One-time agitation technology in pharmaceutical dosing system, core agitation technology in future biotechnology
June 27, 2018 Source: CPhI Pharmaceutical Online
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Quality stems from design risk stemming from cognition
In the pharmaceutical production process, the pharmaceutical ingredient processing system, online cleaning system and online disinfection/sterilization system are the core components of the entire pharmaceutical production process. Unit operation is the component of the system. In the pharmaceutical production process, the core unit operations mainly include feeding, stirring, mixing, heating, cooling, conveying, centrifuging, extracting, crystallization, filtering, and filling. The mixing technology in the pharmaceutical dosing system is divided into two categories: stainless steel stirring technology and one-time stirring technology.
Stainless steel mixing systems are widely used in metal alloy materials and are used in the pharmaceutical industry to mix homogenized liquids and solids. It can be roughly divided into two kinds of conventional applications: liquid/liquid mixing and solid/liquid mixing. With the passage of time, the stainless steel dosing system has become more and more widely used in the pharmaceutical process, and it has become more and more automated. From the early manual ingredients, semi-automatic ingredients to the current intelligent preparation, the operating volume has increased from a few to several Ten liters can now be as high as tens of thousands of liters or more; the scope of use covers chemical drugs, traditional Chinese medicine and biological products.
Disposable agitation techniques are used in the pharmaceutical field to mix homogenized liquids and solids. It can be roughly divided into three applications: liquid/liquid mixing, solid/liquid mixing and solid/solid mixing. Over time, single-use hybrid systems are increasingly used in aseptic pharmaceutical downstream processes: operating volumes from tens of liters to hundreds of liters, now up to several thousand liters; , protein drugs to vaccines; the process points used are also advanced from the original sterile preparations to the intermediate storage regulation, downstream virus inactivation and other key steps. Because the final dosage form, or the key process point, tends to be closer to the product at the point of application, the integrity of the disposable agitating bag, the release of the particles, and the dissolution of the precipitate are more sensitive.
According to the mixing mode of the disposable mixing system, it can be divided into at least five categories:
1 swing mixing:
The wave mixing system consists of a disposable pillow bag and a rocking platform. The disposable pillow bag is placed on the rocking platform after being filled with liquid, and the liquid is regularly swayed by the rocking platform to form a front and rear or orbital motion, and waves are formed on the surface of the liquid to achieve a mixing effect. The angle and frequency of the sway determine the size and speed at which the waves are generated. The effect of agitation mixing depends on the strength of the sway and the time of mixing. This type of agitation is generally suitable for a liquid/liquid mixing mode.
2 mechanical shaft mixing:
The mechanical shaft mixing is divided into two modes: upper stirring and bottom stirring. They are all rotated or oscillated by a motor-driven mechanical shaft, and the liquid/liquid or solid/liquid is stirred and mixed in a 3D-shaped disposable stirring bag using a paddle or a stirring rod. The 3D agitating bag requires a fixed shape of the container for support (generally cylindrical or cubic) to ensure the shape of the agitating bag and against the water pressure inside the bag. Conventional mechanical on-axis agitation is to install a disposable paddle or stir bar on top of a 3D agitator bag, or to use a reusable paddle/rod, but place them in a closed sleeve of a silicone inner tube to make them Does not come into contact with the liquid. The mechanical agitator paddle is placed at the bottom of the disposable agitating bag. Compared with the upper agitation mode, the bottom agitating system is less restricted by the liquid level of the treated liquid, but the mechanical shaft sealing requirement is relatively high. The stirring effect mainly depends on the shape, size, speed and other comprehensive parameters of the blade. Since it is driven by the motor, the larger the output power is, the better the stirring effect is. It can be used to mix the thick and difficult to mix.
3 magnetic stirring:
The magnetic stirring system is the most common mode for disposable mixing systems. The stirring blade of the bottom of the 3D agitating bag is driven by electromagnetic force to achieve a liquid/liquid or solid/liquid mixing effect. The magnetic stirring system's disposable stirring paddle is built into the mixing bag and can be divided into two categories: magnetic bearing mixing system and magnetic suspension mixing system. The stirring blade of the magnetic bearing stirring system and the bottom of the stirring bag are connected by an inert bearing, and the blade rotates to not contact the inner film of the bag. The magnetic levitation system uses a superconducting drive. Once a stable magnetic field is formed, the stirring paddle is suspended and rotated to stir and mix. The magnetic suspension agitator has no bearings and seals in the bag, so there is no friction between the suspended blade paddle and the bag membrane material or the bearing, and it is recognized as an ultra-clean agitating system. It is mainly used in the key process points of formulation filling. As with mechanical shaft agitation, 3D magnetic mixing bags require a fixed shape container for support. Generally, the support container is cylindrical or cubic. From the perspective of mixing efficiency, the cube's support container can bring better mixing efficiency, because the walls of the cube support container form a natural baffle, which helps to break the laminar flow and expand the mixing range. If the dosing system uses a cylindrical support container, it is recommended to use an eccentric mode for large volume mixing, ie the eccentric position of the paddle at the bottom of the agitator bag.
4 circulating mixing:
The circulating agitation is divided into two types: external circulation stirring and internal circulation stirring (Fig. 1). The outer circulation is that the liquid in the disposable bag is pumped out through the peristaltic pump and circulated into the bag through the external pipeline again, and the effect of mixing is achieved after repeated recycling. Generally only applicable to the mode of liquid/liquid mixing. The inner circulation integrates a magnetically driven turbine in the bottom of the bag. The turbine operates like a centrifugal pump. The liquid inside the paddle bag is vertically drawn down and then discharged through the specially designed outlet along the bottom in a horizontal direction, rushing toward the low angle of the bag. Steering the impact to the top of the bag completes a complete internal loop. The inside of the bag will continue to maintain such a 3D internal circulation until the liquid is evenly mixed.
Figure 1 Circulating mixing
5 vibration mixing and stirring:
The vibrating mixer is typically constructed of a disposable bag with 3D support and a bearing integrated into the interior of the bag and a disc blade having a plurality of tapered perforations on the surface (Fig. 2). Vibration is transmitted through the bearing to the tapered bore of the disc blade to create a Bernoulli effect that causes the liquid to pass up or down through the taper to achieve mixing. This mode of agitation is only suitable for liquid/liquid mixing with low viscosity.
Figure 2 Vibration mixing
Screening of disposable dosing systems needs to be considered from the needs of the process, including the factors listed in Table 1:
Table 1 Process demand factors for screening disposable dosing systems
