UNIT-I caer PHARMACEUTICAL ? ENGINEERING Size Reduction BP304T Download “GDC CLASSES” App From Play Store for FREE Pharma Study Material & MCQsSIZE REDUCTION | INTRODUCTION MECHANISM LAWS GOVERNING IN SIZE REDUCTION FACTORS AFFECTING IN SIZE REDUCTION HAMMER MILL BALL MILL FLUID ENERGY MILL EDGE RUNNER MILL END RUNNER MILL he oy v7 ir ha Me ee COMET ESCs)* Size reduction is a process in which the particle size of a solid is made smaller. The term size reduction is applied to ways in which particles of solids are cut or broken into smaller pieces. Size reduction is necessary if the starting material is too coarse, and the final product needs to be a fine powder. » ADVANTAGES ++ CONTENT UNIFORMITY * Mixing of different ingredients can be effective, if the particle size is uniform and small. + Size reduction ensures this objective. * Particles of optimum size are desirable for effective mixing. + UNIFORM FLOW + Smaller particle size and controlled size distribution promote the flow of the powder into dies during compression of tablets. * The same principles are used in the production of capsules. “+ EFFECTIVE EXTRACTION OF DRUGS + Smaller particles allow rapid penetration of menstruum or solvent into the tissue or cells of vegetable and animal origin (liver and pancreas). * Asaresult, extraction or leaching of active constituents becomes effective and complete in preparation of galenicals . The time required for extraction can be shortened. For example, pancreas is subjected to grinding action for the extraction of insulin. Es a 6 Te Ce ke a aC mT STU Struct)+ EFFECTIVE DRYING * Drying of a granular mass can be rapid and effective, if the size of granules is small and uniform. * Such techniques are used in the production of tablets. * Similarly drying of medicinal plan parts can be quick and fast after size reduction. * IMPROVED PHYSICAL STABILITY * In case of suspensions and emulsions, the rate of sedimentation decreases to a large extent ifparticle size is small “ IMPROVED DISSOLUTION RATE + Size reduction increases surface area , which facilitates intimate contact of solid particles and gastric or intestinal juices. * Thus, the rate of dissolution enhances. ++ IMPROVED RATE OF ABSORPTION + The smaller the particle size, the faster is the absorption, because of enhanced dissolution. » DISADVANTAGES «* DRUG DEGRADATION * Drug decomposition is possible due to the heat produced during milling Thermo-labile substances are the most affected. The increased surface area also facilitates drug decomposition owing to enhanced dissolution Cooling support systems are provided to decrease the heat in milling equipment. Drugs containing waxy materials become soft due to heat generated during milling Therefore the feed is chilled before milling. Sa) Toro) 8 (eae Pe WRC Ue ss Lemme)** POOR MIXING Normally, very small particles possess strong cohesive forces, hence, aggregation of particles is possible. Aggregation inhibits the effective blending of different additives. An increase in surface area may promote the adsorption of air, which may inhibit wettability of the drug during production. Therefore, optimum particle size is desirable to improve blending and to avoid poor mixing CONTAMINATION * During milling and grinding, the grinding surfaces wear off, the particles of which are present as impurities in the powder. * Such type of mills should be avoided, when drugs of high purity are required. A particle’s size can be decreased by reducing its surface area, resulting in smaller particles and increasing solutions rates. Increasing the rate of extraction; size reduction directly affect the rate of extraction. Particle with smaller sizes penetrate menstruum more readily , speeding up the extraction process. For many pharmaceutical dosage forms, effective mixing requires smaller particles sizes. Increasing rate of absorption is associated with decreasing particle size. Therefore , reducing the size a medication helps to increase bioavailability, such in the case of griseofulvin. By, reducing particle size , you can increase drying speed and increase effective surface area. Filtration is possible when particles are separated according to their sizes. “) Download “GDC CLASSES” APP > Goose Py pHARMA EXAM PREPARATION