BP304T PHARMACEUTICAL ENGINEERING, UNIT-1.pptx

pharmaceutical eng

1. B. Pharmacy III Semester P harmaceutical Engineering BP304T Mr. Ayushmaan Roy Assistant Professor Department of Pharmacy Kalinga University Naya Raipur (C.G.), India

2. COURSE OBJECTIVE Upon completion of the unit student shall be able : Different ways to measure the pressure and their machinery instrumentation. Study the different materials used in the pharmaceutical plant constructions. Emphasize principles, mechanisms and theories of different unit operations. COURSE OUTCOME BP304T-PHARMACEUTICAL ENGINEERING 2 This course is of various unit operations used in pharmaceutical industry designed to impart a fundamental knowledge on the art and science.

3. CONTENTS CLASS NAME- B.Pharmacy Semester- 3 rd sem Paper Code – BP304T SUBJECT NAME-Pharmaceutical Engineering S.No. Unit Name /Topic 1 Fluid properties Reynolds experiment , Manometer Orificemeter 2 Rotameter Current flow meter 3 Size reduction Factors principles and applications 4 Apparatus used in size reduction like ball mill, hammer mill 5 Size seperation Apparatus used in the seperation process BP304T-PHARMACEUTICAL ENGINEERING 3

4. CONTENTS Fluid properties Reynolds experiment , Manometer Orificemeter Venturimeter , Pitot tube Rotameter Current flow meter Size reduction Factors principles and applications Apparatus used in size reduction like ball mill, hammer mill Size seperation Apparatus used in the seperation process BP304T-PHARMACEUTICAL ENGINEERING 4

5. REFERENCES/TEXT BOOKS Introduction to chemical engineering – Walter L Badger & Julius Banchero , Latest edition. Solid phase extraction, Principles, techniques and applications by Nigel J.K. Simpson- Latest edition. Unit operation of chemical engineering – Mcabe Smith, Latest edition. Pharmaceutical engineering principles and practices – C.V.S Subrahmanyam et al., Latest edition. Remington practice of pharmacy- Martin, Latest edition. Theory and practice of industrial pharmacy by Lachmann ., Latest edition. Physical pharmaceutics- C.V.S Subrahmanyam et al., Latest edition. Cooper and Gunn’s Tutorial pharmacy, S.J. Carter, Latest edition BP304T-PHARMACEUTICAL ENGINEERING 5

6. LECTURE PLAN Lecture No . Topics to be covered Slide No. L-1 Flow of fluids: Types of manometers 10-17 L-2 Reynolds number and its significance, Bernoulli’s theorem and its applications, Energy losses, Orifice meter, 18-30 L-3 manometers 31-55 L-4 ·Size Reduction: Objectives, Mechanisms & Laws governing size reduction, factors affecting size reduction, 56-70 L-5 principles, construction, working, uses, merits and demerits of Hammer mill, ball mil 71-82 L-6 fluid energy mil 83-96 L-7 Size Separation: Objectives, applications & mechanism of size separation, official standards of powders, sieves, 97-105 L-8 Principles, construction, working, uses, merits and demerits of Sieve shake 106-110 9 cyclone separator, Air separator, 111-115 Quiz 20 mcqs with answers 116-126 answers BP304T-PHARMACEUTICAL ENGINEERING 6

7. UNIT 1 BP304T-PHARMACEUTICAL ENGINEERING 7

8. FLUID FLOW A fluid is a substance that continually deforms (flows) under an applied shear stress. Fluids are a subset of the phases of matter and include liquids, gases both. Fluid flow may be defined as the flow of substances that do not permanently resist distortion. The subject of fluid flow can be divided into fluid statics and fluid dynamics. Identification of type of flow is important in Manufacture of dosage forms Handling of drugs for administration 8 BP304T-PHARMACEUTICAL ENGINEERING

9. FLUID STATICS Fluid statics deals with the fluids at rest in equilibrium, Behavior of liquid at rest Nature of pressure it exerts and the variation of pressure at different layers Pressure differences between layers of liquids h1 h2 Point 1 Point 2 9 9 BP304T-PHARMACEUTICAL ENGINEERING

10. Consider a column of liquid with two openings Which are provided at the wall of the vessel at different height The rate of flow through these opening s are different due to the pressure exerted at the different height Consider a stationary column the pressure p s is acting on the surface of the fluid, column is maintained at constant pressure by applying pressure The force acting below and above the point 1 are evaluated Substituting the force with pressure x area of cross section in the above equation Force acting on the liquid At point 1 = Force on the surface + Force excreted by the liquid 10 Above point 1 Pressure at point 1 x Area = Pressure on the surface x area + mass x acceleration 10 BP304T-PHARMACEUTICAL ENGINEERING

