Common Preparation Equipment in Pharmaceutical Industry

This article introduces the common preparation equipment in the pharmaceutical industry. It covers liquid preparations, including small injections, large infusions, oral liquids, lyophilized powder injections, and emulsions. The production processes and key equipment for each type of preparation are described.

 

Commonly Used Preparation Equipment

• liquid formulation

Mainstream products of liquid preparations include small injections, I.V. fluids, oral liquids, lyophilized powder injections, emulsions, etc.

1. Small injections and I.V. processes:

1.1 Aseptic preparation: Simply put, it is to dissolve drugs into water for injection (or other solvents) in a certain proportion, and sterilization and filtration to get the final sterile solution. Equipment used by the purified water (for cleaning), water for injection (raw water and final cleaning), pure steam (for equipment, pipeline sterilization), liquid tanks, filters and other equipment.

1.2 Aseptic filling: Filling equipment includes glass bottle filling line, plastic bottle filling line and soft bag filling line, which is the preparation of aseptic medicines through the pipeline closed conveyor to the filling machine, after measurement of the liquid into the container. The glass bottle line includes washing, drying, canning, corking, capping and other processes; the plastic bottle filling line includes blow molding, filling, capping and other processes; the soft bag filling line includes bag making, filling, capping and other processes.

1.3 Cleaning and sterilizing of rubber stopper: mainly for the rubber stopper used in glass bottle filling, the cleaning water is water for injection, and the sterilizing medium is pure steam.

1.4, the final sterilization: at present the most commonly used is the water bath sterilization cabinet, that is, after the canned products are discharged in an orderly manner in the sterilization cabinet, and then the water will be heated to 121 ℃ above the circulation of spray products.

1.5, labeling: that is, labeling, mainly glass bottles, plastic bottles and soft bags using the spray code.

1.6 Packaging: that is, packed inside the carton, small quantities of manual packing, large quantities of similar mechanical arm of the packaging machine.

1.7 Main auxiliary equipment: pulsating vacuum sterilizing cabinet (for sterilizing production apparatus and clean clothes), weighing hood (for weighing solid APIs)

2, oral liquid production process is similar to I.V., only the raw material water with purified water, do not need water for injection, do not need pure steam sterilization.

3, lyophilized powder injection process: powder injection is commonly used penicillin so that, when using the need for sterilized water for injection will be dissolved and then injected, because of the product performance requirements can not be heated and the need for powdered solid preservation.

3.1 Same as 1.1

3.2 Same as 1.2 Mainly used vials, no plastic vials and soft bags, stoppers were not fully pressed in place, leaving some gaps, no capping process.

3.3 Same as 1.3

3.4 Semi-gassing:

3.5 Freeze-drying: the product is discharged in an orderly manner inside the freeze-drying machine box, in a vacuum, low-temperature state of the liquid water in the drug does not go through the solid state directly into a gaseous state, leaving the solid powdered material. Freeze-drying after the end of the box directly in the body of the rubber plug pressure and then out of the box.

3.6 Capping: Use a capping machine to tighten the aluminum cap outside the rubber stopper.

Labeling and packaging as above.

4. Emulsion process flow:

4.1 Oil phase preparation: the main raw material is oil (e.g. soybean oil), add the active ingredient of the drug (generally the drug will not dissolve in water), emulsifiers (e.g. lecithin), and other excipients, so that these materials are dissolved into the oil phase. The equipment used is still a preparation tank, but generally in the tank needs to be used to high-speed dispersion mixing, in order to facilitate the dissolution of lecithin and other materials.

4,2 Aqueous phase preparation: The aqueous phase preparation can be done by using an ordinary dispensing tank to dissolve the water-soluble materials into the water for injection.

4.4 Emulsification: The oil phase material is added proportionally to the water phase, which can be mixed and emulsified proportionally by an in-line emulsifier, or the oil phase material can be added directly to the top of the emulsifier in the emulsifying tank, and the emulsion prepared in this way can only be called colostrum.

4.5 Homogenization: Colostrum is homogenized by homogenizer to refine the milk particles, the homogenization process may take several times until the milk particles are refined to the required degree, in principle, the finer the milk particles the more stable.