SIMPLIFIEDMECHANISM The mechanism of size reduction depends upon the nature of the material, and each material requires different treatment. Fracture generally occurs along the Compression lines of weakness. During size reduction, fresh surfaces are created or existing cracks and fissures are opened up, wherein the tf former requires more energy. Cutting There may be a tendency that after processing, agglomerates of particles are formed. Size reduction is an energy-inefficient process because a small amount of energy is required to subdivide the particles. A lot of the energy is spent overcoming the friction and inertia of machine parts and the friction between particles and deforming the particles without breaking them. This energy is released as heat. MODE OF STRESS APPLIED IN SIZE REDUCTION IMPACT * When a substance is more or less immobile and is struck by a fast- moving object, or when a moving particle collides with a stationary surface, impact occurs. The material is crushed in both cases into smaller pieces. Download “GDC CLASSES” APP > Goose Py pHARMA EXAM PREPARATION SIMPLIFIED* Because the substance is hit by a moving hammer and the particles created are subsequently hurled against the machine’s shell, both of these things usually happen. + Impact forces are general-purpose forces that can be found in the coarse, medium and fine grinding of a wide range of materials. ** COMPRESSION *In this mechanism, the material is crushed by the application of pressure. * Compressive forces are used for the coarse crushing of hard materials. * Coarse crushing implies reduction to a size of about 3 mm. ++ ATTRITION ° Attrition applies pressure to the material in the same way compression does, but the surfaces move relative to each other, resulting in shear forces that break the particles. When the size of the products can reach the micrometre range, shear or attrition forces are used in fine pulverization. Ultra-fine grinding is a phrase that is sometimes used to describe procedures that produce particles in the sub-micron range. * Cutting lowers the size of solid materials by separating them into smaller particles via mechanical action (sharp blade/s). Cutting is a technique for breaking down big chunks of material into smaller bits with a defined shape that can be processed further, such as powders and granules. Attrition | ©) Download “GDC CLASSES” APP > GoocePly pHARMA EXAM PREPARATION SIMPLIFIED> RITTINGER'S THEORY * According to the Rittinger's hypothesis, energy, E required for size reduction of unit mass is directly proportional to the new surface are produced. + Itis expressed as: E=Kg (S,-S,) * Where S,= initial specific surface area, pm? / pm? S,,= new specific surface area, pm? / pm? Kg = Rittinger's constant, energy per unit area, KW.h/pm? E=amount of energy (work done), kW.h >» BOND'S THEORY + According to the Bond's theory, the energy used in crack propagation is proportional to the new crack length produced. * It states that the energy used for deforming or fracturing a set of particles of equivalent shape is proportional to the change in particles dimensions. * According to Bond's theory, the equation can be written as. 1 1 bag Where Kg = Bond's work index, energy per unit mass , kW.h. pm E=2K, initial diameter of particles, pm d,, = new diameter of particles, pm > KICK'S THEORY + According to the Kick's theory, the energy used in deforming or fracturing a set of particles of equivalent shape is proportional to the ratio of the size changes. * It may be expressed as: E=Kxin where K = Kick's constant, energy per unit mass, /KW.h d;= diameter of the particle in the initial stage, pm d, =diameter of the new particle, Sam mc ae a Google Play PHARMA EXAM PREPARATION SIMPLIFIEDQO) FACTORS AFFECTING IN SIZE REDUCTION | * HARD MATERIALS are hard and abrasive. + In general, hard materials are ess of such materials can lead to abrasive r of s, which then cause contamination. *~ FIBROUS MATERIALS r etc, are e and cannot be crushed by pressure or impact. + Fibrous materials are t * They mustbet x mi are processed in two stages to get fine powders. * FRIABLE MATERIALS are re along well-defined planes. s can be easily converted to smaller particles. * Such materials are milled by the mechanisms such as a * For