1. PH 101.241 Objective (i)What is size reduction (ii)Importance of size reduction & its application (iii)Methods of size reduction.

2. PH 101.242 Identify this Fig: 24.1 Mixie

3. PH 101.243 Fig: 24.2 chopper Fig: 24.3 mortar& pestle

4. PH 101.244 Size Reduction I.What do you understand when I say size reduction related to Pharmacy? a. Definition : Size Reduction or Comminution means reducing drugs (vegetable and chemical substances) into smaller, coarser or fine particles.

5. PH 101.245 II. Can you give some examples as to how we employ size reduction in daily life a.Cutting b.Chopping c.Crushing d.Grinding e.Milling f.Micronizing g.Trituration

6. PH 101.246 III. Can you classify the equipments or instruments which are closely related to the above methods. Table : 1 classification of Size reduction Equipment Small Scale Large Scale a.Cutting - KnifeCutter Mill b.Chopping - AxeOnion Cutter c.Crushing - Hammer (Sutthi) Hammer Mill d.Grinding - Hand Grinder Disintegrator, Mixie (Vissur Rayee) e.Milling - Mortar & PestleMilling Machine (Rolu & Rokali) (Flour Mill) f. Micronizing - -- Fluid Energy Mill or Jet Mill or Micronizer

7. PH 101.247 Physical & Chemical characteristics of the material Specifications of the final product The economics of the process The performance of the equipment IV. The selection of grinding and milling machinery depends on:

8. PH 101.248 V. Each instrument or equipment works on a particular principle or stress (action) Can you mention and define them if not let us get familiar with these terms

9. PH 101.249 1.Impact : The act of one body striking another or the force with which one thing hits another. Fig : 24.4 Mechanism of impact

10. PH 101.2410 2.Attrition : In this method due to rubbing action of two surfaces which are moving relative to each other, resulting in shear forces, the particle size is reduced. Fig:24.5. mechanism of attrition

11. PH 101.2411 3.Cutting : The material is cut on a small scale by means of a sharp blade, knife, root cutter or any other sharp instrument ; cutter mill is used on large scale. Fig:24.6. mechanism of cutting

12. PH 101.2412 4.Compression or Rolling : In this method the material is crushed by application of pressure between two rollers. Fig:24.7 mechanism of compression

13. PH 101.2413 5.Shearing : When the material is passing through the stationery and rotating discs due to shear force, the size is reduced (Colloid Mill). Fig:24.8. colloid millFig:24.9. straight blunt mill

14. PH 101.2414 General Characteristics of various types of mills S No Name of the Mill Principle / Action Product Size UsesNot suitable 1Cutter MillCutting20 – 80 mesh Fibrous,crude(animal& vegetable drug) Friable material 2Roller MillCompre- ssion 20–200 mesh Soft materialAbrasive material 3Hammer Mill (Swing type) Impact4 – 325 mesh Almost all drugsAbrasive material 4DisintegratorImpact20 – 80 mesh Almost all drugs including very hard drugs Soft & Sticky mat. 5Ball MillAttrition & Impact 20–200 mesh Brittle drugsSoft material 6Micronizer / Fluid energy mill Attrition & Impact 1 – 30 µmModerately hard & friable material Soft & Sticky mat. 7Edge runner mill & End runner mill Crushing& Shearing 20 – 80 mesh Almost all drugsSticky material Table: 2

15. PH 101.2515 Objectives The objectives of size reduction. Disadvantages of size reduction. Factors that affect the size reduction.

16. PH 101.2516 Advantages & Importance of Size reduction (i)It improves appearance. (ii)It increases surface area. (iii)It facilitates absorption and bio-availability. (iv)It improves the stability (suspension, emulsion). Contd..

17. PH 101.2517 Stoke’s Law – V  d 2 (S s – S 1 ) g ------------------ 18 η Where V = Velocity of globule d = Radius of globule S s = Specific Gravity of the dispersed phase S 1 = Specific Gravity of the continuous phase η = Viscosity of the continuous phase g = Gravity constant Contd..

18. PH 101.2518 As size of oil droplets in emulsion decreases the rate of creaming decreases. In Case of suspension, when particle size decreases, rate of sedimentation decreases. (v)It facilitates extraction. (vi)It facilitate mixing. (vii)In aerosol and inhalation preparations. (viii)Parental suspension.

19. PH 101.2519 (v)It facilitate drying. (vi)Opthalmic Suspension. (vii)Increase in Viscosity. (viii)Change of color. (ix)Sustained action of dosage form depend upon particle size. (x)Upon size reduction, bulkiness increases.

20. PH 101.2520 Disadvantages Loss of Aromatic Principles. Leading agglomeration. Change in polymorphic form. Degradation of drugs. Problem of preservation

21. PH 101.2521 Factors which affect size reduction Hardness Toughness Stickiness Slipperiness Abrasiveness Temperature

22. PH 101.2522 Factors which affect size reduction Ratio of feed size to product size Bulk density Potency or toxicity / physiological effects Purity required Material structure

23. PH 101.2523 Selection of degree of size reduction of material. Use of powder after its size reduction Because smaller the particle size costlier the size reduction process.

