system of composition carries out Automated condtrol.
Use above-mentioned solid pharmaceutical preparation manufacturing equipment manufacture the method for solid pharmaceutical preparation for：
(1) emulsion containing medicine active ingredient and auxiliary material is prepared：By 100g ROXs powder, 10g
Sodium carboxymethyl starch (CMS-Na), 20g Tween-80s are scattered in 2L water, obtain liquid to be freezed.
(2) atomizing freeze drying：
Step 1：The closed container that described cannon spray head 1-1 and outer barrel 2-1 is constituted is taken out first with vacuum system
To negative pressure, vacuum is 300Pa.
Step 2：The first described refrigeration chuck 1-3 temperature controls are -60 DEG C, the second refrigeration chuck 1-6 temperature
It is controlled to -20 DEG C；Described liquid to be freezed is conveyed to by atomizer 1-2 by liquid distribution pipe road 1-8, is sprayed
Pressure is 0.35MPa, and nozzle diameter is 1.2mm, is atomized the liquid into using atomizer 1-2 and is separated into drop
And cannon spray head 1-1 is sprayed into, heat absorption makes drop temperature drop, vacuum after the water in drop is vaporized in vacuum environment
Systems stay is vacuumized, and the water after vaporization is condensed in cannon spray head 1-1 inwalls by the first described refrigeration chuck 1-3
And then vacuum is maintained, drop constant temperature declines up to freezing to form ice particle, and the process only needs the several seconds to complete,
Ice particle is shaken off into cannon spray head 1-1 bottoms by the effect of vibration of vibrator 1-15 to release.Described drop
It is not frozen with refrigerant directly contact in cannon spray head 1-1.
Step 3：The ice particle of material is added in rotating cylinder 2-11 by feed pipe 2-2.Described rotating cylinder 2-11
It is 40 DEG C that a certain section of hollow jacket 2-15 controls heating-up temperature by temperature controlling circulating system；Rotating cylinder 2-11 is in drying
During persistently rotate, material cylinder bottom roll, sufficiently uniformly contacted with barrel and be heated；Gathering sill
2-14 with rotating cylinder rotation material is taken up from cylinder bottom, material from Action of Gravity Field on gathering sill to discharging opening
2-4 directions are slided, and gathering sill continues to rotate with rotating cylinder, and material falls revolving drum bottom, passes through by Action of Gravity Field
The Liquid addition of control flow control valve 1-9 makes material be migrated to discharging opening with appropriate speed with rotating cylinder rotating speed
And uniformly dispersing does not form accumulation in cylinder bottom；Sublimation gases are quick to be arranged from surface of material and particulate interspaces
To go out taken away by vacuum system and condense in cannon spray head 1-1 upper inside walls；Material is rolled by rotating cylinder rotation lasts
The compound motion for progressively being migrated to discharging opening, gradually dries, in rotating cylinder until being completely dried, drying time
It is 4h.
Step 4：Dried material is dropped in discharging opening 2-4 from rotating cylinder 2-11；When needing discharging, in opening
Outlet valve 3-1, material is fallen into buffer area 3-3, closes top discharge valve 3-1, extraction valve 3-5；Open multiple pressure
Valve 3-6, dried and clean aseptic gas are passed through to buffer area, make external pressure in buffer area 3-3 and material collecting device 3-4
Difference is consistent；Bottom discharge valve 3-2 is opened, dried material, thing in buffer area 3-3 are collected by material collecting device 3-4
Bottom discharge valve, multiple pressure valve are closed after material emptying, extraction valve is opened, and change material collecting device；Need to go out again
During material, the step is repeated.
(3) solid pharmaceutical preparation shaping：Particle 182g and 100g low-substituted hydroxypropyls as mixing arrangement by obtained by
After cellulose mixing, capsule charge is carried out by capsule filler, it is uniform to obtain weight, it is smooth appearance, complete
Roxithromycin capsules.
Embodiment 4
A kind of solid pharmaceutical preparation manufacturing equipment, by continuous vacuum atomizing freeze drying device and solid pharmaceutical preparation shaping dress
Put composition.Described solid pharmaceutical preparation shaped device is tablet press machine (tablet press machine brand：Tofflon；Model：TSP-58).
As shown in fig. 7, the difference of described continuous vacuum atomizing freeze drying device Yu embodiment 3 is true
Empty spray chilling prilling granulator part.