example, and flui«+ ELASTIC MATERIALS * Synthetic gums, waxes and resins become soft and plastic during milling. * These low-melting substances should be mill chilled before milling. * Such materials are milled using hammer mill. mill, colloid mill or fluid energy HYGROSCOPIC MATERIALS + Substances such as potassium carbonate absorb moisture rapidly. * This wet mass sticks and clogs the mill. * They are prepared in a closed system such E s ey as porcelain ball mill. SOLVATED MATERIALS + Sodium sulphate and other hydrates liberate water during milling and cause clogging of the mill MELTING POINT * Solids with low melting points often become soft and melt owing to the heat generated during milling. fl * Such materials are chilled before milling, THERMOLABILITY * Certain substances undergo degradation reactions such as hydrolysis and oxidation due to the presence of moisture and atmospheric oxygen. They should be milled in a closed system with an inert atmosphere of carbon dioxide or nitrogen. Vitamins and antibiotics are milled using fluid energy and ball mills. = a 6 ; ha Me ee COMET ESCs)“* MOISTURE CONTENT * Presence of more than 5% water hinders the milling process and produces a sticky mass. ° The effect is more pronounced, when the concentration of water is more. * Ingeneral, materials with moisture content below 5% are suitable for dry grinding and from 5% to 50% are suitable for wet grinding. QO HAMMER MILL » INTRODUCTION * Hammer milling is a high energy process of reducing particle size (comminution) by impact with rapidly moving hammers. Water Pipe Raw Ore Feed Hopper Crushing Chamber * The hammer mill operates on the principle of impact between rapidly moving hammers mounted on a rotor and the powder material. Sam cae Google Play PHARMA EXAM PREPARATION SIMPLIFIED» CONSTRUCTION The hammer mill consists essentially of a high speed rotor turning inside a cylindrical casing. The rotor is mounted ona shaft which is usually horizontal. The swing hammers are pinned to a rotor disk. The hammers are rectangular bars of metal with plain or enlarged ends. In this mill, the particles are broken by the sets of swing hammers. The product falls through a grate or screen which forms the lower portion of the casing. Several rotor disks each carrying four to eight swing hammers are often mounted on a single shaft. The rotor disk diameter ranges from 150 mm to 250 mm. As the hammers are hinged, the presence of any hard material does not cause damage tothe equipment. The hammers can be readily replaced when they worn out. » WORKING The hammers are allowed to be in continuous motion(8000 to 15000 revolutions per minute). The feed material is placed into the hopper, which flows vertically down and then horizontally, while hammers are in continuous motion. These rotating hammers beat the material to yield smaller particles. Then, these particles pass through the screen. Due to the tangential exit, the size of the particles is considerably smaller than the aperture of the screen. The hammers act as a centrifugal fan, so that large amount of air is drawn through the mill. In most cases, this is sufficient to counteract the heat generated during milling. Download “GDC CLASSES” APP Google Play PHARMA EXAM PREPARATION SIMPLIFIEDThe fineness of the product can be regulated by altering v Rotor speed v Feed rate v Clearance between hammers and grinding plates, ¥ Number and type of hammers, v Size of the discharge opening ay fi Fi Nag ie High speed AE s x 5S Low speed 7 Thin screen, 46-” Thick screen Mesh size of o S| the sieve ee & f the speed ) Influence of the thickness of ) apeaten ae g the screen on particle size ADVANTAGES Hammer mill is easy to setup (install), dismantle and clean up. Scale-up problems are minimum provided same type of mill is used. Various types of feed stock can be handled using screen of different sizes. Hammer mill occupies small space It is versatile, i.e. speed and screen can be changed rapidly As it is operated in a closed environment, dust can be reduced and explosion hazards can be prevented. > DISADVANTAGES The screens may get clogged. Heat buildup during milling is more, therefore, product degradation is possible. Wearing of mill and screen is more with abrasive materials. Hammer mills cannot be employed to mill sticky, fibrous and hard materials. 