Powder Mixing PDF

# Powder Mixing ## Objectives of Dry Powder Mixing * For preparation of multidose dry powder, for exapmle effervescent salt or antacids. The constituent must be well-mixed to give uniform dose. * Mixing of ingredients before compressing as tablets or filled in capsules. ## Ideal vs. Practical Mi...

# Powder Mixing ## Objectives of Dry Powder Mixing * For preparation of multidose dry powder, for exapmle effervescent salt or antacids. The constituent must be well-mixed to give uniform dose. * Mixing of ingredients before compressing as tablets or filled in capsules. ## Ideal vs. Practical Mixing * In powder mixing, achieving an ideally uniform or "perfect" mixture is **extremely challenging**. * This is because every particle type needs to be evenly distributed throughout the blend. * Instead, the focus is usually on a **"random mix"**. * In a random mix the probability of encountering a specific type of particle matches that particle's overall proportion in the mixture. * This is an acceptable approximation that provides a reasonably consistent distribution. ## Mechanisms of Powder Mixing - **Convective mixing**: Similar to bulk transport in fluids, it is an efficient mixing mechanism for powders. - **Shearing mixing**: Layers of particles slide over each other creating localized shearing forces that improve particle contact and interaction. This is essential for breaking up clumps and enhancing overall uniformity. - **Diffusive mixing**: Also known as **Dispersion**; random, small-scale movements within the particle beds help to fine-tune the mixture leading to gradual homogenization. ## Illustrative Diagram of Powder Mixing The page contains a diagram illustrating the three types of powder mixing: - **(a) Convection**: Particles move in a circular pattern with arrows indicating their direction of movement. - **(b) Diffusion**: Particles move randomly with arrows indicating their direction of movement. - **(c) Shear**: - **First step**: A shearing surface is shown with particles on either side of it. - **Second step**: Particles are reorganized by convection and diffusion mechanisms illustrated by arrows. ## Mixers for Dry Powder ### Tumbling Mixers - Where the movement of the particles occurs by sliding the material using gravity to induce flow. ### Agitator Mixers - Where shear force is applied by means of agitating force. ## 1- Tumbling Mixers * **Uses gravity** to induce flow of the powder bed. * Operates by **tumbling the material** in a partially filled container rotating about a horizontal axis. * **Rotation of the container** imparts movement of the material. * **Uses mild forces**, suitable for fragile materials but **not** for those that clump strongly. * **The mixing effect is improved by baffles.** * **Asymmetrical shape** causes both sideways movement and tumbling for better blending. ### Types of Tumbling Mixers - Barrel mixer or Drum mixer - Cube mixers - Double cone mixers - Twin-Shell Blender A diagram shows the different types of mixers: - (A) Twin-shell - (B) Cube - (C) Drum The diagram also includes an image of a Twin-Shell Blender with components labeled: - Transmission gear - Reducer - Feeding port - Motor - Bearing housing - Discharge butterfly valve - Frame ### 1- Barrel Mixer or Drum Mixer * The simplest equipment. * Shear forces are low. * Not very efficient. * **Baffles** impose the cross flow and improve mixing. * Inclining the barrel to disrupt the symmetry. A diagram shows side and end views of a Barrel Mixer or Drum Mixer. ### Cube Mixers * It has a flat surfaces and therefore sliding flow rather rolling flow. * Not efficient and induces abrasion of the particles against the wall of the vessels. * Contains dead spots. * Difficult in cleaning due to presence of corners. A picture shows a Cube Mixer. ### Double Cone Mixers * Easily cleaned * Very efficient * It is charged by 50% of its capacity to ensure complete transfer of powder. A diagram shows a Double Cone Mixer with the following components labeled: - Transmission gear - Reducer - Motor - Feeding port - Discharge butterfly valve - Bearing housing - Frame ### Twin-Shell Blender * Popular design shaped like a "V" * Formed by cutting and rejoining a cylinder at an angle. * When rotated, material collects at the bottom of the "V" and splits as it inverts, promoting bulk transport and shear for effective mixing. * Some models have a bar with blades that rotate in the opposite direction for extra agitation. * This can be replaced by a hollow tube to add liquids. A diagram depicting a Twin-Shell Blender with the following components labeled: - Machine frame - Feed inlet - V-shaped mixing cylinder - Feed inlet - Coupling Speed reducer - Feed outlet - Electric motor - Frame base ### Twin-Shell Mixers * The V-shaped blender provides a **non-symmetrical** shape about the axis of rotation. * **Combines** the efficient blending action of inclined barrel with the mixing action that occurs when the two inclined cylinders combine their flow. * The effectiveness of this mixing action makes the twin-shell blender the **fastest** of the precision blenders. ### Twin-Shell Blender Advantages - No dead spots in mixing - Easily cleaned - No corners ## Factors to be considered in operating Tumbling Mixers - **Optimum speed**: Too slow leads to sliding (no good mixing), and high speed leads to centrifugation forces and segregation (no good mixing). - **Not to overcharge the mixer**: Do not exceed 50% of the capacity. - **Loading of the component not side by side**: ## Advantages of Tumbling Mixers * Mild equipment used for friable materials. * They are preferred when different particle sizes and densities are to be mixed. ## 2- Agitator Mixers - **Uses a stationary container** with moving screws, paddles, or blades to mix the material. - **Unlike** tumbling mixers, they do not rely solely on gravity. - **Work well with materials** that are sticky or have been moistened, where particles tend to stick together. * The high shear forces created by the moving parts help to break up lumps and aggregates in the material. ## Ribbon Blender * This mixer is a horizontal cylindrical tank, usually open at the top. * Ribbon blender is a stationary trough type of shell approximately 3 times as long as its width. * It has helical blades or ribbons attached to a horizontal axis. * The blades rotate, circulating the material for mixing. * The helical blades (inner and outer) rotate in opposite directions to move the material along both directions of the tank. * The amount of materials moved by the ribbons is relatively small. * Extended mixing time allows for a well-mixed blend, even when particles vary in size, shape, density, or tend to clump. A diagram of a Ribbon Blender shows: - Helical blades - Mixer shell - Discharge spout - Side view - Drive shaft ## Ribbon Mixing Applications * **The ribbon blender induces grinding action and should not be used for fragile particles.