`
`Eighteenth Edition
`
`
`
`18rH
`
`EDITION
`
`Remington's
`
`ALFONSO R GENNARO
`Editor, and Chairman
`of the Editorial Doard
`'
`
`
`
`Pharmaceutical
`
`Sciences
`
`1990
`
`MACK PUBLISHING COMPANY
`
`Easton, Pennsylvania 18042
`
`
`
`Entered according to Act of Congress, in the year 1885 by Joseph P Remington,
`in the Office of the Ubrarian of Congress, at Washington DC
`
`Copyright 1889,' 1894, 1905, 1907, 1917, by Joseph P Remington
`
`Copyright 1926, 1936, by Joseph P Remington Estate
`
`Copyright 1948, 1951, by The Philadelphia College of Phnrmacy and Science
`
`Copyright @ 1956, 1960, 1965, 1970, 1975, 1980, 1985, 1990, by The Philadelphia College of
`Pharmacy and Science
`
`All Rights Reserved
`
`L ibrary of Congress Catalog Card No. 60-53334
`
`ISBN 0·912734·04·3
`
`The use of structural formulas from USAN and the USP Dictionary of Drug Names ill by
`permissicm of The USP Convention. The Convention is not responsible for any inaccuracy
`contained herein.
`
`N OTICE-This text is not intended to represent, nor shall it be interpreted to be, the equivalent
`of or a substitute for the official United States Pharmacopeia (USP) and/or the National
`Formulary (NF). In the event of any difference or discrepancy between the current official
`USP or NF standards of strength, quality, purity, packaging and labeling for drugs and
`representations of them herein, the context and effect of the official compendia shall
`preu.ail.
`
`Printed in the United States of America by the Mack Printing Company, Easton, Penn~~yluania
`
`
`
`CHAPTER 88
`
`Powders
`
`Ao.,.rt E O 'Connor. PhD
`/d>iJIOnr Profe$SOI of Phormoc..,lia
`Philadelphia College of Pharmacy ond Science
`Philadelphia. PA 1910.
`
`Edward G 1\lppl•, PhD
`Ptofe-r of Phormoceurk:s
`Collogo of Pharrnocy. Unlvo,lry of Mlnnesoro
`.Minneapolis. MN 55-455
`
`Joa•ph D Schwartz, PhD
`nee Profe.sor of Pharmoc•ullo
`Director of lndustrlol Phorrnoc:y Reworch
`Philadelphia Colt.ge of Phormoc:y ond Sclcnce
`Phltodelphlo. PA 1910.
`
`Powders are encountered in almost every aspect of phar(cid:173)
`macy, both in ,industry and in practice. Drugs and other
`ingrectients, when they occur in the solid state in the course
`of being processed into a dosage form, usually are in a more
`or less fmely divided conctition. Frequently, this is a powder
`whose state of subdivision is critical in determining its be(cid:173)
`havior both during processing and in the fmished dosage
`form. Apart from their use in the manufacture of tablets,
`capsules, suspensions, etc, powders also occur as a pharma(cid:173)
`ceutical dosage form. While the use of powders as a dosage
`form has declined, the properties and behavior of fmely
`divided solid materials are of considerable importance in
`pharmacy.
`This chapter is intended to provide an introduction to the
`fundamentals of powder mechanics and the primary means
`of powder production and handling. The relationships of
`the principles of powd·er behavior to powders as dosage
`forms are discussed.
`
`Production Methods
`
`Molecular Aggregation
`Precipitation and Cr ystaUization- These two process(cid:173)
`es are fundamentally similar and depend on achieving three
`conctitions in succession: a state of supersaturation (super(cid:173)
`cooling in the case of crystallization from a melt), formation
`of nuclei and growth of crystals or amorphous particles.
`Supersaturation can be achieved by evaporation of solvent
`from a solution, cooling of the solution if the solute has a
`positive beat of solution. production of adctitional solute as a
`result of a chemical reaction or a change in the solvent
`medium by addition of various soluble secondary sub(cid:173)
`stances. In the absence of seed crystals, significant super(cid:173)
`saturation is required to initiate the crystallization process
`through formation of nuclei. A nucleus is thought to consist
`of from ten to a few hundred molecules havi.ng the spatial
`arrangement of the crystals that will be grown ultimately
`h:om them.