Filling and corking processes are the same as above, and the ability to final sterilize depends on the properties of the product.

There are also many oral liquids in the emulsion category, and the process is basically the same, if the requirements are a bit lower to do the colostrum stage (e.g., simethicone oral liquid).

• Paste, Gel

The biggest characteristic of products such as creams and gels is that they have poor fluidity and cannot be sterilized and filtered, and the process of making aseptic preparations is relatively complicated, and the following is a simple explanation of the process of aseptic eye ointment as an example:

1. Melt Oil: Solid petroleum jelly is heated and melted in a melt oil cabinet.
2. Substrate sterilization: melted petroleum jelly is pumped into the sterilization tank, heated by jacketed hot oil to 150°C, held for 1 hour and then cooled to below 80°C and transferred to the preparation tank.
3. For liquid paraffin sterilization, the paraffin is heated in a liquid paraffin sterilization tank by jacketed hot oil to 150°C, held for 1 hour, then cooled and transferred to a premixing tank.
4. Pre-mixing tank in a hundred laminar flow protection of materials (such as Chrysomycin) into the tank, open the tank high-speed disperser will Chrysomycin evenly dispersed into the liquid paraffin, after the end of the dispersion is transferred to the preparation tank and the tank of Vaseline evenly mixed. If the material particles are coarse, we need to use the air flow mill to crush the material to about 10 microns.
5. After mixing, the material is transferred to the temporary storage tank and cooled to below 40℃ before filling.

• CIP/SIP; in-line cleaning and sterilization

In the preparation system will be used in the cleaning and sterilization, poor conditions will be manually carried out, generally will be used in fully automated cleaning and sterilization. The main equipment will be used in the purified water tanks, injection water tanks, detergent tanks and detergent heating devices, transfer pumps and other equipment, but also involves automatic control of the level of the tank, automatic control of temperature, automatic control of the pressure of the water out of the transfer pump and automatic control of the concentration of detergent. Each cleaning is carried out at the set temperature, pressure and concentration, and the repeatability of the cleaning results is very good. Sterilization is controlled by program to control the temperature and time of each point.

• Automatic control:

In addition to the realization of automatic control to meet the requirements of the operation of the equipment, there is a security are very important:

4.1 Three levels of password login operation, which is the most basic, respectively, for the visit level, operator level, administrator level (called a lot of), the visit level can only browse the equipment running screen, can not carry out any operation; operator level can be turned on and off, convert the page, view the contents of the alarm, print the operating parameters and other simple operations. The administrator level can perform simple operations such as opening and closing, switching pages, viewing alarms, printing operating parameters, etc. The administrator level can perform operations such as process grouping, modifying parameters (some parameters need to be authorized by the quality manager).

4.2 Electronic Records and Audit Trail: This is a higher demand, generally need to audit the EU will need, with this feature there is a strong traceability, such as to check a batch of product production, can find out who is the operator, he logged on to do what the operation, the process parameters, and even find out when which valves are open and so on.

4.3 Other backup measures and security, power outages, emergency management measures, etc. belong to the category of computer verification, these general customers have the ability to solve their own, not the ability to mention.

V. Suppliers

         5.1 EVERHEAL can solve water treatment equipment, liquid mixing equipment, and automatic control systems.
         5.2 For filling equipment, Chutian Technology is well-known, and Taizhou Xinya Di also has many users.
         5.3 Most of the filling machines for eye ointments, gels, etc. use Shanghai Longteng.
         5.4 Shandong Xinhua is the leader in sterilization cabinets, and there are also many other brands, such as  Qianying and           Jiangsu Shennong.
         5.5 Dongfulong is the leader in lyophilizers, and other brands are not commonly seen in the market.
         5.6 Shanghai Shenlu has many users for domestic homogenizers.
         5.7 For in-tank emulsifiers, imported ones include IKA, semi-imported ones include Shanghai Fluko, and domestic ones           include Wenzhou Xingsheng and Wenzhou Boao.
          5.7 Pipeline emulsifiers include Shanghai EKen and Wenzhou Xingsheng.