CN113636519B - Sterile production method of aerosol - Google Patents
Sterile production method of aerosol Download PDFInfo
- Publication number
- CN113636519B CN113636519B CN202010345050.9A CN202010345050A CN113636519B CN 113636519 B CN113636519 B CN 113636519B CN 202010345050 A CN202010345050 A CN 202010345050A CN 113636519 B CN113636519 B CN 113636519B
- Authority
- CN
- China
- Prior art keywords
- aerosol
- liquid
- pentafluoropropane
- temperature
- propellant
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Images
Classifications
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B67—OPENING, CLOSING OR CLEANING BOTTLES, JARS OR SIMILAR CONTAINERS; LIQUID HANDLING
- B67C—CLEANING, FILLING WITH LIQUIDS OR SEMILIQUIDS, OR EMPTYING, OF BOTTLES, JARS, CANS, CASKS, BARRELS, OR SIMILAR CONTAINERS, NOT OTHERWISE PROVIDED FOR; FUNNELS
- B67C7/00—Concurrent cleaning, filling, and closing of bottles; Processes or devices for at least two of these operations
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B67—OPENING, CLOSING OR CLEANING BOTTLES, JARS OR SIMILAR CONTAINERS; LIQUID HANDLING
- B67C—CLEANING, FILLING WITH LIQUIDS OR SEMILIQUIDS, OR EMPTYING, OF BOTTLES, JARS, CANS, CASKS, BARRELS, OR SIMILAR CONTAINERS, NOT OTHERWISE PROVIDED FOR; FUNNELS
- B67C7/00—Concurrent cleaning, filling, and closing of bottles; Processes or devices for at least two of these operations
- B67C7/0073—Sterilising, aseptic filling and closing
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Vacuum Packaging (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention discloses a sterile production method of aerosol, which comprises the steps of freezing a propellant into liquid and then filling the liquid into a sterile tank. The propellant is frozen into liquid for sterilization and filtration, so that the sterility of liquid medicine and the sterility of production equipment are realized; the lengthened and widened tunnel oven is adopted, so that the aerosol can meets the requirement of dry heat sterilization at 170-180 ℃ for 1 hour, and the online sterilization production of the aerosol can is realized.
Description
Technical Field
The invention relates to the technical field of aerosol production, in particular to an aseptic production method of an aerosol.
Background
In the aseptic production process of the specific aerosol, the propellant in the aerosol is compressed and then filled, but raw materials and production equipment of the compressed propellant cannot be effectively sterilized and cleaned, so that the production of the aseptic aerosol is not facilitated. In addition, the temperature and time of the conventional aerosol washing and drying tank can not reach the level of 170-180 ℃ for 1 hour of dry heat sterilization, and other sterilization modes are not favorable for the aseptic guarantee of online production, so that the aseptic production of the aerosol is difficult to realize. The sterilization method adopted at present avoids the problem that the equipment cannot be produced and filled aseptically in the new inspection center of southwest information center of 7-month-science and technology in 2019, and the new inspection shows that the related literature research report in China is not seen.
Disclosure of Invention
The invention aims to provide an aseptic production method of aerosol, which solves the problem that equipment for compressing a propellant cannot be effectively sterilized in the prior art, so that the aseptic aerosol production is not facilitated.
In order to solve the technical problems, the invention adopts the following technical scheme:
a sterile production method of aerosol includes freezing propellant into liquid, filtering, sterilizing, and aseptic canning.
Preferably, the propellant comprises at least one of ethane, propane and hydrofluorocarbons having a carbon chain length greater than 4.
Preferably, the propellant is at least one of tetrafluoroethane, propane, n-butane, isobutane, chloroethane and pentafluoropropane.
Preferably, the tetrafluoroethane, propane, n-butane, isobutane and chloroethane are stored for more than 4 hours at the temperature of-5 to 5 ℃ before being filled, and the pentafluoropropane is stored for more than 8 hours at the temperature of 18 to 28 ℃ before being filled.