`Such small particles are shown by the Kelvin equation to
`be more soluble than large crystals and, therefore, to require
`supersaturation, relative to large crystals, for their forma(cid:173)
`tioD and subsequent growth. It is a gross oversimplification
`to assume that, for a concentration gradient of a given value,
`the rate of crystallization is the negative of the rate of ctisso(cid:173)
`lution. The latter is generally somewhat greater.
`Depending on the conctitions of crystallization, it is possi(cid:173)
`ble to control or modify the nature of the crystals obtained.
`When polymorphs exist, careful temperature control and
`seeding with the desired crystal form are often necessary.
`The habit or shape of a given crystal form is often highly
`
`dependent on impurities in solution, pH, rate of stirring, rate
`of cooling and the solvent. Very rapid rates of crystalliza(cid:173)
`tion can result in impurities being included in the crystals by
`entrapment.
`Spray-Drying- Atomization of a solution of one or more
`solids uia a nozzle, spinning disk or other device, followed by
`evaporation of the solvent from the droplets is termed spray(cid:173)
`drying. The nature of the powder that results is a function
`of several variables, including the initial solute concentra(cid:173)
`tion, siz.e distribution of droplets produced and rate of sol(cid:173)
`vent removal. The weight of a given particle is determined
`by the volume of the droplet from which it was derived and
`by the solute concentration. The particles produced are
`aggregates of primary particles consisting of crystals and/or
`amorphous s9lids, depenctiog on the rate and conditions of
`solvent removal. This approach to the powdered state pro(cid:173)
`vides the opportunity to incorporate multiple solid sub(cid:173)
`stances into inctividual particles at a fixed composition, in(cid:173)
`dependent of particle size, and avoiding difficulties that can
`arise in attempting to obtain a uniform mixture of several
`powdered ingredients by other procedures.
`
`Particle-Size Reduction
`Comminution in its broadest sense is the mechanical pro(cid:173)
`cess of reducing the size of particles or aggregates. Thus, it
`embraces a wide variety of operations including cutting,
`chopping, crushing, grinding, milling, micronizing and tritu(cid:173)
`ration, which depend primarily on the type of equipment
`employed. The selection of equipment in turn is deter(cid:173)
`mined by the characteristics of the material, the initial parti(cid:173)
`cle size and the degree of size reduction desired. For exam(cid:173)
`ple, very large particles may require size reduction in stages
`simply because the equipment required to produce the final
`product will not accept the initial feed , as in crushing prior to
`grinding. In the case of vegetable and other fibrous materi(cid:173)
`al, size r eduction generally must be, at least initially, accom(cid:173)
`plis hed by cutting or chopping.
`Chemical substances used in pharmaceuticals, in contrast,
`generally need not be subjected to either crushing or cutting
`operations prior to reduction to the required particle size.
`However, these materials do differ considerably in melting
`point, brittleness, hardness and moisture content, all of
`which affect the ease of particle-size reduction and dictate
`the choice of equipment. The heat generated in t he me(cid:173)
`chanical grinding, in particular, presents problems with ma(cid:173)
`terials which tend to liquefy or stick together and with the
`thermolabile products which may degrade unless the beat is
`dissipated by use of a flowing stream of water or air. The
`desired particle size, shape and size distribution also must be
`considered in the selection of grinding or milling equipment.
`For example, attrition mills tend to produce spheroidal,
`
`1615
`
`
`
`l
`
`1616
`
`CHAPTER 88
`
`more free-flowing particles than do impact-type mills, which
`yield more irregular-shaped particles.
`Fracture Mechanics- Reduction of particle size
`through fracture requires application of mechanical stress to
`the material to be crushed or ground. Materials respond to
`stress by yielding, with consequent generation of strain. De(cid:173)
`pending.on the time course of strain as a function of applied
`stresses, materials can be classified according to their behav(cid:173)
`ior over a continuous spectrum ranging from brittle to plas(cid:173)
`tjc. In the case of a totally brittle substance, complete
`rebound would occur on release of applied stress at stresses
`up to t he yield point, where fracture would occur. In con(cid:173)
`trast, a totally plastic material would not rebound nor would
`it fracture. The vast majority of pharmaceutical solids lie
`somewhere between these extremes and thus possess both
`elastic and viscous properties. Linear and, to a lesser ex(cid:173)
`tent, nonlinear viscoelastic theory has been developed well
`to account for quantitatively and explain the simultaneous
`elastic and viscous deformations produced in solids by ap(cid:173)
`plied stresses. ;
`The energy expended by comminution ultimately appears
`as surface energy associated with newly created particle sur(cid:173)
`faces, internal free energy associated with lattice changes
`and as heat. Most of the energy expressed as heat is con(cid:173)
`sumed in the viscoelastic deformation of particles, friction
`and in imparting kinetic energy to particles. Energy is ex(cid:173)
`changed among these modes and some is, of course, effective
`in producing fracture. It has been estimated that 1% or less
`of the total mechanical energy used is associated with newly
`created surface or with crystal lattice imperfections.