11. 11 P 1 S = P s S + volume x density x acceleration = P s S + height x area x density x acceleration P 1 S = P s S + h 1 S ρ g Since surface area is same P 1 = P s + h 1 ρ g Pressure acting on point 2 may be written as P 2 = P s + h 2 ρ g Difference in the pressure is obtained by P 2 - P 1 = g (P s + h 2 ρ ) – ( P s + h 1 ρ) g ∆P = ( P s + h 2 ρ – P s - h 1 ρ ) g = ∆ h ρ g 11 BP304T-PHARMACEUTICAL ENGINEERING

12. FLUID DYNAMICS Fluid dynamics deals with the study of fluids in motion This knowledge is important for liquids, gels, ointments which will change their flow behavior when exposed to different stress conditions MIXING FLOW THROUGH PIPES FILLED IN CONTAINER 12 12 BP304T-PHARMACEUTICAL ENGINEERING

13. The flow of fluid through a closed channel can be viscous or turbulent and it can be observed by; Reynolds experiment Consider Glass tube which is connected to reservoir of water, rate of flow of water is adjusted by a valve, a reservoir of colored solution is connected to one end of the glass tube with help of nozzle colored solution is introduced into the nozzle as fine stream. 13 13 BP304T-PHARMACEUTICAL ENGINEERING

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15. 15  Laminar flow is one in which the fluid particles move in layers or laminar with one layer sliding with other.  There is no exchange of fluid particles from one layer to other.  When velocity of the water is increased the thread of the colored water disappears and mass of the water gets uniformly colored, indicates complete mixing of the solution and the flow of the fluid is called as turbulent flow.  The velocity at which the fluid changes from laminar flow to turbulent flow that velocity is called as critical velocity . 15 BP304T-PHARMACEUTICAL ENGINEERING

16. REYNOLDS NUMBER In Reynolds experiment the flow conditions are affected by Diameter of pipe Average velocity Density of liquid Viscosity of the fluid This four factors are combined in one way as Reynolds number Reynolds number is obtained by the following equation D u ρ η Inertial forces are due to mass and the velocity of the fluid particles trying to diffuse the fluid particles viscous force if the frictional force due to the viscosity of the fluid which make the motion of the fluid in parallel INERTIAL FORCES = - - ---- - -- -- --- -- -- -- --- -- --- -- = VISCOUS FORCES MASS X ACCELERATION OF LIQUID FLOWING ---------------------------------------------------------- SHEAR STRESS X AREA 10 16 BP304T-PHARMACEUTICAL ENGINEERING

17. 17 If Re < 2000 the flow is said to be laminar If Re > 4000 the flow is said to be turbulent If Re lies between 2000 to 4000 the flow change between laminar to turbulent APPLICATIONS Reynolds number is used to predict the nature of the flow Stocks law equation is modified to include Reynolds number to study the rate of sedimentation in suspension BP304T-PHARMACEUTICAL ENGINEERING

18. BERNOULLI'S THEOREM When the principals of the law of conservation energy is applied to the flow of the fluids the resulting equation is called Bernoulli's theorem Consider a pump working under isothermal conditions between points A and B as shown in figure; 18 BP304T-PHARMACEUTICAL ENGINEERING

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20. 20 At point a one kilogram of liquid is assumed to be entering at this point, pressure energy at joule can be written as Pre s s u re ene r gy = P a /g ρ A Where P a = Pressure at point a g = Acceleration due to gravity ρ A = Den s ity of the liquid Potential energy of a body is defined as the energy possessed by the body by the virtue of its position or configuration Potential energy = X A Kinetic energy of a body is defined as the energy possessed by the body by virtue of its motion, kinetic energy = U A / 2g 2 Total energy at point A = Pressure energy + Potential energy+ Kinetic energy BP304T-PHARMACEUTICAL ENGINEERING

21. 21 Total energy at point A = P a /g ρ A + X A + U A / 2g 2 According to the Bernoulli's theorem the total energy at point A is constant Total energy at point A = P a /g ρ A +X A + U A / 2g = Constant 2 After the system reaches the steady state, whenever one kilogram of liquid enters at point A, another one kilogram of liquid leaves at point B Total energy at point B = P B /g ρ B + X B + U B / 2g 2 INPOUT = OUT PUT P a /g ρ A + X A + U 2 / 2g = P B /g ρ B + X B + U 2 / 2g A B Theoretically all kids of the energies involved in fluid flow should be accounted, pump has added certain amount of energy Energy added by the pump = + wJ BP304T-PHARMACEUTICAL ENGINEERING

22. 22 During the transport some energy is converted to heat due to frictional Forces Loss of energy due to friction in the line = FJ A B P a /g ρ A + X A + U 2 / 2g – F + W = P B /g ρ B + X B + U 2 / 2g This equation is called as Bernoulli's equation Application Used in the measurement of rate of fluid flow It applied in the working of the centrifugal pump, in this kinetic energy is converted in to pressure BP304T-PHARMACEUTICAL ENGINEERING