Preferably, the liquid preparation is carried out before filling, wherein the liquid preparation is carried out by cooling pentafluoropropane to below 18 ℃, and then uniformly mixing the cooled pentafluoropropane with quantitative tetrafluoroethane, propane, n-butane, chloroethane or isobutane to obtain a mixed liquid, and the temperature of the mixed liquid is-10 ℃.
Preferably, the liquid preparation is carried out in a liquid preparation room, wherein the temperature of the liquid preparation room is 10-28 ℃, the relative humidity is 35-75%, and the relative negative pressure is more than or equal to 5Pa.
Preferably, the mixture is filtered through one or more stages of 0.22 μm filter cartridges and filled into aerosol cans.
Preferably, the injection water injection preparation method further comprises the steps of adding raw and auxiliary materials into the injection water preparation liquid, and then performing sterilization filtration and filling.
Preferably, before filling, the aerosol can is cleaned and dried, and then a tunnel oven with the length of 3.8-5.2 meters and the width of 0.8-1.2 meters is adopted to carry out dry heat sterilization for 1h under the protection of a class-A or class-A laminar flow at 170-180 ℃. The aerosol can, the filling liquid medicine, the propellant, the installation of the aerosol valve, the valve actuator and the like can be subjected to dry heat sterilization for 1h under the protection of 100-level or A-level laminar flow, thereby ensuring that the product achieves the aim of sterility
Preferably, the aerosol valve, valve actuator, cap associated with the aerosol canister is sterilized by cobalt 60 irradiation prior to assembly.
Compared with the prior art, the invention has the beneficial effects that at least one of the following is adopted:
the propellant is frozen into liquid for sterilization and filtration, so that the sterility of liquid medicine and the sterility of production equipment are realized.
The method adopts the lengthened and widened tunnel oven with the length of 3.8-5.2 meters and the width of 0.8-1.2 meters, so that the aerosol can meets the requirement of dry heat sterilization at 170-180 ℃ for 1 hour, and the online sterilization production of the aerosol can is realized.
The conventional aerosol filling propellant filling equipment is omitted, and the problem that the equipment cannot realize sterile filling is avoided.
The air-drying aerosol can, the filling liquid medicine, the propellant, the installation of the aerosol valve, the valve actuator and the like are produced under the protection of the class 100 or class A laminar flow, so that the aim of sterility of the product is ensured.
The propellant is only used for producing the sterile aerosol without adding raw materials and auxiliary materials.
Drawings
FIG. 1 is a process flow diagram of the present invention.
Detailed Description
The present invention will be described in further detail with reference to the drawings and examples, in order to make the objects, technical solutions and advantages of the present invention more apparent. It should be understood that the specific embodiments described herein are for purposes of illustration only and are not intended to limit the scope of the invention.
Example 1:
a method of sterile production of an aerosol comprising the steps of, in order:
preparation: cleaning the outer packages of the used raw materials, the aerosol cans, the aerosol valves, the valve actuators, the caps and the like, wiping and sterilizing the outer packages with 75% ethanol, and entering a clean area for standby use through an inner package material airlock; the pressure difference between the airlock of the inner packing material and the unpacking of the inner packing material is more than 10Pa;
and (3) raw material treatment: storing propellants of tetrafluoroethane, propane, n-butane and isobutane for 4 hours at the temperature of minus 5 ℃ before filling, and storing the propellants of tetrafluoroethane, propane, n-butane and isobutane for 8 hours at the temperature of 18 ℃ before filling;
preparing liquid: cooling pentafluoropropane to 18 ℃, and then uniformly mixing the pentafluoropropane with quantitative tetrafluoroethane, propane, n-butane and isobutane to obtain a mixed solution, wherein the temperature of the mixed solution is-10 ℃; the temperature between the liquid preparation is 10-28 ℃, the relative humidity is 35-75%, and the relative negative pressure is more than or equal to 5Pa;
raw and auxiliary materials: adding the raw materials and the auxiliary materials into injection water for preparing liquid, and then sterilizing and filtering;
