Mixing & Homogenization Lecture 1 PDF

# Mixing & Homogenization ## Applications - Granules - Tablets - Capsules - Compounds ## Mixing "The process in which two or more than two components in a separate or roughly, mixed conditions is treated in such a way that each particle of anyone ingredient lies as nearly as possible to the adjac...

# Mixing & Homogenization ## Applications - Granules - Tablets - Capsules - Compounds ## Mixing "The process in which two or more than two components in a separate or roughly, mixed conditions is treated in such a way that each particle of anyone ingredient lies as nearly as possible to the adjacent particles of other ingredients is called mixing." ### Objectives of Mixing - To ensure uniformity of composition between mixed ingredients. - To initiate or enhance physical or chemical reactions e.g. diffusion and dissolution. - To improve single phase and multiple phase system. - To control heat and mass transfer. ### Results of Mixing - When two or more than two miscible liquids are mixed true solutions are obtained. - When two immiscible liquids are mixed in the presence of emulsifying agent, emulsions are produced. - When a solid is mixed in a vehicle a solution is obtained. - When an insoluble solid is mixed in a vehicle a suspension is obtained. - When a solid/liquid is mixed in a semisolid base/ointment suppositories are produced. - When two or more than two solids are mixed together a solid dosage form is obtained. ## Types of Mixtures 1. **Positive Mixtures** - Spontaneous, irreversible and complete mixing of two or gases or miscible liquids through diffusion, without the ex energy results in a positive mixture. 2. **Negative Mixtures** - These are formed when insoluble solids are mixed with a vehicle to for a suspension or when two immiscible liquids are mixed to form emulsion. - These mixers require a high degree of mixing with external force. 3. **Neutral Mixtures** - The components of neutral mixers do not have the tendency to mix spontaneously but once mixed, they do not separate out immediately e.g. ointments, pastes. - Neither mixing nor de-mixing unless system is acted upon by an external energy input. ## Degree of Mixing - Degree of mixing is defined in terms of standard deviation: - Standard deviation = $\sqrt{\frac{xy}{N}}$ - Here, - *x* and *y* are proportions of the major and minor constituents, *N* is the number of particles in the sample taken. - Mixing of powder should be continued until the amount of active drug that is required in a dose is with in  ± 35° of that found by assay in a representative number of sample doses. ## Mechanism of Mixing - In all type of mixers mixing is achieved by applying one or more of the following mechanisms: 1. **Convective Mixing** - During convective mixing, transfer of groups of particles in bulk take place from one part of the powder bed to another. 2. **Shear Mixing** - During shear mixing, shear forces are created within the mass of the material by using agitator arm or a blast of air. 3. **Diffusive Mixing** - During this mixing, the material are tilted so that the gravitational forces causes the upper layers to slip and diffusion of the individual particles take place over newly developed surfaces. Mixing occur by diffusion process by random movement of particle within a powder bed and cause them to change their relative position. ## Classification of Mixing Equipments ### Powder Mixers / Solid Mixers 1. Pestle and Mortar 2. Spatula 3. Sieves 4. Tumbler Mixers - a) Cube Mixers - b) V Mixers - c) Double Cone/H type - d) Y Mixers 5. Agitator Mixers - a) The Ribbon Blender - b) Helical Flight Mixer - c) Monastery Blender - d) Paddle Mixer - e) Granulating Mixer - f) Trough Mixer ## Factors Affecting Powder Mixing ### Mixing Factors - Powder mixing operation is quite different from that of liquid. Following factors must be considered: - **A. Volume** - Sufficient space should be provided during mixing for dilation of the bed overfilling of the mixer reduces the efficiency of mixing. The mixer should not be full to the brim. - **B. Mixing Mechanism** - The mixer selected for mixing must apply suitable shear forces and convective movement so that the whole of the material passes through the mixing area. - **C. Duration of Mixing** - Mixing of powders must be done for optimum time for any particular situation. - **D. Handling of Mixed Powders** - After mixing the powders, they should be handled in such a way that the separation of ingredients in minimized. ### Physical Properties/Factors - **A. Material Density** - If the density of mixing ingredients is different, the denser material will sink through the lighter one forming a layer at the bottom resulting in improper mixing. - **B. Particle Size** - Variation in particle size can lead to segregation since smaller particles can fall through the voids between the larger particles. - **C. Particle Shape** - Spherical shape of particle is ideal for mixing the powders and any deviation from this shape leads to difficulty in mixing. However, once the mixing has been done, the particles with irregular shapes can interlock with each other, reducing the chance of segregation. - **D. Particle Attraction** - Some particles exert electrostatic charges due to which the particles of one powder may attract to particles of another powder leading to aggregation of particles. - **E. Proportion of the Materials to Be Mixed** - It is easy to mix powders if they are available in equal quantities but it is difficult to mix small quantities of powders with large quantities of other ingredients or diluents. ## Equipments for Powders Mixing 1. **Pestle and Mortar** - It is the most commonly used equipment for small scale mixing, especially in compounding prescriptions. In this method, particle size reduction and mixing is done in a single operation. 2. **Spatula** - This method is relatively insufficient but is used when compaction produced by pestle and mortar method is undesirable. 3. **Sieves** - Sieves are generally used for breaking the loose aggregates of powders in pre or post mixing operation so as to increase overall effectiveness of a blending technique. Sometimes powder may have to be passed a number of times through the sieve to get a homogenous powder. 4. **Tumbler Mixer (Blender)** - These mixers are used for large scale mixing or batch mixing of powders. The efficiency of tumbling mixer is highly dependent on the speed of rotation. Rotation that is too slow that does not produce the desired intense tumbling or cascading motion nor does it generate rapid shear rates. The rotation that is too rapid tends to produce centrifugal force.