size reduction sem III.pptx

3rd sem unit 1 size reduction in details
B pharma
Easy to learn
Notes

1. SIZE REDUCTION Dr. (Mrs.) SUPARNA S BAKHLE Associate Prof. PHARMACEUTICS DEPARTMENT PJLCP, NAGPUR 1

2. Size Reduction Size reduction is the process of reducing or breaking of larger particles into small particles. Size reduction is otherwise called as comminution or grinding or pulverization . 2

3. OBJECTIVES OF SIZE REDUCTION Size reduction offers several advantages. Thus it is carried out with some of the following objectives: Improvement in dissolution and absorption of drugs: Size reduction leads to increase of surface area. Thus the rate of dissolution of solid drug particles increases many times after size reduction. Griseofulvin, an antifungal drug, when administered in its micronized form shows better absorption. Likewise, the absorptive power of charcoal and kaolin increases after size reduction due to increase in surface area. Effective extraction of drugs: The extraction from animal glands such as liver and pancreas and from crude vegetable drugs is facilitated with an increase in surface area because solvent can easily penetrate into the tissues resulting in quick extraction of their active constituents. Increased therapeutic effectiveness of drugs: Size reduction results in increase in the therapeutic effectiveness of certain drugs due to enhanced absorption. For example, in the case of griseofulvin, the dose of the drug is reduced to half than that of originally required. Effective mixing of materials: Size reduction produces particles in narrow size range. Mixing of powders with narrow size range is easier. Improved physical appearance: The physical appearance of ointments, pastes and creams can be improved by reducing its particle size. All the ophthalmic preparations and preparations meant for external application to the skin must be free from gritty particles to avoid irritation of the area to which they are applied Improved physical stability: Pharmaceutical suspensions require finer particle size. It reduces rate of sedimentation. 3

4. DISADVANTAGES OF SIZE REDUCTION Drug degradation: During the process of size reduction heat is evolved which leads to decomposition of the substances particularly the thermo-labile ones. Drugs containing waxy materials become soft on account of heat generated during milling. There is a provision for cooling of the mills to lower the temperature during milling. Poor Mixing: Normally, very small particles possess strong cohesive forces, hence aggregation of particles is possible. Aggregation inhibits the effective blending of different additives. Thus size reduction to fine particle size leads to poor mixing. Contamination: During milling and grinding, the grinding surfaces wears off like from ceramic or iron equipment which in turn will lead to contamination of the product. 4

5. Mechanism of Size Reduction Cutting: As the name implies, the material is cut by means of a sharp blade or blades. It is useful for grinding of fibrous or waxy solids. Example is cutter mill Compression: In this method, the material is crushed by application of pressure. Example is roller mill. Impact : Impact occurs when the material is more or less stationary and is hit by an object moving at high speed or when the moving particle strikes a stationary surface. In either case, the material shatters to smaller pieces. Usually both will take place, since the substance is hit by a moving hammer and the particles formed are then thrown against the casing of the machine. Example is hammer mill. Attrition: In attrition, the material is subjected to pressure as in compression, but the surfaces are moving relative to each other, resulting in shear forces which break the particles. It is generally used for fine grinding. Example is fluid energy mill. 5

6. MECHANISMS OF SIZE REDUCTION 6

7. THEORY AND LAWS GOVERNING SIZE REDUCTION When stress is applied on a material it is strained. On removal of the stress it returns to its original condition. Every material has a limit of elasticity which allows the material to be deformed reversibly up till a certain limit. The limit to which the material behaves as an elastic material on being stressed is called as the yield point. Beyond this yield point the material undergoes irreversible deformation. 7

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9. Griffith theory 9  

10. Rittinger’s theory 10  

11. Bond’s theory 11  

12. Kick’s theory 12  

13. Size Reduction Equipments: There are numerous size reduction equipments which can be classified as follows: A : Crushers: ex: edge runner mill, end runner mill. B: Grinders : 1. Impact mill: ex: hammer mill 2. Rolling compression: ex: roller mill 3. Attrition mill: ex: attrition mill 4. Tumbling mill: ex: ball mill C: Ultrafine grinder: ex: fluid energy mill D: Cutting machine : ex: cutter mill 13