and (3) sterilization: cleaning and drying the aerosol canister, and then performing dry heat sterilization at 170-180 ℃ by adopting a lengthened and widened tunnel oven; an aerosol valve, a valve actuator and a cap which are matched with the aerosol can are sterilized by cobalt 60 irradiation before being assembled;
and (3) filling: filtering the mixed solution and the raw and auxiliary materials by a two-stage 0.22 mu m filter element respectively, and filling the filtered mixed solution and the filtered raw and auxiliary materials into an aerosol can; opening a 100-level laminar flow hood to perform self-cleaning for more than 15 minutes; the mixed liquid and the raw and auxiliary materials are respectively connected with two cartridge filters with 0.22um filter cores in series, and the liquid medicine pipelines are connected. The sterilized aerosol cans are conveyed to a filling production line through a tunnel oven, an aerosol valve, a valve actuator and a cap enter a filling and sealing room through a material purifying program, a sterilizing breathing bag is removed, the aerosol valve is placed into a hopper of an automatic valve feeding device, the valve actuator is placed into a plug feeding hopper, liquid medicine and propellant subjected to sterilization and filtration are respectively filled, the aerosol valve is automatically fed and locked, the valve actuator and the cap are automatically fed, and the aerosol valve is discharged out of the filling and sealing room;
detecting leakage: and (5) detecting leakage of the aerosol can after canning. The leakage detection is to store the aerosol cans for more than 8 hours in the environment of 48-50 ℃ and remove the aerosol cans with large weight errors;
and (5) warehousing: and (5) sticking labels, packaging and warehousing after leakage detection.
Example 2:
a method of sterile production of an aerosol comprising the steps of, in order:
and (3) raw material treatment: storing propellants tetrafluoroethane and propane for 6 hours at 5 ℃ before filling, and storing pentafluoropropane for 12 hours at 28 ℃ before filling;
preparing liquid: cooling pentafluoropropane to 14 ℃, and then uniformly mixing the pentafluoropropane with quantitative tetrafluoroethane and propane to obtain a mixed solution, wherein the temperature of the mixed solution is 8 ℃; the temperature between the liquid preparation is 10-28 ℃, the relative humidity is 35-75%, and the relative negative pressure is more than or equal to 5Pa;
raw and auxiliary materials: adding the raw materials and the auxiliary materials into injection water for preparing liquid, and then sterilizing and filtering;
and (3) sterilization: cleaning and drying the aerosol can, and then performing dry heat sterilization at 170-180 ℃ by adopting a lengthened and widened tunnel oven; an aerosol valve, a valve actuator and a cap which are matched with the aerosol can are sterilized by cobalt 60 irradiation before being assembled;
and (3) filling: filtering the mixed solution and the raw and auxiliary materials by a two-stage 0.22 mu m filter element respectively, and filling the filtered mixed solution and the filtered raw and auxiliary materials into an aerosol can;
detecting leakage: and (5) detecting leakage of the aerosol can after canning. And the leakage detection is to store the aerosol cans for more than 8 hours at the temperature of 48-50 ℃ and remove the aerosol cans with large weight errors.
Example 3:
a method of sterile production of an aerosol comprising the steps of, in order:
and (3) raw material treatment: storing a propellant tetrafluoroethane and n-butane for more than 5 hours at 0 ℃ before filling, and storing pentafluoropropane for 9 hours at 23 ℃ before filling;
preparing liquid: cooling pentafluoropropane to 15 ℃, and then uniformly mixing the pentafluoropropane with quantitative tetrafluoroethane or propane to obtain a mixed solution, wherein the temperature of the mixed solution is 0-2 ℃; the temperature between the liquid preparation is 10-28 ℃, the relative humidity is 35-75%, and the relative negative pressure is more than or equal to 5Pa;
and (3) sterilization: cleaning and drying the aerosol can, and then performing dry heat sterilization at 170-180 ℃ by adopting a lengthened and widened tunnel oven; an aerosol valve, a valve actuator and a cap which are matched with the aerosol can are sterilized by cobalt 60 irradiation before being assembled;
and (3) filling: filtering the mixed solution by a two-stage 0.22 mu m filter element, and filling the filtered mixed solution into an aerosol can;
detecting leakage: and (5) detecting leakage of the aerosol can after canning. And the leakage detection is to store the aerosol cans for 10 hours at the temperature of 18-50 ℃ and remove the aerosol cans with large weight error.