`While the grinding process has been described mathemat(cid:173)
`ically, the tlieory of grinding has not been developed to the
`point where the actual performance of the grinding equip(cid:173)
`ment can be predicted quantitatively. However, three fun(cid:173)
`damentallaws have been advanced:
`
`Kick's Law- The work required to reduce tbe size of a given quantity
`of material is constant for the same reduction ratio regardless of the
`original size of the initial material.
`Ritti.Jiger's Law- The work used for particulate size reduction is
`d.irectly proportional to the new surface produced.
`Bond's Law- The work used to reduce the particle size is proportion(cid:173)
`al to the square root of the diameter of the particles produced.
`
`In general, however, these laws have been useful only in
`providing trends and qualitative information on the grind(cid:173)
`ing process. Usually laboratory testing is required to evalu(cid:173)
`ate the performance of particular equipment. A work index,
`developed from Bond's Law, is a useful way of comparing the
`efficiency of milling operations.1 A grindability index,
`which bas been developed for a number of materials, also can
`be used to evaluate mill performance.2
`A number of other factors also must be considered in
`equipment selection. Abrasion or mill wear is an important
`factor in the grinding of hard materials, particularly in high(cid:173)
`speed, close-clearance equipment (eg, hammer mills). In
`some instances mill wear may be so extensive as to lead to
`highly contaminated products and excessive maintenance
`coets that ma_ke the milling process uneconomical. Hard(cid:173)
`ness of the material, which is often related to abrasiveness,
`also must be considered. This usually is measured on the
`Mob's Scale. Qualitatively, materials from 1 to 3 are consid(cid:173)
`ered as soft and from 8 to 10 as hard. Friability (ease of
`fracture) and fibrousness can be of equal importance in mill
`selection. Fibrous materials, eg, plant products, require a
`cutting or chopping action and usually cannot be reduced in
`size effectively by pressure or impact techniques. A mois(cid:173)
`ture content above about 5% will in most instances also
`c:reate a problem and can lead to agglomeration or even
`liquefaction of the milled material. Hydrates will often
`release their water of hydration under the influence of a
`
`high-temperature milling process and thus may require cool(cid:173)
`ing or low-speed processing.
`Methods and Equipment- When a narrow particle-size
`distribution with a minimum of fwes is desired, closed(cid:173)
`circuit milling is advantageous. This technique combines
`the milling equipment with some type of classifier (see Par(cid:173)
`ticle-Size Measurement and Classification). In the sim(cid:173)
`plest arrangement, a screen is used to make the separation,
`and the oversize particles are returned to the mill on a
`continuous basis while the particles of the desired s ize p.ass
`through the screen and out of the· grinding chamber. Over(cid:173)
`milling, with its subsequent. production of fines·, thereby is
`minimized. Equipment also has been designed to combine
`the sieving and milling steps into a single operation (see
`Centrifugal-Impact Mills and Sieves).
`In order to avoid contamination or deterioration, the
`equipment used for pharmaceuticals should be fabricated of
`materials which are chemically and mechanically compati(cid:173)
`ble with the substance being processed. The equipment
`should be disassembled readily for ease in cleaning to pre(cid:173)
`vent cross-contamination. Dust-free operation, durability,
`simplified construction and operation and suitable feed and
`outlet capacities are additional considerations in equipment
`selection.
`While there is no rigid classification of large-scale com(cid:173)
`minution equipment, it generally is divided into three broad
`categories based on feed and product size:
`
`1. Coarse crushers (eg, jaw, gyratory, roll and impact crushers).
`Intermediate grinders (eg, rotary cutters, disk, hammer, roller
`2.
`and chaser mills).
`3. Fine grinding mills (eg, ball, rod, hammer, colloid, and fluid(cid:173)
`energy mills; high-speed mechanical screen and centrifugal classifier).
