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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   Abstract 

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 2014 Jul 30];2:216-20. Available from: http://www.asiapharmaceutics.info/text.asp?2008/2/4/216/45033



   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

1.Abouzeid AZ. Processing of fine particles in mineral beneficiation. Part 1. Powder Handling and Processing 1994;6:35-48.  Back to cited text no. 1    
2.Price M. Size reduction. In: Othmer K, editor. Encyclopedia of chemical technology. New York: John Wiley and Sons; 1999. p. 836-8.   Back to cited text no. 2    
3.Rudd DF, Powers GJ, Siirola JJ. ′Process synthesis′. Englewood Cliffs, N.J.: Prentice-Hall; 1973, 205-208,   Back to cited text no. 3    
4.Subramanyam CV. ′Size reduction′. In: Pharmaceutical Engineering. 1st ed. Vallabh Prakashan; 2004. p. 144-76.  Back to cited text no. 4    
5.Jani GK. ′Size Reduction′. In: Pharmaceutical Engineering-II. 2nd ed. B.S. Shah Prakashan; 2005. p. 1-30.  Back to cited text no. 5    
6.Parrot EL. ′Milling′ In: Lachman L, editor. The Theory and practice of Industrial Pharmacy. 3rd ed. Varghese Publisher Housing; 1990. p. 21-46.  Back to cited text no. 6    
7.Parrot EL. ′Size Reduction′. In: Swwbrick J, Boyalan JC, editors. ′Encyclopedia of Pharmaceutical Technology′. New York: Marcel Dekker Inc; 1998. p. 101-20.  Back to cited text no. 7    
8.O′Connor RE, Schwartz JB, ′Powder′. In: Gennaro AR, editor. Remington: The science and practice of pharmacy. USA: Lippincott Williams and Wilkins; 2001. p. 681-99.  Back to cited text no. 8    
9.Staniforth J. ′Size Reduction′. In: Aulton ME, editor. The Science of Dosage Form Design. London: Churchill Livingstone; 2nd ed. 2005. p. 166-73.  Back to cited text no. 9    
10.Cooper and Gun. ′Size Reduction′. In: Carter SJ, editor. Tutorial Pharmacy. 6th ed. 2000. p. 183-91.  Back to cited text no. 10    
11.Bond FC. Chemical Engineering. 1952. p. 59-169.  Back to cited text no. 11    
12.Snow RH, Kaye BH, Capes CE, Srety GC. ′Size reduction and size enlargement′. In: Perry RH, Green D, editors. Chemical Engineers Handbook. McGraw Hill International; 1963. p. 1-72.  Back to cited text no. 12    
13.Othmer K. Encyclopedia of chemical technology. New York: John Wiley and Sons; 2002. p. 18,336.  Back to cited text no. 13    
14.Berry CE. Modern machines for dry size reduction in fine size range. Indian Eng Chem 1946;38:672.  Back to cited text no. 14    
15.Banga S, Chawla G, Bansal AK. New trends in the crystallisation of active pharmaceutical ingredients, Business briefing. Pharmagenerics 2004;6:70-4.   Back to cited text no. 15    
16.Crystallization process using ultrasound. United States Patent 20020031577.  Back to cited text no. 16    
17.Kakumanu VK, Bansal AK. Supercritical fluid technology in pharmaceutical research. Businessbriefing: Labtech; 2004. p. 71-3.  Back to cited text no. 17    
18.Pasquali I, Bettini R, Giordano F. Solid-state chemistry and particle engineering with supercritical fluids in pharmaceutics. Eur J Pharm Sci 2006;27:299-310.  Back to cited text no. 18  [PUBMED]  [FULLTEXT]
19.Karanth H, Shenoy VS, Murthy RR. Industrially feasible alternative approaches in the manufacture of solid dispersions: A technical report. AAPS PharmSciTech 2006;7:87.  Back to cited text no. 19  [PUBMED]  [FULLTEXT]
20.Spray drying From Wikipedia, the free encyclopedia. Available from: http://en.wikipedia.org. 08/03/2008.  Back to cited text no. 20    
21.Kawashima Y, Saito M, Takenaka H. Improvement of solubility and dissolution rate of poorly water-soluble salicylic acid by a spray-drying technique. J Pharm Pharmacol 1975;27:1-5.  Back to cited text no. 21  [PUBMED]  
22.Shinde AJ. Solubilization of poorly soluble drugs: A review. Available from: http://www.pharmainfo.net/reviews/solubilization-poorly-soluble-drugs-review. 11/05/2008.  Back to cited text no. 22    
23.Micronization, Micron Technologies, Kent United Kingdom. Available from: http://www.microntech.com/micron/index.html. 14/04/2008.  Back to cited text no. 23    