14. GENERAL PARTS OF SIZE REDUCTION EQUIPMENT 14

15. Hopper: It is a structure for feeding the material to the mill. Milling Chamber: The milling chamber is the one in which actual size reduction takes place by a particular mode. The chamber consists of rotor and stator Receiver: it can also be called as a discharge chute in which the milled product is collected. Other accessories Sieves or screens are enclosed in the milling chamber to classify the particles by size. Cyclone separator or centrifugal equipment is fitted to the mills for separation of particles by their sizes. Dust collectors are employed in order to collect the fine powder and dust that arise during milling process. Special features: Cooling devices are fitted to the chamber to reduce the heat produced during milling. A closed environment is desirable for milling hygroscopic substances. For this purpose, dehumidified air is necessary. Closed system with inert atmosphere (nitrogen or carbon dioxide) is desirable for milling of drugs such as oxidisable or combustible.   15

16. Hammer Mill 16

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18. Hammer Mill The hammer mill operates in the principle of impact between rapidly moving hammers mounted on a rotor and the powder material. The hammer mill can be either vertical or horizontal type. Hammers are usually made of hardened steel, stainless steel with impact surface made of an extremely abrasive resistant material such as haystellite and carbaloy . Stainless steel hammers are sufficient for pharmaceutical purpose. Hammers may take several shapes. Bar shaped hammers are used extensively. The hammer blades can be with flat edges or sharp edges or both. Hammers may be rigid or swinging type. Free swinging hammers has an advantage that there will be increasing clearance between hammers and screen, if excessive build occurs in the mill. 18

19. The fineness of the product can be regulated by altering: Rotor speed Feed rate Clearance between hammers and grinding plates Number and types of hammers Size of the screen 19

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21. Advantages of Hammer Mill It is rapid in action, and is capable of grinding many different types of materials. They are easy to install and operate, the operation is continuous. There is little contamination of the product with metal abraded from the mill as no surface move against each other. The particle size of the material to be reduced can be easily controlled by changing the speed of the rotor, hammer type, shape and size of the screen 21

22. Disadvantages of Hammer Mill Heat buildup during milling is more, therefore, product degradation is possible. Hammer mills cannot be employed to mill sticky, fibrous and hard materials. The screens may get clogged. Wearing of mill and screen is more with abrasive materials. 22

23. BALL MILL Principle: The ball mill works on the combined process of impact and attrition to bring about size reduction. Impact is produced between rapidly moving balls and the powder material, both enclosed in hollow cylinder. The balls also roll over each other and attrition (rubbing action) between the balls and the particles is also responsible for the size reduction. 23

24. BALL MILL Construction: The 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 length of the cylinder is slightly greater than its diameter. Some models are very large, with cylinders 3 m in diameter, but about 1 m is more common in pharmaceutical practice. The cylinder is made of metal, porcelain or of rubber to reduce abrasion. The cylinder contains balls that occupy 30-50 % of the mill volume which act as the grinding medium.. 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 metal, porcelain or occasionally pebbles are used, when the mill may be described as pebble mill. 24

25. BALL MILL 25

26. BALL MILL Working: The drug to be ground is put into the cylinder of the mill in such a quantity that it is filled to about 60% of the volume (material to void ratio). A fixed number of balls are introduced and the cylinder is closed. The mill is allowed to rotate on its longitudinal axis. The factor of greatest importance in the operation of the ball mill is the speed of rotation described in the figure At low speeds, the mass of balls will slide or roll over each and only a negligible amount of size reduction will occur by attrition. At 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 will not be sufficient for effective comminution of the substance. At correct speed, the centrifugal force just occurs, as a result the balls are picked up by the mill and carried nearly to the top, where they break contact with the wall and fall to the bottom to be picked up. By this means, the maximum size reduction is effected by impact of the particles between the balls and by attrition between the balls. 26