`
`Machines in the first category are employed ordinarily
`where the size of the feed material is relatively large, ranging
`from 1lj2 to 60"' in diameter. These are used most frequently
`in the mineral crushing industry and will not be consid(cid:173)
`ered further. The machines in the second category are used
`for feed materials of relatively small size and provide prod(cid:173)
`ucts which fall between 20- and 200-mesh. Those in the
`third category produce particles, most of which will pass
`through a 200-mesh sieve, though, often the particle size of
`the products f:rom fine grinding mills is well into the micron
`range.
`The comminution effect of any given operation can be
`described mathematically in terms of a matrix whose ele(cid:173)
`ments represent the probabilities of transformation of the
`various-size particles in the feed material to the particle
`sizes present in the output. The numerical values of the
`elements in the transition matrix can be determined experi(cid:173)
`mentally and the matrix serves to characterize the mill.
`Matrices of this type are frequently a function of feed rate
`and feed partide-size distribution but are useful in predict(cid:173)
`ing mill behavior. Multiplication of the appropriate com(cid:173)
`minution matrix with the feed-size distribution line-matrix
`yields the predicted output-size distribution.
`Intermediate and Fine Grinding Mills-The various
`types of comminuting equipment in this class generally em(cid:173)
`ploy one ofthree basic actions or, more commonly, a combi(cid:173)
`nation of these actions.
`
`1. Attrition-This involves breaking down of the material by a rub(cid:173)
`bing action between two surface$. The procedure is particularly appli(cid:173)
`cable to the grinding of fibrous materials where a tearing action ~
`required to reduce the fibers to powder.
`.
`.
`2. Rolling- This uses a heavy rolling member to crush and pulvenze
`the material. Theoretically, only a rolling-crushing type of action is
`involved, but in actual practice sonte slight attrition takes place between
`the face of the roller and the bed of the milL
`3. Impact- This involves the operation of hammers (or bars) at high
`speeds. These strike the lumps of material and throw them against each
`other or against the walls of the containing chamber. The impact causes
`large particles to split apart, the action continuing until small particles of
`
`' I,
`
`
`
`required size are produced. Lo some instances high-velocity air or cen(cid:173)
`t.rifugal force may be used to generate high-impact velocities.
`
`Roller Mills in their basic form consist of two rollers re(cid:173)
`volving in the same direction at different rates of speed.
`This principle, which provides particle-size reduction main(cid:173)
`ly through compression (crushing) and shear has been ap(cid:173)
`plied to the development of a wide variety of roller mills.
`Some use multiple smooth rollers or corrugated, ribbed or
`saw-toothed rollers to provide a cutting action. Most allow
`adjustment of the gap between roUers to control the particle
`size of the product. The roller mill is quite versatile and can
`be used to crush a variety of materials.
`An example of a pharmaceutical roller mill is the Crack-U(cid:173)
`Lator, in which a series of ribbed rollers are adjusted to
`reduce sequentially the particle size of the product to pro(cid:173)
`duce the desired distribution. The design allows particles
`which are smaller than the gap between the rollers to pass to
`the next stage without unnecessary size reduction, thus re-
`ducing f'rnes.
`}
`Hammer Mills consist of a rotating shaft on which are
`mounted either rigid or swing hammers (beaters}. This unit
`is enclosed with a chamber containing a grid or removable
`screen through which the material must pass. On the upper
`part is the feed hopper. As the material enters the chamber,
`the rapidly rotating hammers strike against it and break it
`into smaller (ragments. These are swept downward against
`t be screen where they undergo additional "hammering" ac(cid:173)
`t ion until they are reduced to a size small enough to pass
`th.rough the openings and out. Oversize particles are hurled
`upward into the chamber where they also undergo further
`blows by the revolving hammers.
`These mills operate at high speed and generally with con(cid:173)
`trolled feed rate. Both impact and attrition provide the
`grinding action. Particle size is regulated by rotor speed,
`feed rate, type and number of hammers. clearance between
`hammers and chamber wall and discharge openings. At a
`constant screen opening, the speed of the mill and the thick(cid:173)
`ness of the screen will affect the particle size of the milled
`powder,3 as shown in Fig 88-1. The higher the speed, the
`steeper the approach angle of the particle to the screen hole.
`Thus, for any screen size opening, the higher the blade
`speed, the smaller the particle obtained.
`Increasing the
`screen thickness will have a similar effect. In general flat(cid:173)
`edged blades are most effective for pulverizing, while sharp·
`edged blades will act to chop or cut fibrous materials.