23. 23 ENERGY LOSS According to the law of conversation of energy ,energy balance have to be properly calculated fluids experiences energy losses in several ways while flowing through pipes, they are Frictional losses Losses in the fitting Enlargement losses Contraction losses BP304T-PHARMACEUTICAL ENGINEERING

24. 24 FRICTIONAL LOSSES During flow of fluids frictional forces causes a loss in pressure Type of fluid flow also influences the losses In general pressure drop will be PRESS URE DROP α VE L OCI T Y (u) α Density of fluid( ρ) α Length of the pipe (L) α 1 / diameter of the pipe (D) These relationships are proposed in Fanning equation for calculating friction losses Fa n n i ng e q u a tion ∆p = 2 f u 2 L ρ / D F = frictional factor For viscous flow pressure drop Hagen –Poiseullie equation = 32 Luη / D 2 BP304T-PHARMACEUTICAL ENGINEERING

25. LOSSES IN FITTING Fanning equation is applicable for the losses in straight pipe When fitting are introduced into a straight pipe, They cause disturbance in the flow, Which result in the additional loss of energy losses in fitting may be due to Change in direction Change in the type of fittings Equivalent length of fitting = Equivalent length x internal diameter For globe valve = 300 x 50 = 15 meter That means globe valve is equal to 15 meters straight line, so this length is substituted in fanning equation Tee fitting Equivalent length = 90 Globe valve equivalent length = 300 25 BP304T-PHARMACEUTICAL ENGINEERING

26. ENLARGEMENT LOSS If the cross section of the pipe enlarges gradually, the fluid adapts itself to the changed section with out any disturbance So no loss of energy If the cross section of the pipe changes suddenly then loss in energy is observed due to eddies These are greater at this point than straight line pipe Than u 2 < u 1 For sudden enlargement = ∆ H = (u 1 – u 2 ) 2 / 2g ∆ H = loss of head due to sudden enlargement µ1 µ2 µ1 26 µ2 BP304T-PHARMACEUTICAL ENGINEERING

27. CONTRACTION LOSSES If the cross section of the pipe is reduced suddenly the fluid flow is disturbed, the diameter of the fluid stream is less than the initial value of diameter this point of minimum cross section is known as vena contracta. the velocity of fluid at smaller cross section will be greater than at larger cross section , u 2 > u 1 27 BP304T-PHARMACEUTICAL ENGINEERING

28. 28 MANOMETERS Manometers are the devices used for measuring the pressure difference Different type of manometers are; Simple manometer Differential manometer Inclined manometer BP304T-PHARMACEUTICAL ENGINEERING

29. 29 SIMPLE MANOMETER This manometer is the most commonly used one It consists of a glass U shaped tube filled with a liquid A- of density ρ A kg /meter cube and above A the arms are filled with liquid B of densi t y ρ B . The liquid A and B are immiscible and the interference can be seen clearly If two different pressures are applied on the two arms the meniscus of the one liquid will be higher than the other Let pressure at point 1 will be P1 Pascal's and point 5 will be P2 Pascal's The pressure at point 2 can be written as = P 1 + (m + R ) ρ B g (m + R ) = distance from 3 to 5 BP304T-PHARMACEUTICAL ENGINEERING

30. P1 P2 m R 1 30 2 3 4 5 L i q u id A LIQUID B BP304T-PHARMACEUTICAL ENGINEERING

31. 31 Since the points 2 and 3 are at same height the pressure at 3 can be written as Pre s s u re at 3 = P 1 + (m + R ) ρ B g Pressure at 4 can be written as = P 2 + gm ρ B or = P 1 + ρ B ( m + R ) g- ρ a R g Both the equations should be equal P 2 + gm ρ B = P 1 + ρ B ( m + R ) g- ρ a R g P 1 – P 2 = g m ρ B - ρ B ( m + R ) g + ρ A R g ∆P = gm ρ B - gm ρ B - R ρ B g + R ρ A =R ( ρ A - ρ B )g BP304T-PHARMACEUTICAL ENGINEERING

32. 32 DIFFERENTIAL MANOMETERS These manometers are suitable for measurement of small pressure differences It is also known as two – Fluid U- tube manometer It contains two immiscible liquids A and B having nearly same densities The U tube contains of enlarged chambers on both limbs, Using the principle of simple manometer the pressure differences can be written as ∆P =P 1 –P 2 =R ( ρ c – ρ A ) g BP304T-PHARMACEUTICAL ENGINEERING