As shown in figure 8, described vacuum spraying freezes prilling granulator similar to embodiment 1, difference is：Institute
The condensing unit stated is outside cannon spray head 1-1 and connected condenser 1-30, described condenser 1-30
The connector of cannon spray head 1-1 is connected by pipeline 1-11, described vavuum pump 1-10 is connected by another pipeline
The connecting pipe 1-11 of condenser 1-30, condenser 1-30 and cannon spray head 1-1 is provided with valve 1-12, spraying
Cylinder 1-1 is not provided with the first refrigeration chuck 1-3 on the outside of top.
Use above-mentioned solid pharmaceutical preparation manufacturing equipment manufacture the method for solid pharmaceutical preparation for：
(1) suspension containing medicine active ingredient and auxiliary material is prepared：By 10g ACVs powder and 290g
Dextrin is scattered in 2L water, obtains liquid to be freezed；
(2) atomizing freeze drying：
Step 1：The closed container that described cannon spray head 1-1 and outer barrel 2-1 is constituted is taken out first with vacuum system
To negative pressure, vacuum is 300Pa.
Step 2：The second described refrigeration chuck 1-6 temperature controls are -20 DEG C；By liquid distribution pipe road 1-8 by institute
The liquid to be freezed stated is conveyed to atomizer 1-2, and atomisation pressure is 0.6MPa, and nozzle diameter is 2.0mm,
Atomized the liquid into using atomizer 1-2 and be separated into drop and spray into cannon spray head 1-1, the water in drop is in vacuum
Heat absorption makes drop temperature drop after being vaporized in environment, and vacuum system is persistently vacuumized, described condenser 1-30
Water after vaporization is condensed in into cannon spray head 1-1 inwalls and then vacuum is maintained, drop constant temperature declines until freezing
Knot forms ice particle, and the process only needs the several seconds to complete, and is shaken ice particle by the effect of vibration of vibrator 1-15
Fall the releasing of cannon spray head 1-1 bottoms.Described drop is not frozen in cannon spray head 1-1 with refrigerant directly contact
Knot.
Step 3：The ice particle of material is added in rotating cylinder 2-11 by feed pipe 2-2.Described rotating cylinder 2-11
It is 40 DEG C that a certain section of hollow jacket 2-15 controls heating-up temperature by temperature controlling circulating system；Rotating cylinder 2-11 is in drying
During persistently rotate, material cylinder bottom roll, sufficiently uniformly contacted with barrel and be heated；Gathering sill
2-14 with rotating cylinder rotation material is taken up from cylinder bottom, material from Action of Gravity Field on gathering sill to discharging opening
2-4 directions are slided, and gathering sill continues to rotate with rotating cylinder, and material falls revolving drum bottom, passes through by Action of Gravity Field
The Liquid addition of control flow control valve 1-9 makes material be migrated to discharging opening with appropriate speed with rotating cylinder rotating speed
And uniformly dispersing does not form accumulation in cylinder bottom；Sublimation gases are quick to be arranged from surface of material and particulate interspaces
To go out taken away by vacuum system and condense in cannon spray head 1-1 upper inside walls；Material is rolled by rotating cylinder rotation lasts
The compound motion for progressively being migrated to discharging opening, gradually dries, in rotating cylinder until being completely dried, drying time
It is 3.5h.
Step 4：Dried material is dropped in discharging opening 2-4 from rotating cylinder 2-11；When needing discharging, in opening
Outlet valve 3-1, material is fallen into buffer area 3-3, closes top discharge valve 3-1, extraction valve 3-5；Open multiple pressure
Valve 3-6, dried and clean aseptic gas are passed through to buffer area, make external pressure in buffer area 3-3 and material collecting device 3-4
Difference is consistent；Bottom discharge valve 3-2 is opened, dried material, thing in buffer area 3-3 are collected by material collecting device 3-4
Bottom discharge valve, multiple pressure valve are closed after material emptying, extraction valve is opened, and change material collecting device；Need to go out again
During material, the step is repeated.
(3) solid pharmaceutical preparation shaping：The particle 278g of gained is directly carried out into compressing tablet using tablet press machine, obtains outer
The sightseeing uniform tablet of clean, complete, weight.
Comparative example 1
10g ACVs powder is first mixed with 140g dextrin using conventional wet lay granulation, pelletized, done
Compressing tablet is carried out after dry, whole grain, then after mixing with remaining 150g dextrin.
Particle before the compressing tablet obtained to embodiment 4 and comparative example 1 carries out degree of mixing measure, determines three times,
Comparing result see the table below.
Result shows, although relatively, but the RSD values of embodiment 4 are obviously reduced degree of mixing average, have
More preferable accuracy and accuracy, therefore with more preferable uniformity of dosage units.
Claims (10)
1. a kind of solid pharmaceutical preparation manufacturing equipment, it is characterised in that including spraying freeze-drying apparatus and solid pharmaceutical preparation into
Type device.