24. PH 101.2524 The basic principles governing the selection of degree of size reduction are as follows : Drugs which are to be reduced in fine powder Administered in the form of powders and suspension in mixtures. To be injected in suspension form. To be extracted depending on the following factors. Solvent or menstrum eg. Water or Alcohol. Drug / Menstrum ratio. Physical character of drug and localization of active constituents. Method of Process used.

25. PH 101.2625 Manual methods used in size reduction Trituration Pulverization by intervention Levigation Hammer mill Objective

26. PH 101.2626 Manual Methods and equipment (Small Scale Procedures) Common operations once used in Pharmacy are rarely employed by the community: Cutting Chopping Rasping Grating etc., Have been replaced by Mortar and Pestle, Spatula with which most communition and mixing procedures are presently conducted.

27. PH 101.2627 Manually operated procedures employed by prescription pharmacists today are Trituration Pulverization by intervention Levigation Fig : 26.1 Mortar & pestle

28. PH 101.2628 Trituration Refers to the process of reducing substances to fine particles by rubbing in a mortar and pestle. Also designates whereby a mixture of fine powders is intimately mixed in a mortar The circular mixing motion of the pestle on the powders contained in a mortar results in blending them and in also breaking up soft aggregates of powders

29. PH 101.2629 By means of application of pestle on the mortar, crushing, grinding also can be effected. When granular or crystalline materials are to be incorporated into powdered product, these material are comminuted individually and then blended together in the mortar. Trituration

30. PH 101.2630 Pulverization By Intervention Method of powdering to a fine state with a help of another substance (Liquid) which can be easily removed at the end of the process Eg: Camphor (Alcohol) Iodine crystals (ether)

31. PH 101.2631 Levigation Is a process of wet grinding. Where a substance is reduced to an extremely fine state of sub-division. By rubbing in a glass mortar or on a slab with the help of a liquid in which it is insoluble. The liquid being called the levigating agent.

32. PH 101.2632 Selected on the basis of its incompatibility with the product. Eg: Chalk, kaolin (light), calamine and camphor etc. Water cannot be used as a levigating agent with zinc oxide intended to be incorporated into an oleaginous ointment base. Light liquid paraffin is the levigating agent of choice in this state. Levigation

33. PH 101.2633 Discuss about: Principle, construction, working, advantages, disadvantages, applications of each mill.

34. PH 101.2634 As summarized in this table SNoSNo Name of the MillPrinciple / Action Product Size UsesNot suitable 1Cutter MillCutting20 – 80 mesh Fibrous, crude (animal & vegetable drug) Friable material 2Roller MillCompre- ssion 20–200 mesh Soft materialAbrasive material 3Hammer Mill (Swing type) Impact4 – 325 mesh Almost all drugsAbrasive material 4DisintegratorImpact20 – 80 mesh Almost all drugs including very hard drugs Soft & Sticky mat. 5Ball MillAttrition & Impact 20–200 mesh Brittle drugsSoft material 6Micronizer / Fluid energy mill Attrition & Impact 1 – 30 µm Moderately hard & friable material Soft & Sticky mat. 7Edge runner mill & End runner mill Crushing & S hearing 20 – 80 mesh Almost all drugsSticky material Table:1

35. PH 101.2635 Hammer Mill Principle : impact Fig: 26.2 schematic diagram hammer mill

36. PH 101.2636 Principle : impact Fig: 26.3 Different types of hammer mills

37. PH 101.2637 Fig : 26.4 Principal of Hammer mill

38. PH 101.2638 Fig:26.5. Star hammer mill

39. PH 101.2639 Fig: 26.6 Different types of Fitzmil screens

40. PH 101.2640 Hammer Mill Rigidly mounted Mounted with Swivel joints DisintegratorHammer mill

41. PH 101.2641 Construction Stout metal casing (S.S) may be undulated to increase efficiency. Hammers 4 or more attached to central shaft. Mounted with swivel joints, so that they swing out to radial position when shaft is rotated.

42. PH 101.2642 Can rotate horizontally / vertically / based on rotar configuration. On upper part or centre of the casing is the feed hopper. On lower part of casing, screen (sieve) of desired size is fitted; it is replaceable. Construction

43. PH 101.2643 Working Material fed in grinding zone. In grinding zone, beaters revolve at very high speed (5000 – 10000 rpm). Material thrown out centrifugally and ground by impact of hammers or against the plates along the periphery of the mill casing. If particle size of the material (feed) is less than that of mesh size, it will pass through the sieve; oversize particles retain in the zone (recycle).

44. PH 101.2644 Applications Is versatile mill. Used for variety of materials. Wide range reduction (intermediate grades 4 – 325 #). Powdering of barks, leaves, roots, crystals and filter cakes. In preparing of wet granules for compressed tablets.

45. PH 101.2645 Advantages Rapid size reduction. Used for different types of material – dry material, wet filter press cake, ointments and slurries. The product size can be controlled by variation of : Rotor speed Hammer type and number Size of mesh Feed rate Clearance between hammers and casing Contd..

