Asian Journal of Pharmaceutics
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Year : 2008  |  Volume : 2  |  Issue : 4  |  Page : 216-220
An overview of size reduction technologies in the field of pharmaceutical manufacturing

Department of Pharmaceutics, Ganpat University, S. K. Patel College of Pharmaceutical Education and Research, Kherva, Mehsana, Gujarat, India

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Size reduction is a process of reducing large solid unit masses into small unit masses, coarse particles or fine particles. Size reduction process is also termed as comminution or diminution or pulverizations . In addition to the standard adjustments of the milling process (i.e., speed, screen size, design of rotor, load), special techniques of milling may be useful including special atmosphere, temperature control, sonocrystallization, supercritical fluid process. etc. Moreover, some advance technologies of size reduction including Micron Technologies, Gran-U-Lizer™ Technology, Jet-O-Mizer™ and Microfluidics® have been popular. Various application of size reduction concept covers oral delivery of poorly soluble drugs, micronization, nanotechnology (micro- and nano suspensions), etc. This systemic review highlights advantages and disadvantages, mechanisms, theories, techniques, advances, and pharmaceutical applications of size reduction technology.

Keywords: Micronization, milling, particle size, size reduction

How to cite this article:
Patel RP, Baria AH, Patel NA. An overview of size reduction technologies in the field of pharmaceutical manufacturing. Asian J Pharm 2008;2:216-20

How to cite this URL:
Patel RP, Baria AH, Patel NA. An overview of size reduction technologies in the field of pharmaceutical manufacturing. Asian J Pharm [serial online] 2008 [cited 2015 Oct 10];2:216-20. Available from:

   Introduction Top

Size reduction is a process of reducing large solid unit masses (vegetable or chemical substances) into small unit masses, coarse particles or fine particles. [1]

Normally, pharmaceutical powders are polydisperse, i.e., consisting particles of different sizes. Polydisperse powders create considerable difficulties in the production of dosage forms. Particles of monosize (equal size) may be ideal for pharmaceutical purposes. In practice, powders with narrow range of size distribution can obviate the problems in processing them further. Size reduction alone is not sufficient to obtain mono-size or narrow size range powder. Therefore, size reduc­tion and size separation should be combined to obtain powders of desired size. There are numerous industries that depend on size reduction to improve performance or to meet specifications. The chemical, pharmaceutical, food, and mining industries all rely on size reduction. Its uses include grinding polymers for recycling, improving extraction of a valuable constituent from ores, facilitating separation of grain components, boosting the biological availability of medications and producing particles of an appropriate size for a given use. There are many types of size-reduction equipment, which are often developed empirically to handle specific materials and then are applied in other situations. Knowing the properties of the material to be processed is essential. Probably the most important characteristic governing size reduction is hardness because almost all size-reduction techniques involve somehow creating new surface area and this requires adding energy proportional to the bonds holding the feed particles together. Flow properties can be major factors, too, because many size-reduction processes are continuous, but often have choke points at which bridging and flow interruption can occur. [1],[2],[3]

Size reduction process is also termed as comminution or diminution or pulverization. Normally, size reduction may be achieved by two methods, namely precipitation or mechanical process. In the precipitation method, the substance is dissolved in an appro­priate solvent. This method is suitable for the production of raw materials and bulk drugs. Inorganic chemicals, such as calcium carbon­ate, magnesium carbonate, and yellow mercuric oxide, are prepared by precipitation method. In the mechanical process, the substance is subjected to mechanical forces using grinding equipment (ball mill, roller mill, colloid mill, etc.).

Various factors like hardness, toughness, stickiness, slipperiness, moisture content, melting or softening point, abrasiveness, and others (material structure, size, shape, flow, and bulk density of product) ratio of feed size to product size, affect the size reduction [Table 1]. [2],[3],[4]

   Mechanisms of Size Reduction Top

The mechanisms have demonstrated that stresses of varied nature are required to achieve size reduction. The common modes of size reduc­tion are explained as follows [Table 2]:

   Theories of Comminution Top

When various modes of stress are applied on a powder, the particles get strained. This stress-strain relationship is shown in [Figure 1]. [5],[6],[8],[9],[11],[12],[13],[14]

In [Figure 1], the initial linear portion is defined by Hookers law. It states that stress is proportional to strain. The slope of linear portion represents Young's modulus. It expresses the stiffness or softness in megapascals. If the force of impact (stress) does not exceed the elastic limit (region of Hooke's law), the material is reversibly deformed. When the force is removed, the particle returns to original condition. The elastic limit is known as yield value. The stress energy in the deformed particle appears as heat. Example is plastic material such as polymer. The stress-strain curve becomes nonlinear at the yield point. This is a measure of the resistance to permanent deformation. Beyond the yield point, the region represents irreversible plastic deformation. The area under the curve represents the fracture toughness (or modulus of toughness). This is an approximate measure of the impact strength of the material. Fracture of a particle can be obtained when the force exceeds the elastic limit [Table 3].