3) Download “GDC CLASSES” APP > Goose Py pHARMA EXAM PREPARATION SIMPLIFIED» USES ** FOOD PRODUCT GRINDING * Food processing industries use hammer mills to grind various types of legumes, mainly soya, nutshells, groundnuts, and different types of beans. «+ POWDER PRODUCTION * Various types of hammer mills are used for powder making in the chemical and pharmaceutical industries. The required ingredients are crushed in hammer mills to obtain an intermediate grade of powder. «+ MATERIAL SIZE REDUCTION * Hammer mills are used for micronization in pharmaceutical industries. The medical grains need to fit inside the capsule packaging in precise quantities. Thus, they are micronized by hammer mills before they are packaged. * MIXING OF SOLID DRY & FIBROUS MATERIAL * They are used for combining two solid powders to produce a consistent mixture of two fibrous solid ingredients. « IMPROVE ACTIVENESS OF AN INGREDIENT + Many ingredients can bring out active reactions when added to certain formulations. * These ingredients are crushed slightly to improve their activeness. Sl Te ac =o acne Pe WRC Ue ss Lemme)Q BALL MILL > INTRODUCTION Feed in Out of balance weight * A pulverizing machine consisting JL Ming bats \ of a rotating drum which contains pebbles or metal balls as the grinding implements. * These are also known as tumbling ; Flexible couping Spring mounting mill. to drive motor * The ball mill works on the principle of impact between the rapidly moving balls and the powder material, both enclosed in a hollow cylinder. * At low speeds, the balls roll over each other and attrition (rub bing action) will be the predominant mode of action. * Thus, in the ball mill, impact or attrition or both are responsible for the size reduction. » CONSTRUCTION * Ball mill consists of a hollow cylinder, which is mounted on a metallic frame in such a way that it can be rotated on its longitudinal axis. The cylinder is made of a metal and is usually lined with chrome. The cylinder contains balls that occupy 30 to 50 % of the mill volume. The weight of the balls is kept constant. The ball size depends on the size of the feed and the diameter of the mill. Balls are made of steel, iron or stoneware. These act as the grinding medium. » WORKING The drug to be ground is put into the cylinder of the mill in sucha quantity that it is filled to about 60% of the volume. A fixed number of balls are introduced and the cylinder is closed. The mill is allowed to rotate on its longitudinal axis. Es a > ; eye Tal y(t [oor rats e Cus sl}“> LOW SPEEDS * The balls roll over each other and attrition will be a predominant mode of stress. This mode of attrition is used for wet grinding. It may be useful to add surface active agents to prevent agglomeration. “+ CORRECT SPEED * The centrifugal force just occurs, as a result the balls are picked up by the mill wall and carried nearly to the top, where they break contact with the wall and fall to the bottom. In this manner, impact stress is also induced and the size reduction is made effective. ++ HIGHER SPEEDS * The balls are thrown out to the wall by centrifugal force. Hence, grinding will not occur. The compression by the balls against the wall is not sufficient for effective comminution of the substance. » ADVANTAGES It can produce very fine powder. It is used for batch operation. It can be made continuous operation by including a chamber next to the cylinder. These are separated using a sieve. Sam cae Google Play PHARMA EXAM PREPARATION SIMPLIFIED* Ball mill is suitable for both wet and dry grinding processes. * Toxic substances can be ground, as the cylinder is a closed system. * Since the mill is a closed system, sterility can be achieved. » DISADVANTAGES The ball mill isa very noisy machine. Wear occurs from the balls as well as from the casing, which may result in contamination of the product. Ball milling is a slow process. The rate at which energy can be applied is limited, because it depends on the acceleration of the balls, which is influenced by the gravitational force. Soft, tacky, fibrous material cannot be milled by ball mill. » USES * The ball mill is used for grinding materials such as coal , pigments , and feldspar for pottery. Stainless