2. solid pharmaceutical preparation manufacturing equipment as claimed in claim 1, it is characterised in that also including mixing arrangement.
3. solid pharmaceutical preparation manufacturing equipment as claimed in claim 1, it is characterised in that not including mixing arrangement.
4. solid pharmaceutical preparation manufacturing equipment as claimed in claim 1, it is characterised in that described solid pharmaceutical preparation
Shaped device is tablet press machine or capsule filler.
5. solid pharmaceutical preparation manufacturing equipment as claimed in claim 1, it is characterised in that described spraying is freezed
Device is batch vacuum spraying freeze drying plant or continuous vacuum atomizing freeze drying device；Described criticizes
Secondary formula vacuum spraying freeze drying plant includes：For accommodating the close of material in vacuum spraying freezing dry process
The container for closing；For liquid to be freezed atomization to be separated into drop and the atomizer in described container is sprayed into；
For forming the part group during vacuum environment makes described drop in a reservoir in vacuum spraying freezing pelletization stage
Divide vaporization heat absorption and then drop is lowered the temperature and freeze to form particle, and in the vacuum environment described in drying stage maintenance
Vacuum system；And for freezing to avoid the part group in described particle in vacuum spraying freezing pelletization stage
Divide the temperature adjustment chuck of the distillation heat of the constituent part melted and in the particle that drying stage provides described；It is described
Continuous vacuum atomizing freeze drying device include interconnect composition closed container vacuum spraying freezing make
Grain device and dynamic heat drying device；Described vacuum spraying freezing prilling granulator includes cannon spray head, the spray
The atomizer for liquid to be freezed atomization to be separated into drop is provided with mist cylinder, the cannon spray head is connected to
The constituent part formed in closed container during vacuum environment makes described drop vaporizes suction in the vacuum environment
Heat so make drop lower the temperature freeze to form the vacuum system of ice particle.
6. a kind of solid pharmaceutical preparation manufacture method, it is characterised in that using any one of claim 1-5
Solid pharmaceutical preparation manufacturing equipment, specific steps include：Prepare the solution containing medicine active ingredient, suspension or
Emulsion, atomizing freeze drying is carried out in the state of not stirring in stirring or by freeze-drying apparatus of spraying, will be through spray
The particle that mist freeze-drying is obtained directly is made solid pharmaceutical preparation by solid pharmaceutical preparation shaped device, or, will be through spray
The particle that mist freeze-drying is obtained is made solid after mixing with least one auxiliary material by solid pharmaceutical preparation shaped device
Preparation.
7. solid pharmaceutical preparation manufacture method as claimed in claim 6, it is characterised in that described solution, mixed
Also contain auxiliary material in suspension or emulsion.
8. solid pharmaceutical preparation manufacture method as claimed in claim 7, it is characterised in that described solution, mixed
The auxiliary material contained in suspension or emulsion be adhesive, diluent, disintegrant, lubricant and glidant in extremely
Few one kind.
9. solid pharmaceutical preparation manufacture method as claimed in claim 8, it is characterised in that described adhesive is
Sodium carboxymethylcellulose, dextrin, PVP-K30, PVP K-90, Hydroxypropyl methylcellulose and low substitution hydroxyl
At least one in third cellulose；Described diluent is at least in soluble starch and pregelatinized starch
Kind；Described disintegrant is at least one in sodium carboxymethyl starch and low-substituted hydroxypropyl cellulose；Described profit
Lubrication prescription is magnesium stearate；Described wetting agent is Tween-80, Tween-60, Tween-40, Arlacel-80 and sapn
At least one in -60；Described glidant is talcum powder.