27. Influence of speed on ball mill efficiency 27

28. BALL MILL Uses: Ball mill at low speed is used for milling dyes, pigments & insecticides. Stainless steel balls are preferred in the production of ophthalmic & parental products. Ball mill is used for the final grinding of drugs or for grinding suspensions. Merits: In ball mill, installation, operation and labour costs are low. It is capable of grinding wide variety of materials of different nature and different degree of hardness. It can produce very fine powder. It is used for batch operation. It can also be made continuous by including a classifier in combination with the mill. This will allow the product to be obtained of the desired particle size and oversize material can be returned back for size reduction. Ball mill is equally suitable for both wet and dry grinding processes. It can be used in a completely enclosed form making it suitable for grinding of toxic substances. Since the mill is a closed system, sterility can be achieved. Milling operation can be accomplished in a inert atmosphere, if oxygen sensitive substances are to be milled. Rod or bars can also be used as grinding media. (example: Sticky material are size reduced)   28

29. BALL MILL Demerits : The ball mill is a very noisy machine particularly if the casing is of metal. Wear occurs from the balls as well as from the casing, which may result in contamination of the product. Milling in the ball mill 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.   29

30. Fluid Energy Mill 30

31. Fluid Energy Mill 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. 31

32. FEM (CONSTRUCTION) Fluid energy mill consists of a loop of a pipe, which has a diameter of 20 to 200 mm, depending on the overall height of the loop which may be up to about 2 meters. A fluid, usually air, is injected at high pressure through nozzles at the bottom of the loop, giving rise to a high velocity circulation in a very turbulent condition, Solids are introduced into the stream and, as a result of the high degree of turbulence, impact and attritional forces occur between the particles. A classifier is incorporated in the system, so that particles are retained until sufficiently fine. The feed to the mill needs to be pre-treated to reduce the particles size to the order of 100 mesh, enabling the process to yield a product as small as 5 micrometers or less. Despite this, mills are available which are capable of outputs up to 4 mg per hour. 32

33. FEM Powder is introduced through the inlet of venturi. The air entering through the grinding nozzles transport the powder in the elliptical or circular track of the mill. In the turbulent stream of air, the suspended particles colloid with each other and break. Thus, impact and attrition forces operate in size reduction. The resultant small particles are carried to outlet and removed by cyclone or filters. The coarser particles undergo re-circulation in the chamber on account of its weight. These re-circulated particles colloid again with new in-coming feed stock particles. The powder remains in the mill, until its size is reduced sufficiently. Later it leaves via the sieve. Hence, FEM produces particles with narrow size distribution. 33

34. Advantages and Disadvantages of FEM Uses: Fluid energy mill: Fluid energy mill is used for ultra-fine grinding. Examples are antibiotics, sulphonamides and vitamins. Merits : The particle size of the product is smaller than that produced by any other method of size reduction. Upto 6000 kg of feed is milled per hour. Having a classifier as an integral part of the system permits close control of particle size and of particle size distribution. Feed particles of size 12 mm are easily size reduced. Since there is no wear of the mill, contamination is not possible. Thermolabile substances can be ground since heat is not generated during the milling process. Demerits : Fluid energy mill is not suitable for milling of soft, tacky and fibrous material. The equipment is expensive, because it needs additional accessories particularly fluid energy source and dust collection equipment. 34

35. EDGE RUNNER MILL 35

36. EDGE RUNNER MILL Principle: The edge runner mill consists of two heavy and large rollers made of stone which crush the material by compression. Construction: It consists of two rollers which roll over a bed containing the feed material. The rollers are made of stone or granite and are heavy weighing several tons. The rollers revolve on their axes and at the same time also move around the bed. It is a batch unit. 36

37. EDGE RUNNER MILL Working: The material to be ground is placed over the bed. A scrapper helps the material to be placed in path of the rollers. As the rollers revolve they crush the material by compression. At the same time since they move all along the bed effective size reduction takes place. After grinding the finished product is passed through a sieve to get powder of the desired size. Uses: Edge runner mill is used for grinding tough materials to fine powder. It is still commonly used for plant-based products, while more sophisticated mills are used for chemicals and drugs. Merits: It is easy to operate and monitor the size reduction process in this mill Demerits : The mill occupies more space than other commonly used mills The grinding process is time consuming It is not suitable for sticky materials Energy consumption is quite high Contamination of the material with the roller material is possible due to wear and tear of the machine. 37