The products are subjected to sterility test, the test is carried out according to the rule of 1101 sterility test method of the fourth edition of the Chinese pharmacopoeia 2015, 10ml of the content is taken and directly inoculated into a culture medium, and the results are shown in the following table.
| Item(s) | Production lot | Number of detections | Detection method | Detection result |
| EXAMPLE 1 sterile aerosol | 20191201 | 120 bottle | Direct inoculation method | No bacteria detection |
| EXAMPLE 2 sterile aerosol | 20191202 | 120 bottle | Direct inoculation method | No bacteria detection |
| EXAMPLE 3 sterile aerosol | 20191203 | 120 bottle | Direct inoculation method | No bacteria detection |
Although the invention has been described herein with reference to a number of illustrative embodiments thereof, it should be understood that numerous other modifications and embodiments can be devised by those skilled in the art that will fall within the scope and spirit of the principles of this disclosure. More specifically, various variations and modifications may be made to the component parts and/or arrangements of the subject combination arrangement within the scope of the disclosure, drawings and claims of this application. In addition to variations and modifications in the component parts and/or arrangements, other uses will be apparent to those skilled in the art.
Claims (5)
1. A method for the aseptic manufacture of an aerosol, characterized by: freezing the propellant into liquid, filtering, sterilizing, and aseptically packaging;
the propellant is at least one of tetrafluoroethane, propane, n-butane, isobutane, chloroethane and pentafluoropropane;
the tetrafluoroethane, propane, n-butane, isobutane and chloroethane are stored for more than 4 hours at the temperature of-5 ℃ before being filled, and the pentafluoropropane is stored for more than 8 hours at the temperature of 18-28 ℃ before being filled;
the preparation method comprises the steps of firstly preparing liquid before filling, wherein the liquid preparation is to cool pentafluoropropane to below 18 ℃, and then uniformly mix the cooled pentafluoropropane with quantitative tetrafluoroethane, propane, n-butane, isobutane or chloroethane to obtain mixed liquid, and the temperature of the mixed liquid is-10 ℃;
filtering the mixed solution by one or more stages of 0.22 mu m filter cores, and filling the filtered mixed solution into an aerosol can.
2. The method for producing an aerosol according to claim 1, wherein the liquid preparation is carried out in a liquid preparation room, the temperature of the liquid preparation room is 10-28 ℃, the relative humidity is 35-75%, and the relative negative pressure is not less than 5Pa.
3. The method for producing the aerosol according to claim 1, further comprising raw and auxiliary materials, wherein the raw and auxiliary materials are sterilized, filtered and filled after being added with injection water for preparing liquid.
4. The method for producing an aerosol according to claim 1, wherein before filling, the aerosol can is cleaned and dried, and then is subjected to dry heat sterilization for 1 hour under the protection of a class-a laminar flow at 170-180 ℃ and 100-class by using a tunnel oven with a length of 3.8-5.2 m and a width of 0.8-1.2 m.