steel balls are preferred in the production of ophthalmic and parenteral products , as there is a less chance of contamination due to wear. Ball mill at low speeds is used for milling dyes , pigments and insecticides. QO FLUID ENERGY MILL > INTRODUCTION + A pulverizer, micronizer, and jet mill is also known as a fluid energy mill. It’s utilized for fine grinding and controlling particle size. The particles are reduced using an attrition and impact mechanism involving air or inert gas injected through the nozzles in the chamber. This mill is primarily used to finely grind heat-sensitive materials. he ry v7 ir eye Tal y(t MEU ste C) Ure onal)Centrifuging action throws coarser particles outwards ~Classitier removes. fine particles. and fluid Solids intet “ Zone of = turbulence ~ Fluid inlet jets > PRINCIPLE + Fluid energy mill operates on the principle of impact and attrition. * In this equipment, the feedstock is suspended within a high velocity air stream. * Milling takes place because of high velocity collisions between the suspended particles. >» CONSTRUCTION * Fluid energy mill consists ofan elliptical pipe. ° The mill surface may be made of either soft stainless or tough ceramics. * Grinding nozzles may be placed tangential or opposed to the initial flow path of a powder. * Inert gases can be used to minimize or eliminate the oxidation of susceptible compounds. * Venturi feeder is provided in the path of the airflow. * An outlet with a classifier is fitted to allow the escape of air. Download “GDC CLASSES” APP Google Play PHARMA EXAM PREPARATION SIMPLIFIED> WORKING A nozzle at the bottom of the loop injects air at very high pressure. Compressed air with a pressure between 600 kilopascals and 1.0 megapascals is commonly used. Due to the high velocity of the air, turbulence is produced. By feeding the solids into the stream, turbulence is created. Turbulence causes particles to collide and attrit between each other. By incorporating a classifier into the process, the system collects only fine particles for processing as products, while larger particles are sent back into the air stream for further reduction in size. To feed the mill, raw materials have been reduced in size and screened to 100 meshes A;smm or smaller product is produced. > ADVANTAGES It hasno moving parts, hence, heat is not produced during mill It is rapid and an efficient method for reducing powders to 30mm or less. Since there is no wear of the mill , contamination is not possible. > DISADVANTAGES * Fluid energy mill is not suitable for milling of soft , tacky and fibrous materials. * The equipment is expensive. » USES * Used to reduce the particle size of most of the drugs such as antibiotics and vitamins. * When strict quality control is desirable for the purpose of better absorption , this millis the preferred one. Sam cae Google Play PHARMA EXAM PREPARATION SIMPLIFIEDQO) EDGE RUNNER MILL » INTRODUCTION Crank shaft * A machine consisting of one or more — oles heavy steel rolls or grindstones set on a horizontal shaft rotating round _ *)- a pan or trough that is used for crushing stone, fibrous matter for ®¢ ee papermaking, or other material. >» PRINCIPLE The size reduction is done by crushing (compression) due to heavy weight of stones. Shearing force is also involved during the movement of the stones. » CONSTRUCTION It consists of two heavy rollers and may weigh several tons. The rollers move on a bed, which is made of stone or granite. Eachroller has a central shaft and revolve on its axis. Further, the rollers are mounted on a horizontal shaft and move around the bed. » WORKING ° The material to be ground is placed on the bed. With the help of a scrapper, it is kept in the path of the stone wheel. The stones revolve on their axes, and at the same time travel around the shallow stone bed. The outer part of the wheel has to travel a greater distance so that size reduction is achieved by shearing as well as the inner, as crushing. The material is ground for a definite period. The powder is collected and passed through a sieve to get powder of the required size. It isa batch process. prea con me EST UT eae et ats)> ADVANTAGES It produces fine particles * Edge runner mill does not required attention during operation » DISADVANTAGES * Edge runner mill occupies more space than other commonly used mills. * Contamination of the product with roller material is possible. * The milling process is time consuming. * It isnot used for sticky material. » Energy consumption is quite high. > USES * Edge runner mill is used for grinding tough materials to fine powder. * It is still used for plant based products , while more sophisticated mills are used for chemicals and drugs. QO) END RUNNER MILL » INTRODUCTION * An automated version of mortar and pestle size reduction equipment, the end-runner mill is comparable to the edge runner mill. * The friction of material between the mortar and the pestle causes a heavy-weight pestle to revolve when the mortar is rotated by a motor at the base. Pastie — Ub... Material Flanged pate —_ Beveled-cog fitting “) Download “GDC CLASSES” APP > Goose Py pHARMA EXAM PREPARATION SIMPLIFIED> PRINCIPLE * Size reduction is done by crushing due to heavy weight of steel pestle. * Shearing stress is also involved during the movement of mortar and pestle. >» CONSTRUCTION + End-runner mills are mechanical versions of the mortar and pestle method of comminution. This grinding apparatus consists of a stone or metal pestle connected by a shaft. In a shallow steel or porcelain mortar, the pastel revolves on its axis. The pestle is generally in the shape of a dumbbell. At the bottom, the mortar is secured by a flanged plate. Scrappers are located in the center and on either side of the circular pan. The pestle is horizontally positioned and rotates against a powder > WORKING The material to be milled is fed into the centre of the circular mechanical mortar (pan) and is worked outwards by the action of the wheels and mill is operated. The pestle rotates against a bed of powders. Mortar revolves at high speed and causes the pestle to revolve. Scrapers are employed in scraping the material constantly from the bottom of the wheel and are feed back to the wheel were it gets crushed further. Finally, pestle is raised from the mortar manually or automatically to facilitate emptying and cleaning. Sam cae Google Play PHARMA EXAM PREPARATION SIMPLIFIED>» ADVANTAGES It has simple design and thus cleaning and maintenance is easy. It utilizes less electrical power. It produces fine and sometimes very fine particles. Requires less attention during the milling operation. It has no problem of chocking or clogging asit has no sieves for size separation. DISADVANTAGES It runs only on batch operation. It is not suitable for milling sticky materials. Unsuitable for drugs which are hard and unbroken or in slightly broken condition. Machine noise causes lot of noise pollution. It requires scrapper adjustment intermittently. USES It isused to reduce fibrous crude drugs to a fine size. It used for grinding semisolid preparations such as ointments and pastes to fine size. It is used for uniform distribution of the contents in viscous dispersion medium. It can be used for both wet and dry grinding of crude drugs. Sam cae Google Play PHARMA EXAM PREPARATION SIMPLIFIEDQUESTIONS FROM THE ABOVE TOPIC Awa oueUC mere eR ELC CRRA Beast ENCE UC Letom Mel treeTi eToys Payee elias eed oe ee RNB eee see BTA m bE YA reduction? Describe the kick theory? Write objective of size reduction? Short Answer Questions (4 marks) Asiana nm etc ece tae ng Describe the law governing of size reduction? Write short note on factors affecting size reduction? eee lace eerie cd Draw Teme niaa aC Reach TeeC Tele Tee Tite disadvantages of fluid energy mill? ee ere MCR ome ecpac ates exe itl Creed Explain the principle , construction working and diagram of ball mill? Explain the principle , construction working and diagram of erp athibitsas iit leg Explain the principle , construction working and diagram of CU Baetom tlle Explain the principle , construction working and diagram of hammer mill Time to Stu y : eros (Tine Study Smarty & Download “GDC CLASSES” APP > Goose Py pHARMA EXAM PREPARATION SIMPLIFIEDCE eare at rupees(©)=J=J=] (each) Cee ee ber ed 1 STUDY MATERIAL Hard Copy Books @ Hard Copy Books ORT CCRT aD TR SCT @ Live Classes ea TTS Type Penn Also You Can Join recur ae ee) E> Gattis) 1 TO 8™ SEMESTER poreenco coalesce IN PLAY STORE TO plo Rey Nets ld ek AM MUU) ste weet