10. solid pharmaceutical preparation manufacture method as claimed in claim 6, it is characterised in that described by solid
It is by tablet press machine to carry out compressing tablet or be made capsule by capsule filler that preparations shaping device is made solid pharmaceutical preparation.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510790262.7A CN106705574A (en) | 2015-11-17 | 2015-11-17 | Solid preparation fabrication equipment and method |
| PCT/CN2015/098805 WO2017084160A1 (en) | 2015-11-17 | 2015-12-24 | Solid formulation preparation apparatus and method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510790262.7A CN106705574A (en) | 2015-11-17 | 2015-11-17 | Solid preparation fabrication equipment and method |
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| CN106705574A true CN106705574A (en) | 2017-05-24 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN201510790262.7A Pending CN106705574A (en) | 2015-11-17 | 2015-11-17 | Solid preparation fabrication equipment and method |
Country Status (2)
| Country | Link |
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| CN (1) | CN106705574A (en) |
| WO (1) | WO2017084160A1 (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110123634A (en) * | 2018-02-09 | 2019-08-16 | 株式会社理光 | The manufacturing method of particle, the manufacturing device and particle of particle |
| CN111714375A (en) * | 2020-07-02 | 2020-09-29 | 于娟 | Azithromycin dispersible tablet preparation system |
| CN113729010A (en) * | 2021-09-17 | 2021-12-03 | 重庆文理学院 | Production equipment and method of freeze-dried biological pesticide effervescent granules |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108571874A (en) * | 2018-07-05 | 2018-09-25 | 福建泰达高新材料有限公司 | A kind of HIGH-PURITY SILICON production drying unit |
| CN108946175B (en) * | 2018-07-26 | 2023-08-25 | 常州朗脉洁净技术有限公司 | Continuous discharging system for material dust of vacuum belt dryer |
| CN114191541A (en) * | 2020-09-02 | 2022-03-18 | 齐鲁制药有限公司 | Preparation of Somalutide particles by spray freeze-drying method |
| CN114522617A (en) * | 2022-01-07 | 2022-05-24 | 上海康识食品科技有限公司 | Flavor particle and granulation method thereof |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1899400A (en) * | 2006-07-14 | 2007-01-24 | 天津市轩宏医药技术有限公司 | Medicinal preparation containing ginseng and aconite root in raw material and its preparing method and quality control method |
| CN101680714A (en) * | 2007-06-14 | 2010-03-24 | 株式会社爱发科 | Vacuum freeze-drying apparatus and method of vacuum freeze drying |
| CN101713607A (en) * | 2009-12-16 | 2010-05-26 | 中国林业科学研究院林产化学工业研究所 | Method for producing powder through decompression, atomization, freezing and drying and device |
| CN103069240A (en) * | 2010-08-04 | 2013-04-24 | Ima生命北美股份有限公司 | Bulk freeze drying using spray freezing and stirred drying |
| CN103917841A (en) * | 2011-10-05 | 2014-07-09 | 赛诺菲巴斯德有限公司 | Process line for the production of freeze-dried particles |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2471035A (en) * | 1943-10-02 | 1949-05-24 | Frank E Hurd | Apparatus for the desiccation of organic substances |
| US3396475A (en) * | 1966-01-10 | 1968-08-13 | Scheibel Edward George | Freeze drying system |
| US5230162A (en) * | 1992-06-26 | 1993-07-27 | Oyler Jr James R | Systems and methods for the deliquification of liquid-containing substances by flash sublimation |
| NL1022668C2 (en) * | 2003-02-13 | 2004-08-16 | Hosokawa Micron B V | Stirred freeze drying. |
-
2015
- 2015-11-17 CN CN201510790262.7A patent/CN106705574A/en active Pending
- 2015-12-24 WO PCT/CN2015/098805 patent/WO2017084160A1/en active Application Filing
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1899400A (en) * | 2006-07-14 | 2007-01-24 | 天津市轩宏医药技术有限公司 | Medicinal preparation containing ginseng and aconite root in raw material and its preparing method and quality control method |
| CN101680714A (en) * | 2007-06-14 | 2010-03-24 | 株式会社爱发科 | Vacuum freeze-drying apparatus and method of vacuum freeze drying |
| CN101713607A (en) * | 2009-12-16 | 2010-05-26 | 中国林业科学研究院林产化学工业研究所 | Method for producing powder through decompression, atomization, freezing and drying and device |
| CN103069240A (en) * | 2010-08-04 | 2013-04-24 | Ima生命北美股份有限公司 | Bulk freeze drying using spray freezing and stirred drying |
| CN103917841A (en) * | 2011-10-05 | 2014-07-09 | 赛诺菲巴斯德有限公司 | Process line for the production of freeze-dried particles |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110123634A (en) * | 2018-02-09 | 2019-08-16 | 株式会社理光 | The manufacturing method of particle, the manufacturing device and particle of particle |
| US11285111B2 (en) | 2018-02-09 | 2022-03-29 | Ricoh Company, Ltd. | Particle-producing method and particle-producing apparatus |
| CN111714375A (en) * | 2020-07-02 | 2020-09-29 | 于娟 | Azithromycin dispersible tablet preparation system |
| CN113729010A (en) * | 2021-09-17 | 2021-12-03 | 重庆文理学院 | Production equipment and method of freeze-dried biological pesticide effervescent granules |
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| Publication number | Publication date |
|---|---|
| WO2017084160A1 (en) | 2017-05-26 |
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Application publication date: 20170524 |