38. END RUNNER MILL Principle: An end runner mill consists of a pestle which revolves mechanically in a mortar and crushes the material by compression. Construction: It can be called as mechanical mortar and pestle. It consists of a mortar made of steel which rotates at a high speed. The mortar is fixed to a flanged plate. A pestle is allowed to move in the mortar mechanically. The pestle is dum-bell shaped and crushes the material on account of its weight by compression. A scrapper is attached to the mortar to place the material in contact with the pestle for grinding. The pestle can be raised from the mortar to facilitate emptying and cleaning. 38

39. END RUNNER MILL 39

40. END RUNNER MILL Working: The material to be ground is placed in the mortar. The scraper puts the material in the path of the pestle. The mortar revolves at a high speed. The pestle is placed in the mortar. The rotating mortar causes the pestle to revolve. During this process, size reduction is effected by shearing and crushing. The powder is collected and passed through a sieve to get powder of the desired size. Uses: End runner mill is suitable for fine grinding Merits: The mill is suitable for dry as well as wet grinding Demerits : The mill is not suitable for drugs which are in unbroken or slightly broken conditions. 40

41. Factors affecting size reduction There are many factors which influences the process of size reduction and ultimately the selection of the milling equipments. These can be categorized as follows: Factors related to the nature of raw materials Factors related to the nature of finished product Factors related to safety and economy 41

42. Factors influencing size reduction Factors related to the nature of raw materials Hardness: In general, the harder the material the more difficult it is to reduce in size. Toughness: Toughness is encountered in many pharmaceutical materials such as fibrous drugs, and is often related to moisture content. One can compare the toughness of a green twig with the brittleness of dry one. Toughness will pose a problem as far as size reduction is concerned. Abrasiveness: In general, abrasiveness is a property of hard materials, particularly those of mineral origin and may limit the type of machinery that can be used. Grinding of abrasive materials leads to contamination of the finished product. Stickiness: It is a property that may cause a considerable difficulty in size reduction, for materials may adhere to the grinding surfaces, or the meshes of screens may become choked. Substances that are gummy or resinous may be troublesome, particularly if the method used for size reduction generate heat. Complete dryness may help, and the addition of inert substances may sometimes be of assistance. E.g addition of kaolin to sulphur. Softening temperature: Many of the size reduction processes results in generation of heat, which may cause some substances to soften, and the temperature at which this occurs can be important. Waxy substances, such as stearic acid or drugs containing oils or fats are e.gs that may be affected. With some methods it may be possible to cool the mill, either by a water jacket or passing a stream of air through the equipment. Material structure: Some substances are homogenous in character, but the majority show some special structure; for e.g, mineral substances may have lines of weakness along which the material splits to form flake-like particles, while vegetable drugs have a cellular structure often leading to long fibrous particles. Moisture content: Usually, less than 5 % of moisture is suitable if the substance is to be ground dry; or more than 50 % if it is being subjected to wet grinding. Physiological effect: Some substances are very potent (e.g podophyllum resin or hormone drug) and small amount of dust may have effect on operators. In such cases, enclosed mills may be used to avoid dust; special air extraction systems are desirable and wet grinding also, if possible, as it eliminates the problems entirely. Purity required: Certain types of size reduction apparatus cause the grinding surfaces to wear, and such methods must be avoided if a high degree of purity of product is needed. Similarly, some machines will be unsuitable if cleaning between batches of different materials is difficult. Ratio of feed size to product size: Generally speaking, machines that produce a fine product require a fairly small feed size. Thus, it may be necessary to carry out the size reduction process in several stages with different equipment; for e.g, preliminary crushing, followed by coarse grinding and then fine grinding. 42

43. Factors related to the nature of finished product The nature of the finished product also influences the selection of the equipment. Particle size: If extreme particle size reduction is required, it may be essential to recycle larger particles. This can be achieved by screening the discharge material and returning the over-size particle for further milling. Moderately coarse or coarse powders are easily obtained with the help of impact mills operating on high speeds. Ease of sterilization: When formulations are meant for parenteral and ophthalmic use, size reduction should be conducted in a sterile environment. The equipment should be sterilizable. Ball mill and fluid energy mills are suitable for this purpose. Contamination of milled material: In case of potent drugs and low products, contamination of the product should be avoided. Use of equipment that is free from wearing of milling parts is preferred. Fluid energy mill is advisable for this purpose. 43

