When making medicine in the pharma industry, mixing is always needed. It combines two or more powdered substances to achieve a uniform and homogeneous mixture. This makes APIs and excipients blend evenly.
So consistent drug formulation and good product quality could be ensured.
Whether making capsules or tablets, you have to understand mixing well for production. Here are some key information you should know.
- What are the three types of powder mixing?
- What are the methods of mixing for small-scale business?
- Which factor influences powder mixing in real practice?
Three Common Methods Used in Industrial Pharma Manufacturing
For mass production in the factory, there are 3 popular techniques to be used for mixing.
Diffusive mixing
It means that powder particles move randomly and mix through individual particle motion. This type of mixing relies on the natural movement of particles. It is often generated by external forces such as rotation or vibration. In pharmaceutical manufacturing, diffusive mixing is commonly used in tumbling mixers, such as double-cone blenders. As the mixing equipment rotates, the powders fall and slide over each other. It leads to gradual blending over time.
Diffusive mixing features a slow but gentle process. Thus, it is suitable for fragile or free-flowing powders. The risk of breaking or damaging delicate powder particles is minimal.
However, its mixing efficiency depends on factors such as rotation speed, mixing time, and powder properties. If the speed is too high, it may cause segregation instead of uniform blending. If the speed is too low, mixing may take a longer time to reach homogeneity.
Another major challenge of this method is the potential for segregation. It usually occurs when handling powders with different densities and particle sizes. To overcome this issue, manufacturers use flow enhancers for uniform blending. Despite its limitations, diffusive mixing is still an essential method for pharmaceutical powder blending.
Convective mixing
Convective mixing involves the bulk movement of powder particles. This transports powder from one area to another rapidly. It is more efficient than diffusive mixing. In pharmaceutical manufacturing, many machines can conduct convective mixing, such as ribbon blenders, paddle mixers, and high-speed agitators. These machines use rotating blades or paddles to continuously move powders in different directions. This prevents stagnation and improves blending efficiency.
This blending method features high speed and great suitability for large-scale production. This makes it ideal for blending large batches of pharmaceutical powders, such as granulation blends, bulk API formulations, etc.
However, convective mixing may not be suitable for fragile or heat-sensitive powders. Because excessive shear forces could change particle properties. In addition, if you deal with powders with poor flow characteristics, pre-treatment is required. Manufacturers always use granulation to improve ingredient properties.
Shear mixing
Shear mixing is a high-intensity mixing process. During mixing, powders are mixed with strong shear forces to achieve uniform blending. Shear mixing applies mechanical force to break powder balls for fine dispersion. This method is commonly used in high-shear mixers. They are equipped with rotating blades that create intense shear stress.
Moreover, this mixing method is designed to handle cohesive and poorly flowing powders. Many powders would form agglomerates due to static charges or moisture. Shear mixing effectively solves this problem to achieve precise mixing. So shear mixing is widely used in wet granulation, direct compression blends, and powder coatings to make tablets.
But it also has disadvantages. A higher shear force can generate a certain amount of heat. It may cause API degradation or unwanted phase transitions, especially for heat-sensitive ingredients. Moreover, excessive shear forces may lead to over-mixing. This could affect powder flowability and compressibility.
Five Popular Mixing Types for Laboratory or Small-Scale Operation
In pharmaceutical laboratories or small-scale production, different manual or semi-manual mixing techniques are used. These methods are particularly useful for small-batch preparation, formulation trials, and compounding in pharmacies. Here are some common examples.
Trituration
This method needs a mortar and pestle to blend powders. The powders are placed in a mortar, and a pestle is used to apply pressure and circular motions to break down larger particles and mix them. This method not only ensures proper blending but also helps in reducing particle size. Many operators use it to mix potent drugs.
Trituration is simple and cost-effective, but it requires more time and energy. In addition, this mixing type is not suitable for powders that are hygroscopic or tend to degradation from mechanical force.
Spatulation
Spatulation requires a spatula to blend powders on a smooth slab or containers like bowls. This process continues until the mixture appears uniform. Spatulation is particularly useful for mixing lightweight and non-cohesive powders. Workers in drug stores usually use it to mix dermatological powders, such as ointment bases.
But please note that this method is not effective for cohesive or electrostatic powders. It may not mix well without additional force.
Tumbling
Tumbling mixing is a low-energy mixing method. It relies on the slow rotation of a container. This allows powders to fall and roll over under gravity. Then it gradually achieves a uniform blend. The rotating speed could be adjusted. This technique is commonly used in machines like V-blenders and double-cone blenders.
Tumbling is suitable for fragile powders because of its gentle motion. And it generates minimal heat, reducing the risk of API degradation. Though this method costs less energy, the mixing time is longer. Moreover, it may cause segregation if powders have significant differences in particle size or density.
Sifting
In the sifting process, powders pass through a fine mesh screen to achieve uniform blending. Any lumps, oversized particles, or foreign materials are separated. Then a uniform blend is achieved. Sifting is often used for pre-mixing raw materials. It is effective for breaking powder agglomerates to improve flow properties. It also removes impurities or oversized particles for better product quality.
However, this method is not ideal for cohesive powders. They may clog the sieve during mixing. It also cannot achieve deep mixing, especially for large quantities or dense powders.
Geometric mixing
This is a stepwise geometric dilution mixing technique. During mixing, a small amount of API is first blended with an equal amount of an excipient, such as lactose. Once evenly mixed, the mixture is combined with an equal amount of excipient again. Then mix them evenly.
Repeat this process until all the powders are uniformly distributed. This technique is popular because it prevents the API from being unevenly dispersed in a large amount of excipients. It is usually used in formulations with potent drugs, such as hormones.
What Influences the Effectiveness of Powder Mixing?
Particle properties
Particle sizes need to be considered at first. Powders with similar sizes mix more easily. Large differences in size can lead to segregation. Then you should consider particle shape. Spherical particles mix better and flow smoothly. Irregular or needle-shaped particles may cause uneven distribution and poor flow.
Another factor is particle density. Powders with different densities may separate after mixing. When it comes to low-density powders, they may remain suspended longer.
Environment factors
Before mixing, your powders must be kept in a dry place. Some powders are easy to absorb moisture, leading to clumping and poor flowability. Moreover, high humidity can cause powders to stick to mixing equipment. It greatly impacts mixing efficiency and quality. You should also notice the temperature. Excess heat may lead to the degradation of heat-sensitive APIs.
The End
There are many mixing techniques to choose from. You should select the most suitable one based on your material properties. If you need mixing machines, Huada Pharma is a good partner. We offer different types of mixing equipment to meet various needs. We also have a professional team to give you useful instructions for machine maintenance, troubleshooting, staff training, etc.