46. PH 101.2646 Simple to install and operate Easy to clean and operate as closed system Less contamination of product Operation is continuous.

47. PH 101.2647 Disadvantages High speed causing heat generation Thermolabile materials or drugs ( gum, fat or resins may be affected) If the rate of speed is not controlled, mill may be choked. Sticky material cannot be grinded as screen may get choked. Not used for abrasive material.

48. PH 101.2748 Objective Principal, construction, working, advantages, disadvantages Applications of - Disintegrator - Ball mill - Fluid energy mill.

49. PH 101.2749 The Disintegrator (Ross Beater Mill) Principle : Impact Fig: 27.1 Schematic diagram of disintegrator

50. PH 101.2750 Construction Consists of steel drum with central shaft. Shaft contains a disc with 4 fixed beaters. Speed 5000 – 7000 RPM. Inner upper surface is rough and undulating. Lower part has detachable screen (sieve) with definite pore size. Beside the milling chamber dust bag is placed for collecting the powder. Hopper directly fitted to the drum.

51. PH 101.2751 Working The material is fed to the beaters. High velocity and undulation of the inner surface facilitates the impact. Product is collected into closed receiver through the screen. The beaters rotating at very high speed developing a current inside the drum, which is allowed to pass through an outlet having a chest (dust bag) retaining the fine particles of the powder. Application : All types of drugs including very hard drugs.

52. PH 101.2752 Application: 1. All types of drugs including very hard drugs. Advantages : 1.Rapid 2.Desired product size 3.Continuous process 4.Little contamination Dis -advantages : 1.Drug should be dried before feeding which is time consuming process. 2.Due to high speed, affect thermolabile material. 3.Problem of choking.

53. PH 101.2753 Ball Mill or Pebble Mill or Pot Mill or Jar Mill Principle : Impact and Attrition. Fig: 27.2 Ball mill

54. PH 101.2754 Fig: 27.3 Sehematic Diagram of Ball Mill Ball Mill

55. PH 101.2755 Ball Mill Fig: 27.4. working of ball mill

56. PH 101.2756 Construction Ball mill consists of hallow cylinder (made up of metal (S.S), porcelain internally with rubber lined). The length of cylinder is slightly greater than its diameter. The hallow cylinder rotates on its longitudinal axis, fixed on the metallic frame. The cylinder consists of different sized iron balls, depending on the size or capacity of the cylinder. To operate effectively, material from 30 to 50% of the volume of the mill is required.

57. PH 101.2757 Working Only 60% of feed is placed in the cylinder along with the balls. The jars / drum revolve horizontally on its long axis. Balls move causing combined attrition and impact as shown in the figure and causes size reduction. Finally the product is collected by opening the cylinder lid.

58. PH 101.2758 Application Used for grinding of brittle drugs to fine powder. Used for sterile grinding.

59. PH 101.2759 Advantages It produces very fine powder (100#). It is a continuous process, if sieve and classifier attached. It can be used to grind toxic material. Economical. Ophthalmic and parental products milling can be done. A wide variety of material can be ground with different degrees of hardness. No cross contamination due to easy cleaning.

60. PH 101.2760 Disadvantages Ball mill is a very noisy machine. Wear occurs from the balls and from casing, causing contamination of the product. Abrasive material cannot be ground. It is a slow process. At low speed, the balls will slide or roll over each other and only negligible amount of size reduction will occur. At high speed, the balls will be thrown out to the wall by centrifugal force and no grinding will occur.

61. PH 101.2761 Fluid Energy Mill or Micronizer Principle : Impact and Attrition. The distinctive principle of ULTRAFINE equipment consists of introducing the material to be pulverized into an air current and thereafter submitting to : a.Intense Turbulence b.Changes of pressure c.Vibration Which progressively disintegrate the material or cause it to shatter from within (as in the case of cellular matter)

62. PH 101.2762 Construction and Function 1.It consists of a loop of pipe of diameter (20 – 200 mm) depending on the height of the loop, which may be upto 2 meters Fig: 27.5 Fluid energy mill

63. PH 101.2763 2.A fluid usually air / gas is injected at high pressure jet through nozzles at the bottom of the loop. 3.The high velocity of air (600 kilo pascals to 1.0 mega pascals compressed air) creates turbulence / a state of confusion, movement or agitation, into which the solid particles are fed (solid inlet). 4.The impact and some attrition that is developed due to high kinetic energy of the air in the elliptical loop helps in the fracture of the particles. 5.A particle size classifier / filter is fixed in the mill to allow only those particles, which are sufficiently reduced. Construction and Function

64. PH 101.2764 Application: Used whenever fine powders are required as in drugs like antibiotics, sulphonamides and vitamins.

65. PH 101.2765 Advantages : 1.A maximum degree of size reduction occurs with this mill. 2.Useful for milling thermolabile drugs. 3.Contamination is not possible. Dis -advantages : 1.The feed should be pre-treated to reduce the particle size to the order of 100 mesh. 2.Skilled operators have to be employed. 3.It is expensive. 4.Soft, tacky and fibrous material cannot be milled.