`The FitzMill Comminutor (Fig 88-2) is an example of this
`type of mill. It can be used in either the hammer or knife(cid:173)
`blade configuration and can be fitted with a wide range of
`screen sizes to fulfill a variety of mming specifications.
`
`(o)
`
`'
`
`~~o-,
`SCREEN SIZE
`
`,o LOW
`, /
`:;;;;;;HIGH
`, 0 THIN
`, /
`/ .
`/ ,o' TliiCK
`~:::~
`
`/
`I
`I /I
`
`(b)
`Fig 88- 1. The influence of (a) mill speed and (b) screen thickness on
`particle size at a constant screen-opening size. 3
`
`POWDERS
`
`1617
`
`Fig 88-2. EZ-Ctean FitzMitl Comminutor (courtesy, Fitzpatrick).
`
`A wide range of particle sizes down to the micron size can
`be produced by these mills. · The particle shape, however, is
`generally sharper and more irregular than that produced by
`compression methods. When very fine particles are desired,
`h11.tt1mer mills can be operated in conjunction with an air
`classifier. Under such conditions a narrower particle-size
`distribution and lower grinding temperatures are obtained.
`Fine pulverizing of plastic material can be accomplished in
`these mills by embrittlement with liquid N 2 or C02 or by
`jacketing the grinding chamber.
`Centrifugal-Impact Mills and Sieves are useful to mini(cid:173)
`mize the production of frne particles, since their design com(cid:173)
`bines sieving and milling into a single operation. T he mill
`consists of a nonrotating bar or stator which is fixed within a
`rotating sieve basket. The particles which are smaller than
`the hole size of the sieve can pass through the mill without
`comminution; however, the particles or agglomerates larger
`than the hole size are directed by centrifugal force to impact
`with the stator. The sieve baskets also can be constructed to
`have a cutting edge which can aid in particle-size reduction
`without impact with the stator. The Quick Sieve (Fig 88-3),
`Turbo Sieve and Co Mill are examples of this type of mill.
`Cutter Mills are useful in reducing the particle size of
`fibrous material and act by a combined cutting and shearing
`action. They consist of a horizontal rotor in which are set a
`series of knives or blades. This rotor turns within a housing
`into which are set stationary bed knives. The feed is from
`the top and a perforated v.late or screen is set into the bottom
`of the housing through which the finished product is dis(cid:173)
`charged. The particle size and shape is determined by the
`plate size, gap between rotor and bed knives and size of the
`openings. A number of rotor styles are available to provide
`different particle shapes and sizes, though cutter mills are
`normally not designed to produce particles frner than 80- to
`100-mesh.
`Attrition Mills make use of two stone or steel grinding
`plates, one or both of which revolve to provide grinding
`mainly through attrition. These mills are most suitable for
`friable or medium-hard, free-flowing material.
`The Sprout-Waldron double runner attrition mill is an
`
`
`
`1618
`
`CHAPTER 88
`
`Fig 88-4. Single jar mill.
`
`Vibrating Ball Mills, which also combine attrition and
`impact, consist of a mill shell containing a charge of balls
`similar to rotating baiJ mills. However, in this case the shell
`is vibrated at 11ome suitable frequency, rather than rotated.
`These mills offer the advantage of being free of rotating
`parts, and thus can be integrated readily into a particle
`classifying system or other ancillary equipment. Further(cid:173)
`more, there have been several studies which have demon(cid:173)
`strated that the vibrating ball mill will grind at rates often as
`high as 20 to 30 times t.hat of the conventional tumbling mill
`and offer a higher order of grinding rate and efficiency than
`other prevailing milling procedures.
`Fluid-Energy Mills are used for pulverizing and classify(cid:173)
`ing extremely small particles of many materials. The mills
`have no moving parts, grinding being achieved by subjecting
`the solid material to streams of high velocity elastic fluids,
`usually air, steam or an inert gas. The material to be pulver(cid:173)
`ized is swept into violent turbulence by the sonic and super(cid:173)
`sonic velocity of the streams. The particles are accelerated
`to relatively high speeds and when they collide with each
`other the impact causes violent fracture of the particles.
`One type of fluid-energy mill is shown in Fig 88-5. The
`elastic grinding fluid is introduced thr ough nozzles in the
`lower port ion of the mill under pressures ranging from 25 to
`300 psi. In this way, a rapidly circulating flow of gas is
`generated in t he hollow, doughnut-shaped mill. A Venturi
`feeder introduces the coarse material into the mill and the
`
`Fig 88-5. The Jet-0-Mizer fluid energy mill (counesy, Fluid Energy).
