Mixing substances and its mechanism of Pharmaceutical Science

Mixing

Definition: Process that results in randomization of dissimilar particles within a system.

Mechanisms of mixing:
The most common classification of mixers however is based on the type of dosage form they are used to handle. A brief summary of mixing process in relation to the type of dosage form is presented below

1. Mixing for solids
Physical properties that effect the ease of mixing are:
(a) Material density
(b) Particle size and distribution
(c) Wettability
(d) Stickiness
(e) Particle shape / roughness

The most preferred types of mixers for solid mixing are Tumble mixers and Fixed shell mixers. Tumble mixers operate on the principle of bulk transport and shear. The mixing efficiency has a direct co-relation with the speed of rotation of tumble blender. Three types of most commonly used blenders are illustrated below:

A – Double cone blender, B – V blender and C – Bin blender

Fixed shell mixers are equipments in which the material is held in a stationary container and mixing is brought about by means of moving screws, paddles or blades. The ribbon blender consists of a relatively long trough like shell with a semicircular bottom, usually opening at the top and fitted with helical blades. The blades produce a continuous cutting and shuffling of charge by circulating the charged powder from end to end of the trough as well as rotationally.

2. Mixing of liquids
Mixing occurs in two stages:
(a) Localized mixing which applies sufficient shear to the particles of the fluid
(b) A general movement sufficient to take all parts of the material through the shearing zone and to ensure a uniform final product.

Mixing mechanisms fall essentially into four categories:

1. Bulk Transport – movement of a relatively large portion of material being mixed from one location in the system to another.

2. Turbulent flow – Characterized by the fluid having different instantaneous velocities at the same instant of time. The temporal and spatial velocity differences resulting from turbulence produce randomization of fluid particles.

3. Laminar Flow – Streamline flow that is encountered most commonly in highly viscous liquids.

4. Molecular diffusion – Primary mechanism responsible for mixing at the molecular level which results from the thermal motion of molecules.

Governed by Fick's fist law of diffusion,

dm/dt = - DA dc/dx
Where,
dm/dt – rate of transport of mass across a surface area
D – Diffusion Co-efficient
A – Area across which diffusion is occurring
dc/dx – Concentration gradient

Mixing as a process can either be carried batch to batch or can be continuous. Impellers, Air-jets, Fluid-jets and Baffle mixers are the major types of equipment used for batch mixing. Impellers operate using a combination of radial, axial and tangential flow. These might be classified into two further types, Propellers and Turbines, the former being used for low viscosity liquids while the latter for high viscosity ones.

3. Mixing of semi-solids
The mechanisms involved in mixing semi solids depend on the character of the material which may show considerable variation. Many semi solids form neutral mixtures having no tendency to segregate although sedimentation may occur.

Three most commonly used semi solid mixers are

(a)      Sigma blade mixer – Contains two blades which operate in a mixing vessel which has a double trough shape, the blades moving at different speeds towards each other. Used for products like granulation masses and ointments.

(b)      Triple-roller mill – The differential speed and narrow clearance between the roller develop high shear over small volumes of material. The roller mills are generally used to grind and complete the homogeneity of ointments.

(c)       Planetary mixers – it utilizes a mixing arm rotating about its own axis and also about a common axis usually the centre of the mixing wheel. The blades provide the kneading action, while the narrow passage between the blades and the wall of the can provides shear.

Mixer Selection

Factors to be taken into consideration while selecting a mixing equipment include,
(a) Physical properties of materials to be mixed such as density, viscosity and miscibility
(b) Economic considerations – operating efficiency, cost and maintenance

One of the first things to determine is if the process is intended to be a batch or a continuous process, each of which can have its advantages and drawbacks depending on the load to be used. Size is considered keeping in mind the optimal working volume, fill level and residence time. The optimal working volume would depend on the construction of the mixer. It generally lies between 50 to 70 percent of the maximum. Similarly, too much of fill would lead to low mixing and hence fill level becomes important. Residence time which is defined as the amount of time ingredients are in the mixer and is a particularly important determinant of the size of a continuous mixer. Choice of agitators determines the efficiency in breaking up lumps/agglomerates and serves to add shear aiding the final dispersion.

A brief table showing various agitator types and their respective uses in shown below.

1.      Ribbon - For Powders, granules, some slurries, mainly free flowing

2.      Paddle - For Powders, granules, some slurries, free flowing, light pastes

3.      Sigma - For Sticky materials, thick pastes and slurries