Factors affecting mixing: There are factors that can influence the efficiency of mixing, leading to the non-uniform distribution of materials, which can result in inaccurate dosage production. These factors are as follows:
(i) Material density: If the mixture components are of different densities, the denser material will sink through the lighter one, the effect of which will depend on the relative positions of the material in the mixer. To maximize mixing, the denser material is placed at the lower layer in the mixer during the mixing process so as to enhance the degree of mixing to equilibrium state.
(ii) Particle size: Different particle sizes in materials to be mixed can cause segregation that leads to non-uniform distribution. The smaller particles fall within the voids between the larger particles. During the mixing process, the particles in the bed might dilate and the greater porosity of open packing allows a large particle to slip into the void that eventually resulting in non-uniform distribution. As the particle size increases, flow properties also increases due to the influence of gravitational force on the size. It is easier to mix two powders having approximately the same particle size.
(iii) Particle shapes: The particles with spherical shapes are easier to mix uniformly whereas other shape particles face an increase in difficulty in the mixing process. The ideal particle is spherical in shape, and further, the particles depart from this theoretical form, there is greater difficulty of mixing. If the particles are of irregular shapes, then they can become interlocked leading to a decrease in the risk of segregation once mixing has been achieved.
(iv) Particle attraction: Some particles exert attractive forces due to adsorbed liquid films or electrostatic charges on their surfaces and tend to aggregate. Since these are surface properties, the aggregation increases as particle size decreases. The interaction forces between drug and carrier surface are predominately van der Waals’ forces, but electrostatic and capillary forces may also play a role. These forces vary with the size, shape, crystallinity, and hardness of the adhering particle, surface roughness and contamination of the carrier particles, the intensity and duration of
shear forces during mixing and the relative humidity.
(v) Proportion of materials: The proportion of substances in a given mixture is one of the crucial factors that result in the efficacy of mixing. The proportions of materials to be mixed play a very important role in powder mixing. It is easy to mix the 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. However, to ensure uniform mixing, the substance should be mixed in geometric and ascending order of their weights.
(vi) Mixer volume: In mixing process, the mixer must reserve sufficient space for dilation of bed during mixing process. If this condition is maintained the powder samples are getting enough space for the free mixing to achieve uniform mix with increased efficacy. Overfilling reduces the efficiency and may prevent mixing entirely.
(vii) Mixing mechanisms: The suitable and sufficient shear force and a convective movement is prime requirement for the mixer to ensure efficient mixing of bulk material. The mixer selected based on its mechanism must apply suitable shear forces to bring about local mixing as well as convective movement to ensure that
the bulk of the material passes through this area.
(viii) Mixing time: Mixing must be carried out for an appropriate time so that the degree of mixing will approach its limiting equilibrium value. Since, there is an optimum time for mixing of any particular mixture it must be noted that the equilibrium condition may not represent the best mixing if there is segregation. While handling uniformly mixed powders after completion of operation enough care need to be taken to avoid segregation. The vibration caused by subsequent handling, transport or during use is likely to cause segregation.
(ix) Method of handling: When mixing is completed, the product is required to be handled according to standard operating procedures to minimize the risk of segregation. A common factor that causes segregation is vibration throughout the handling, transport, or packaging. This results into fact that all bulk powder should undergo remixing before taking them into use.
(x) Nature of the product: Rough surface of the powder components may result in to ineffective mixing. The active substances which are generally very fine in size may enter into the pores and cavities on the surfaces of the other larger ingredients. If such substances get adsorbed on the surface of other powders there is decrease in aggregation as well as segregation. For example, addition of colloidal silica to strongly aggregating zinc oxide help to maintain fine dusting powder that can be easily mixed.
(xi) Mixing Conditions: The theory of powder mixing shows four conditions that should be observed in the mixing operation. Those conditions affects mixing.