`
`Fig 88-3. Quick Sieve (courtesy, Glatt Air).
`
`example of a mill which uses two rotating disks revolving in
`opposite directions. The particle-size Teduction is con(cid:173)
`troiJed by varying t he speed at which the disks revolve, the
`space between the disks and the size and number of ridges
`a nd indentations in the face of the disks. By appropriate
`combination with a dassifier, particle sizes ranging from 10-
`mesh to 20 ~m can be ob tained by these attrition mills.
`Chaser Mills arc so called because two heavy granite
`stones, or chasers, mounted vertically like wheels and con(cid:173)
`nected by a short horizontal shaft, are made to revolve or
`chase each other upQn a granite base sunounded by a curb.
`Revolution of the chasers produces an upward current of air;
`t his carries over the tighter particles, which fall outside the
`curb and subsequently are collected as a fine powder.
`Pebble or Ball Mills, sometimes called "pot mills" or "jar
`mills," are operated on the principle of attrition and impact,
`the grinding being effected by placing the substance in jars
`or cylindrical vessels, tined with porcelain or a similar hard
`substance and containing "pebbles" or " balls" of flint, por(cid:173)
`celain, steel or stainless steel. These cylindrical vessels re(cid:173)
`volve horizontally on their long axis and the tumbling of the
`pebbles or balls over one another and against the sides of the
`cylinder produces pulverization with a minimum loss of ma(cid:173)
`terial. Ball-milling is a relatively slow process and generally
`requires many hours to produce material of suitable fine(cid:173)
`ness. In order to keep the grinding time within reasonable
`limits, coarse material (> 10-mesh) should be preground be(cid:173)
`fore introduction into a ball mill. Fig 88-4 shows a sectional
`view of a single jar mill. Rod mills are a modification in
`which rods about 3 in shorter than the length of the mill are
`used in place of balls. This results in a lower production of
`fines and a somewhat more granular product.
`
`
`
`POWDERS
`
`1819
`
`Table t- Definition of Statistical Diameters"
`
`Type of mean
`diameter
`
`Statistical
`definition
`
`Arithmetic
`
`'Xndft,n
`
`Diameter moment
`
`Xnd2/];nd
`
`Surface momellt
`
`'Znd3f'i,nd2
`
`Volume moment
`
`Xnd4ft,nd3
`
`Surface
`Volume
`
`(Ind'!J;n) 112
`('Znd3/In) 113
`
`Desc:rlptlon
`
`Mean diameter
`weighud by number
`Mean diameter
`weighted by particle
`diameur
`Mean diameter
`weighted by particle
`surface
`Mean diameter
`weighud by particle
`volume
`Root mean square
`
`• When grouped data are uoed. n is the number of particles in a size interval
`characterized by a diameter, d.
`
`ter is incapable of totaJJy defining the powder. Measure(cid:173)
`men ts must be made over the total range of sizes present.
`Statistical diameters, for example, are useful measures of
`central size tendency and are computed from some mea(cid:173)
`sured property that is a function of size and related to a
`linear dimension. For irreguJar particles the assigned size
`will depend strongly on the method of measurement.
`Once a method of assignment of numerical value for the
`diameter, surface area or other parameter has been estab(cid:173)
`lished, the average value computed for the parameter is
`dependent on the weighting given the various sizes. Mean
`particle diameter is the most important single statistical
`parlUDeter since, if the proper diameter is chosen, the vari(cid:173)
`ous other parameters of interest such as specific surface
`axea, number, meao particle weight, etc, often may be calcu(cid:173)
`lated. Thus, the choice of the mean diameter to be mea(cid:173)
`sured or calculated is based on its intended use. For exam·
`ple, specific s urface area, which may control drug dissolu·
`tion, frequently can be related to the root-mean square
`diameter. Depending on the method of measurement, vari(cid:173)
`ous diameters are obtained; these will be discussed later.
`The particle djameters most comm only used are listed in
`T able I.