24.Gran-U-Lizer™ Technology, Modern Process Equipment Corporation, Chicago, llinois 60623 U.S.A. Available from: http://www.mpechicago.com/pharm/. 08/04/2008.  Back to cited text no. 24    
25.Jet-O-Mizer™ Technology, Fluid Energy Processing and Equipment Company, Telford, PA 18969. Available from: http://www.fluidenergype.com/lit.htm. 12/04/2008.  Back to cited text no. 25    
26.Microfluidics. Available from: http://www.microfluidicscorp.com/index.php?option=com_contentandtask=viewandid=20andItemid=39. 10/04/2008.  Back to cited text no. 26    
27.Verheezen JJ, van der Voort Maarschalk K, Faassen F, Vromans H. Milling of agglomerates in an impact mill. Int J Pharm 2004;278:165-72.  Back to cited text no. 27  [PUBMED]  [FULLTEXT]
28.Airaksinen S, Antikainen O, Rantanen J, Yliruusi J. Advanced testing of granule friability determined from size reduction data. Drugs Made in Germany 2000;43:96-9.   Back to cited text no. 28    
29.Mishra BK, Thornton C. Impact breakage of particle agglomerates. Int J Miner Process 2001;61:225-39.  Back to cited text no. 29    
30.Narayanan S. ′Single particle breakage tests: A review of principles and applications to commination modeling′. Bull Proc AIMM 1986;291(4):49-58.   Back to cited text no. 30    
31.Vogel L, Peukert W. Characterization of grinding relevant particle properties by inverting a population balance model. 2002;19:149-57.  Back to cited text no. 31    
32.Hite M, Turner S. Oral Delivery of Poorly Soluble Drugs 400, Pharmaceutical Manufacturing and Packing Source Summer ′03 issue. Samedan Ltd; 2003.  Back to cited text no. 32    
33.Larran JM. Micronisation of pharmaceutical powders for use in inhalation. Pharmaceutical Manufacturing and Packing. Sourcer Spring′05 Issue, 2005.  Back to cited text no. 33    
34.Young L. Stable micro systems, Handling the powder flow problem. Available from: http://www.pharma-mag.com. March 2007.  Back to cited text no. 34    
35.Tservistas M, Levy MS, Lo-Yim MY, O′Kennedy RD, York P, Humphrey GO, et al . The formation of plasmid dna loaded pharmaceutical powders using supercritical fluid technology. Biotechnol Bioeng 2001;72:12-8.  Back to cited text no. 35  [PUBMED]  [FULLTEXT]
36.Tservistas M, Scheper T, Freitag R. Supercritical fluid extraction (SFE)-Novel strategies in the processing of biomaterials. In: Grabley S, Thiericke R, editors. Drug discovery from nature. Berlin: Springer Verlag; 1999. p. 106-13.  Back to cited text no. 36    
37.Sarkari M, Darrat I, Knutson BL. Generation of microparticles using CO2 and CO2 -Philic Antisolvents. Am Inst Chem Eng J (AIChE) 2000;46:1850-9.  Back to cited text no. 37    
38.Kipp JE. The role of solid nanoparticle technology in the parenteral delivery of poorly water-soluble drugs. Int J Pharm 2004;284:109-22.  Back to cited text no. 38  [PUBMED]  [FULLTEXT]
39.Violante MR, Fischer HW. Method for making uniformly sized particles from water-insoluble organic compounds. 1989, US Patent 4,826,689 (May 2).  Back to cited text no. 39    
40.Chattopadhyay P, Gupta RB. Protein nanoparticles formation by supercritical antisolvent with enhanced mass transfer. Am Inst Chem Eng J (AIChE) 2002;48:235-44.  Back to cited text no. 40    
41.Nanosuspension drug delivery Technology and application - Nanotech - Express Pharma Pulse. Available from: http://www.expresspharmapulse.com. 24/02/2005.  Back to cited text no. 41    
42.Aulton ME. Pharmaceutics, The science of dosage form design. 2nd ed. London: Churchill Livingstone; 2002. p. 113-38, 234-52.  Back to cited text no. 42    
43.Pinnamaneni S, Das NG, Das SK. Formulation approaches for orally administered poorly soluble drugs. Pharmazie 2002;57:291-300.  Back to cited text no. 43  [PUBMED]  

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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
India
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DOI: 10.4103/0973-8398.45033

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    Figures

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    Tables

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

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