44. Factors related to safety and economy: The factors related to safety are explosivity, irritability and toxicity. During milling, fine dust of drug arises which may become flammable under certain conditions. Moreover the dust of drug is inhaled by the workers operating the mill which is not desirable if the drug is toxic. Problems related to explosion hazards of non-metallic materials, such as sulphur, starch and wood floor are often appreciable. Metal powders pose a hazard because of their flammability. The useful precautions are: Isolation of the mill Use of non-sparking material of construction. Stainless steel has less sparking tendency than ordinary steel. Cost, power consumption, space required and labour costs are some of the economic factors that determine selection of a mill. When the particle size control is not critical, the cost decides the type the equipment. In general, as the particle size decreases, the cost of the size reduction increses. Therefore, it is economically undesirable to reduce the particle size to a finer degree than necessary. 44

45. Points to remember Size reduction is a process of reducing large solid unit masses (example vegetable or chemical substances) into small unit masses. Size reduction process is also referred to as Comminution, Pulverization and Grinding. Size reduction has the advantage of increased absorption, effective mixing, effective extraction and enhances the physical appearance and stability of formulations Size reduction is carried out by cutting, compression, impact and attrition. Finest particle size is produced by the attrition process. Any material undergoes grinding when the stresses on the material exceeds the elastic limit A size reduction equipment consists of hopper, milling chamber and the discharge chute as the essential parts. A hammer mill consists of 4-6 hammers which beats the material to grind it. Ball mill consists of a hollow cylinder filled with balls which acts as the grinding medium. It is a noisy machine. Fluid energy produces ultra -fine powder. Edge runner and end runner mills grind the material by compression. Size reduction is influenced by factors related to nature of the material, nature of finished product, safety and economy of the process. 45

46. Question bank REVIEW QUESTIONS VERY SHORT ANSWER TYPE (2 MARKS EACH): Define Size reduction. Enlist modes of stress applied in size reduction. Define cutting and compression mechanism of size reduction. What are the objectives of size reduction? What are the drawbacks of size reduction? Define Impact and attrition mechanism of size reduction. Define Rittingers and kick’s law of grinding. Define kick’s and Bond’s law of size reduction. Size reduction of a material enhances the action of drugs. Explain it. How does stickiness affect the process of size reduction? How does the presence of moisture interfere with the process of Size reduction? In a hammer mill, the particle size of the powder is far less than the mesh size of the screen. Why? Fluid energy mill is better equipment for size reduction of thermolabile substances compared to hammer mill. Explain. Fluid energy mill is meant for wet grinding. True or False. Explain. What is the effect of speed on ball mill efficiency? Draw a well labeled diagram of fluid energy mill. Draw a well labeled diagram of Edge runner mill. What is the principle of fluid energy mill? What are the demerits of ball mill? Which are the parameters that regulate the fineness of the product in hammer mill? What are the uses of fluid energy mill?   46

47. Question bank REVIEW QUESTIONS SHORT ANSWER TYPE (5 MARKS EACH): Explain the factors related to nature of raw materials influencing size reduction. Explain construction and working of hammer mill. Explain construction and working of ball mill. Define Size reduction. Explain the mechanisms of size reduction. Expain laws governing size reduction. Explain construction and working of fluid energy mill. Explain construction and working of edge runner mill. Explain the objectives of size reduction. Draw well labeled diagram of fluid energy mill. What are its demerits? Describe an end runner mill. 47

48. Question bank REVIEW QUESTIONS LONG ANSWER TYPE (10 MARKS): 1. Explain the factors influencing size reduction. 2. Explain the advantages and disadvantages of size reduction. 3.Enlist mechanism of size reduction. Discuss the principle, construction, working advantages and disadvantages of fluid energy mill. 4. Discuss the principle, construction, working ,advantages and disadvantages of ball mill. 5.Describe a mill which works on the principle of combined impact and attrition. 6. Discuss edge runner and end runner mill. 7. Discuss the principle, construction, working , merits and demerits of hammer mill. 48