`Size Djstributions-As has been pointed out, size distri(cid:173)
`butions are often complex and no single particle size param(cid:173)
`eter is sufficient to characterize or permit prediction of the
`many bulk properties of pharmaceutical interest, eg, flow
`characteristics, packing densities, compressibility or segre(cid:173)
`gation tendencies. T hus, descriptions beyond the central
`tendency provided by the various mean diameters are need(cid:173)
`ed. These generally take the form of equations or charts
`that describe in detail the distribution of particle size. In
`measuring particle size it is important rrrst to select the
`parameter that is r elated to the ultimate use of the product,
`and then select the method that will measure this parameter.
`Certainly, m ore-useful infor mation would be gained if the
`particle ·size of a powder used in a suspension were deter(cid:173)
`mined by sedimentation than by microscopy1 or if the total
`surface axea of the particles were the critical factor (as in use
`as an adsorbant) by the more useful method of permeability
`or gas adsorption.
`Particles can be classified by determining the number of
`particles in successive size ranges. The distribution can be
`represented by a bar graph or histogram (Fig 88-7), where
`the widths of the bars represent the .size range and the
`heights represent the frequency of occurrence in each range.
`A smooth curve drawn through the midpoints of the tops of
`the bars in this case results in a normal probabilit y size·
`distribution curve. A line drawn through the center of the
`curve to the abscissa divides the area into two equal parts
`and represents the mean value. Since a number of other
`
`Fig 88-6. CentriMII, a centrifugal-impact mill, available In models
`ranging from 2 to 250 hp. A: Spinning rotor; B: rotor hub disks; C:
`Impacters (courtesy, Entoleter).
`
`p.articles enter into the jet stream of rapidly moving gas.
`The raw material is pulverized quickly by mutual impact in
`the reduction chamber. As the fme particles form they are
`carried upward in the track. Particles are ground simulta(cid:173)
`neously and classified in this process. The smalJer particles
`are entrapped by the drag of gas leaving the mill and are
`carried out to a collecting chamber or bag. Centrifugal force
`at the top of the chamber stratifies the larger, heavy parti(cid:173)
`cles and their greater m.omentum carries them downward
`and back to the grinding chamber.
`A major advantage of the fluid-energy mill is t hat the
`cooling effect of the grinding fluid as it expands in the grind (cid:173)
`ing chamber more than compensates for the moderate heat
`generated during the grinding process. Another advantage
`is the rather naxrow range of particle sizes produced. When
`precise control of particle size is an important factor, the
`fluid-energy mill produces very narrow ranges of particles
`with minimum effort.
`One major disadvantage is the necessity of controlling the
`feeding of the coarse, raw material into the jet stream. Of(cid:173)
`ten, the feeding device becomes clogged by a clump of mate(cid:173)
`rial, and special feeding devices must be built to produce a
`uniform rate of feed.
`Centrifugal-Impact Pulverizers also have been found to
`be effective for the reduction of the particle size of a wide
`variety of materials ranging ftom very soft, organic chemi(cid:173)
`cals to hard, abrasive minerals. In addition, this type of mill
`is suited well for the sjze reduction of heat-sensitive sub(cid:173)
`stances. BasicalJy, in these pulverizers, the material is fed
`into the center of a spinning rotor w.hich applies a high
`centrifugal force to the particles. The material, thus accel(cid:173)
`erated, moves toward t he impactor set at the periphery of
`the rotor. On striking these impactors the material is hurled
`against the outer casing where fmal reduction is achieved.
`Processed material is removed from tho bottom of the coni·
`cal discharge hopper (Fig 88-6). Particle-size reduction in
`the range of 10- to 325-mesh can be obtained with this type
`of mill with a minimum of fmes.
`
`Particle-Size Measurement and Classification
`
`Size and Distribution
`Statistical Parameter s-Monodisperse systems of par(cid:173)
`t icles of regular shape, such as perfect cubes or spheres, can
`be described completely by a si:nglc parameter, ie,length of a
`side or diameter. However, when either nonuniform size
`distributions or an isometric shapes exist, any single parame-
`
`
`
`1820
`
`CHAPTER 88
`
`>(cid:173)u z
`
`lJJ
`::::>
`0
`lJJ a:
`u.
`
`SIZE
`Fig 88-7. Symmetrical particle-size distribution curve.
`
`Size
`Fig 88-8. Skewed particle-size distribution curve.
`
`symmetrical distributions could have this same midpoint, a
`term to describe the scatter about the mean value is needed.
`Standard deviation (the root-mean square deviation about
`the mean) serves to define the spread of the curve on either
`side of the midpoint.
`Most particulate material cannot, however, be described
`by a normal distribution curve. . The resultant curv