** * Useful for blending particles that tend to aggregate or do not flow freely. * The blender can be jacketed for heating or cooling and can be used for mixing light pastes. ## Ribbon Mixing Disadvantages * Not a precision blender * Power needed is higher compared to tumbling mixer * The blender imposes some grinding action. ## Planetary Mixers - **Planetary Mixing Action**: The mixer's element moves in two ways: it rotates around the container's edge and also around its own axis. - **Benefits**: This double rotation minimizes dead zones and prevents vortex formation, leading to more effective mixing. - These mixers are also used for blending solid-solid materials. - This blending often happens before adding liquids to the mixture. A diagram shows the mixing arm of a planetary mixer. ## 3- Fluidized Air Mixers * As an alternative to mechanical agitators, air movement may be used. * Here the driving force is the compressed air which is introduced through nozzles presents at the lower part of the machine. * The nozzles are arranged to direct the airflow upward, allowing the powder to settle. * The body of the powder is fluidized, and mixing is accomplished by circulation and over tumbling in the bed. ## Practical Considerations - The quality of a mixture is assessed based on the random distribution of its components. - A quantitative method is needed to measure how well the components are mixed, referred to as "goodness of mixing." - This can be achieved via: - Microscopic counting if powder of different shapes - Analytical techniques - Screen analysis (using thieves to separate powders of different particle size) ## Segregation/ Demixing * Mixing different types of powder grains often leads to segregation (demixing). * This is where non-uniform regions form spontaneously. * Segregation occurs due to differences in particle size, density, shape, and other properties. * It can be influenced by gravity or by centrifugal, electrical, or magnetic fields during processing. * Segregation happens both during mixing and when handling the finished mixture. ## Factors Affecting Powder Segregation - Particle size - Particle density - Particle charge - Particle proportion ## 1- Particle Size * **Particle Size Difference**: The main cause of segregation in powder mixes is the difference in particle sizes. * **Smaller particles** fall through the gaps between larger particles, settling at the bottom. * **Larger particles** have more kinetic energy and can move farther during mixing, leading to separation based on size. * **Very small particles (dust)** can be lifted by turbulent air currents and remain suspended during mixing. * Once mixing stops, these small particles settle and form a layer on top of the larger particles, this is known as elutriation segregation, fluidization segregation, or dusting out. ## Strategies To Reduce Segregation - **Allow the mixer to rotate slowly (to avoid dusting out)** - **Reduce the particle size variability via:** - **Sieve Selection**: Choose specific size fractions by sieving to remove fines or lumps, ensuring drugs and excipients are of similar particle size. - **Milling**: Reduce the particle size range or ensure all particles are below approximately 30 µm to minimize segregation issues. - **Granulation**: Enlarge the powder mix to create granules with a more uniform distribution of different particles, reducing segregation. ## 2- Particle Density * When particles have different densities, **denser particles tend to move downwards**, even if their sizes are similar. * In many pharmaceutical formulations, the components often have similar densities, making density effects less significant. ## Strategies To Reduce Segregation * **Similar Densities**: Selecting excipients (inactive ingredients) that have densities similar to the active components helps reduce the chances of segregation. * **Particle Size Reduction**: Reducing the particle size of denser components can eliminate the effects of density differences, minimizing segregation. ## 3- Particle Charge - **Surface charges** are formed due to constant friction among the mixed particles. - **Similar charges repel** each other, and opposite charges leads to clump formation. ## Strategies to Reduce Segregation - Stop mixing when obtaining the required mixture – donot extend time. - Add wetting agent or SAA agent. - Add little of water and remove it by evaporation after mixing. ## 4- Proportions of the Materials * The mixing of equal numbers of particles, of two substances represents the best mixing conditions for mixing. * Geometric dilution mixing is recommended. ## Scale of Scrutiny * **This term refers to the smallest region that can reveal imperfections in the mixture.** * It can be measured in terms of length, area, volume, or weight. * **Samples must be large enough to include enough particles for an accurate representation of that region but not so large that they mask small variations in composition.** * The scale of scrutiny varies based on the intended use of the mixture. For example, if the product is a tablet, the scale of scrutiny would be the weight of a single tablet. ## Sampling Techniques * The method of sampling is more critical than the degree of mixing for analysis. * Samples can be taken during the discharge of the mixture or directly from the mixer. * A common sampling tool is a "thief," which consists of two concentric tubes. * The sampling tool and technique should avoid further mixing or inducing demixing of the materials.