5. A method of aseptic manufacture of an aerosol formulation according to claim 1, wherein the aerosol valve, valve actuator, cap associated with the aerosol canister is sterilized by cobalt 60 irradiation prior to assembly.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010345050.9A CN113636519B (en) | 2020-04-27 | 2020-04-27 | Sterile production method of aerosol |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010345050.9A CN113636519B (en) | 2020-04-27 | 2020-04-27 | Sterile production method of aerosol |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN113636519A CN113636519A (en) | 2021-11-12 |
| CN113636519B true CN113636519B (en) | 2023-07-14 |
Family
ID=78415166
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202010345050.9A Active CN113636519B (en) | 2020-04-27 | 2020-04-27 | Sterile production method of aerosol |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN113636519B (en) |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CH499458A (en) * | 1969-01-03 | 1970-11-30 | Milchwirtschaftliche Forschung | Foam aerosol production |
| CH678514A5 (en) * | 1988-12-22 | 1991-09-30 | Aerosol Service Ag | Free flowing material-dispensing vessel - has sterile inner vessel punctured by discharge valve on first opening |
| CN102626386B (en) * | 2012-04-28 | 2014-10-29 | 山东大学 | Bacilli calmette-gurin polysaccharide nucleic acid inhalation aerosol and preparation method and application thereof |
| CN104490781A (en) * | 2014-12-10 | 2015-04-08 | 广州市香雪制药股份有限公司 | Environment-friendly aerosol and preparation method thereof |
| CN204474302U (en) * | 2014-12-24 | 2015-07-15 | 上海华瑞气雾剂有限公司 | Be applicable to the suspension type MDI two step method bulking system of HFA |
| CN105129706A (en) * | 2015-08-11 | 2015-12-09 | 江苏大红鹰恒顺药业有限公司 | Production technology of sterile oxygen humidification bottles |
| CN205398093U (en) * | 2016-02-29 | 2016-07-27 | 广东泰强化工实业有限公司 | Aerial fog type degreasing agent filling line |
| CN105776114A (en) * | 2016-05-18 | 2016-07-20 | 浙江华艺生物科技股份有限公司 | Preparation method of barbecue edible oil aerosol |
| CN106377519B (en) * | 2016-08-31 | 2019-08-13 | 广东同德药业有限公司 | Anti-inflammatory disinfection removing miliaria and relieving itching aerosol of one kind and preparation method thereof |
| CN110755414A (en) * | 2019-11-12 | 2020-02-07 | 南京华盖制药有限公司 | Arformoterol tartrate aerosol and preparation method thereof |
-
2020
- 2020-04-27 CN CN202010345050.9A patent/CN113636519B/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| CN113636519A (en) | 2021-11-12 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US5749203A (en) | Method of packaging a medical article | |
| CN103491985B (en) | For the sterilizing of medical apparatus and instruments of injecting and/or instil | |
| CN102112374B (en) | Method of examining 'aseptic level of container' in aseptic filling system and the aseptic filling system | |
| CN106829000A (en) | The apparatus and its facial mask preparation method of a kind of sterile filling facial mask | |
| CN106102783B (en) | Sterilization system for a blow/fill/seal machine | |
| CN113636519B (en) | Sterile production method of aerosol | |
| US11466304B2 (en) | System for exposure to a product in the form of an aerosol and method for evaluating the integrity of a container by means of such a system | |
| CN101790974A (en) | Phosphine temperature-controlled fumigating device of fresh and live agricultural product | |
| CN103214805B (en) | Biodegradable barrier-type medicinal packaging bottle and preparation method thereof | |
| CN209039045U (en) | A kind of filtrated air positive Pressure Transportation System for liquid conveying | |
| US3620265A (en) | Method for sterilizing gas containers and filling same with a sterile gas | |
| CN104642512A (en) | Preservation technology of Chinese yam | |
| CN202127740U (en) | Phosphine temperature control fumigating device | |
| CN100368263C (en) | Production of multiple chamber-bags for large infusion for preventing from opening pollution at charging after sterilization | |
| CN210642282U (en) | Solid powder sterilizing equipment | |
| CN111728023A (en) | Litchi low-temperature plasma sterile air-conditioning preservation method | |
| CN107723233B (en) | Equipment and method for producing lactein | |
| Nagarsenkar et al. | Parenteral preparations | |
| CN106115211A (en) | Superheated vapor is to the cooling device for discharging in drug and food powder disinfection system | |
| CN107496968B (en) | Method and system for removing bacteriophage in fermented compressed air | |
| US2862822A (en) | Method for preserving food products in sealed containers of vitreous material | |
| CN104434517A (en) | Double-layer aseptic package, packaging method and sterility test method for large volume injections | |
| Pande | Development and Manufacturing of Injectable (Parenteral) Drug Products | |
| CN207147067U (en) | Freeze dryer with hydrogen peroxide sterilization | |
| US3791424A (en) | Apparatus for sterilizing gas containers and filling same with a sterile gas |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |