Blending/Mixing of Solid Dosage Forms
Loyd V. Allen, Jr., PhD, RPh
Very few medications are pure substances; most are mixtures. Mixtures are generally either solids, liquids, semisolids, and, in some cases, gases. Mixing is a unit operation involving the manipulation of a heterogeneous physical system with the goal of making it homogeneous. This brief presentation will cover mixtures of solids and how they become "mixtures" via mixing, or blending.
When two or more powdered substances are to be combined to form a "uniform" mixture, one must be aware of the characteristics of powders that affect blending, as follows:
Generally, particles of uniform size are blended easier. One can visualize a mixture of large and small marbles and the difficulty involved in blending as the smaller marbles in this case tend to sink pushing the larger marbles to the surface. This is visually evident when baking if one takes a substance such as flour and shakes it back and forth and the larger particles rise to the surface.
Spherical particles tend to be easier to mix, as they will be transported more easily from areas of high concentration to lower concentrations. Needle-shaped particles and cubic-shaped particles do not slide over each other as easily and tend to clog or stick together.
Higher density, or heavier, particles tend to sink, and less dense, or lighter, particles tend to rise. Consequently, when blending particles of different densities, care must be taken to ensure uniformity of mixing.
Static electricity tends to hamper blending and needs to be addressed. This can often be overcome by humidification of the work area or the inclusion (if appropriate) of a small quantity of sodium lauryl sulfate or similar material to neutralize the charges.
By their nature, some particles may tend to either adhere or repel each other, and the faster they are individually diluted with an inert substance or nonreactive material in the formulation, the easier to blend.
Some substances, such as camphor, are slightly gummy in nature and need to be reduced in particle size (pulverization by intervention) and immediately mixed with an inert material in the formulation to aid in the overall blending process.
Powders are generally blended for compounding by spatulation, trituration, sifting, and tumbling. Since most should be familiar with the first three methods, we will only discuss some tumbling methods and resonant acoustic mixing using laboratory-/compounding-scale blenders.
This method involves tumbling the powders in a rotating chamber designed to enhance the mixing process. Mixing by this process is thorough but can be time consuming. However, it can be done while performing other duties. The speed of the rotating chamber is such that the powders "tumble" over and over and do not simply slide down the side of the chamber. This type of blender is very widely used in industry on a large scale.
Triple V-Type Blender
This V-blender consists of three individual chambers attached to the blender power unit and allows up to three different blending processes to be conducted simultaneously.
This blender is used to obtain a homogeneous mixing of powders with different specific weights and particle sizes. The powders can be mixed in their own closed container. The efficiency of this shaker-mixer is derived from the use of rotation, translation, and inversion, according to the Schatz geometric theory. The mixing container is subjected to a three-dimensional movement that exposes the product to a continuously changing, rhythmically pulsing motion.
Resonant Acoustic Mixer
The Resonant Acoustic mixing technology uses low-frequency, high-intensity acoustic energy to create a uniform shear field throughout the entire mixing vessel, resulting in rapid fluidization (movement) and dispersion of the material. An oscillating mechanical driver creates motion in the mechanical system, which is then acoustically transferred to the material to be mixed; the system operates at resonance and, in this mode, there is a nearly complete exchange of energy between the mass elements and the spring elements in the mechanical system.
Tumbling devices have numerous advantages. They are relatively easy to use, and the containers can, in some cases, be the ultimate dispensing container. These units revolve at about 40 rpm, which is about half the critical speed where the centrifugal force on the particles exceeds the pull of gravity so there are not complex controls with which to adjust, etc. They do occupy approximately 4 to 9 square feet of space on a workbench, but the benefits are many. The technology continues to evolve to produce uniform, homogenous mixtures of powders for dispensing or for additional processing.