   Techniques of Milling Top

In addition to the standard adjustments of the milling process (i.e., speed, screen size, design of rotor, load), special techniques of milling may be useful [Table 4]. [6],[15],[16],[17],[18],[19],[20],[21],[22]

   Advances in Size Reduction Technology Top

Micron technologies

Micronizing (defined as particles smaller than 20 µm) often enhances solubility and improves bioavailability, allowing you to optimize the formulation of your product and reduce the therapeutic dose. With a reproducible and controlled particle size of active pharmaceutical ingredients and excipients, manufacturing of finished dosage form could be improved. The most commonly used pieces of equipment are tangential fluid energy mills or pancake mills. High-pressure air/gas is introduced causing particle-to-particle collision and micronization. [23]

Gran-U-Lizer™ technology

Manufacturing Process Equipment's (MPE) high-power Gran-U-Lizer™ size reduction technology is specifically designed to maximize yield and minimize fines in the grinding process. Since each particle passes through each nip once, there is little regrinding of already ground material. This results in a very tight particle size distribution and minimum number of very small particles ("fines"). [24]

A superior particle size distribution with fewer unwanted fines can be obtained for numerous drug products, nutriceuticals, excipients, and cosmetics. It is widely used in numerous dry food grinding mill applications like coffee, flax seed, pepper, rice, salt, sugar, and sweeteners. MPE Gran-U-Lizers are ideal for a multitude of mineral grinding applications where final product yield and a minimization of fines are essential. Typical applications of this technology include activated carbon, coke (metallurgical, petroleum), phenolic resins, super absorbents (SAP).

Jet-O-Mizer™ particle size reduction systems

The Jet-O-Mizer jet mill has been developed with many distinct design features to consume less power, provide a greater range of throughput (1 to 12,000 lb/h) and ensure exceptional finished product quality. Specific raw material characteristics and production requirements are integrated into a Jet-O-Mizer system. It offers outstanding efficiency and versatility in fine grinding (0.5-45 microns) and classification. [25]

Some of the important features of this system are high-efficiency chamber design, adjustable classification zone, no attritional heat, and combined operations (physical or chemical).

It is used for different types of materials like hard, abrasive, sanitary, sterile, heat-sensitive, agricultural, volatile, and synthetic materials.

Microfluidics particle size reduction

Creating a suspension of a solid material generally requires significant reduction of the particle size and the addition of surfactants and other materials to prevent particle agglomeration. The ultrahigh shear developed by the Microfluidizer® processor reduces the particle size of active pharmaceutical ingredients to useful sizes and the high turbulence ensures that the resulting particles are efficiently coated. A major advantage of the Microfluidizer technology is that the processor produces the desired small particles with a narrower size distribution than other methods resulting in a very stable product with a long shelf-life. [26]

When formulating emulsions, especially oil-in-water emulsions for oil-soluble pharmaceuticals; a common objective is that the resulting emulsion be sterilized by filtration. In practical terms, this means that virtually all of the particles in the emulsion are sufficiently small as to not clog the filtration device. Due to the high shear forces available and the flexible design of the Microfluidizer processor, numerous pharmaceutical products have been prepared that permit efficient formation of the emulsion as well as producing a product that can be filter sterilized [Table 5] and [Table 6].

   Conclusion Top

The chemical, pharmaceutical, food, and mining industries all rely on size reduction. Size reduction technology has considerable importance in the pharmaceutical field. It offers several advantages such as content uniformity, uniform flow, facilities mixing, and drying, etc. Moreover, due to advance technologies the concept of size reduction become wider and has application in different field like pharmaceutical manufacturing of novel and conventional dosage forms, drug delivery, supercritical fluid technology, nanotechnology, etc.[43]

   References Top

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Correspondence Address:
Rakesh P Patel
Department of Pharmaceutics and Pharmaceutical Technology, S. K. Patel College of Pharmaceutical Education and Research, Ganpat Vidyanagr, Kherva - 382 711, Mehsasan, Gujarat
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0973-8398.45033

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  [Figure 1]

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]

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