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34. 34 INCLINED TUBE MANOMETERS Many applications require accurate measurement of low pressure such as drafts and very low differentials, primarily in air and gas installations In these applications the manometer is arranged with the indicating tube inclined, as in Figure, therefore providing an expanded scale This enables the measurement of small pressure changes with increased accuracy P 1 –P 2 = g R ( ρ A - ρ B ) sin α BP304T-PHARMACEUTICAL ENGINEERING

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36. 36 MEASUREMENT OF RATE OF FLOW OF FLUIDS When ever fluid are used in a process it is necessary to measure the rate at which the fluid is flowing through the pipe , Methods of measurement are Direct weighing or measuring Hydrodynamic methods Orifice meter Venturi meter Pitot meter Rotameter Direct displacement meter BP304T-PHARMACEUTICAL ENGINEERING

37. 37 DIRECT WEIGHING OR MEASURING The liquid flowing through a pipe is collected for specific period at any point and weighed or measured, and the rate of flow can be determined. Gases can not be determined by this method. ORIFICE METER Principle: Orifice meter is a thin plate containing a narrow and sharp aperture When a fluid stream is allowed to pass through a narrow constriction the velocity of the fluid increase compared to up stream This results in decrease in pressure drop and the difference in the pressure may be read from a manometer The velocity of the fluid at thin constriction may be written as U =C √ 2g ∆H BP304T-PHARMACEUTICAL ENGINEERING

38. 38 ∆H = difference in height, can be measured by manometer C = constant U = velocity of fluid at the point of orifice meter CONSTRUCTION It is consider to be a thin plate containing a sharp aperture through which fluid flows Normally it is placed between long straight pipes For present discussion plate is introduced into pipe and manometer is connected at points A and B WORKING Orifice meter is referred as the variable head meter, ie it measure the variation in the pressure across a fixed construction placed in the path of flow BP304T-PHARMACEUTICAL ENGINEERING

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40. 40 When fluid is allowed to pass through the orifice the velocity of the fluid at point B increase, as a result at point A pressure will be increased Difference in the pressure is measured by manometer Bernoulli's equation is applied to point A and point B for experimental conditions √ µ 2 – µ 2 =C √2g ∆H A 0 µ = velocity of fluid at orifice µ A = velocity of fluid at point A C = constant If the diameter of the orifice is 1/5 or less of the pipe diameter then µ A is neglected so, Applications µ = C √2g ∆H Velocity at either of the point A and B can be measured Volume of liquid flowing per hour can be determined BP304T-PHARMACEUTICAL ENGINEERING

41. 41 VENTURI METER Principle: Venturi meter consist of two tapered sections in the pipe line with a gradual constriction at its centre. When fluid stream is allowed to pass through the narrow throat the velocity of the fluid increases at the venturi compared to velocity of the upstream. This results in decrease in the pressure head. This resulting decrease in the pressure head is measured directly from the manometer. BP304T-PHARMACEUTICAL ENGINEERING

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45. 45 Disadvantages Expensive Need technical expert Not flexible Occupies more space Advantages Power loss is less Head loss is negligible Applications: It is commonly used for liquids, specially for water. It can also be used for the measurement of gases. BP304T-PHARMACEUTICAL ENGINEERING

46. 46 PITOT TUBE Principle: Pitot tube consists of sensing element with a small constriction compared to the size of the flow channel. When the sensing element is inserted at the center of the stream, the velocity of flow is increased . This results in decrease in pressure head . ∆H p = u 2 /2g BP304T-PHARMACEUTICAL ENGINEERING

47. PITOT TUBE 47 BP304T-PHARMACEUTICAL ENGINEERING

48. 48 C o nstruction It is also known as insertion meter or insertion tube The size of the sensing element is small compared to the flow channel The point of measurement may be at the center of the channel One tube is perpendicular to the flow direction and the other is parallel to the flow Two tubes are connected to the manometer Working Tube are inserted in the flow shown is the figure. Pitot tube is used to measure the velocity head of the flow. In this tube velocity of fluid is increased at the narrow constriction which results in decreased pressure. BP304T-PHARMACEUTICAL ENGINEERING

49. Tube at right angles to the flow measures pressure head only while the tube that points upstream measures pressure head and velocity head. µ 2 = C v √2g ∆H C v coefficient of Pitot tube 49 BP304T-PHARMACEUTICAL ENGINEERING

50. 50 ROTAMETER Principle: Rotameter is known as area meter as it measures area of flow. It consist of a vertical, tapered and transparent tube in which plummet is placed. During the fluid flow through the tube the plummet rises and falls because of variation of flow. BP304T-PHARMACEUTICAL ENGINEERING

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52. Construction It consists of vertically tapered and transparent tube with narrow end down, in which a plummet is placed. A solid plummet is placed in the tube. The diameter of the plummet is smaller than the narrowest part of the tube. Floats/plummet is made up of glass, aluminium or plastic. The tube is usually made of glass on which linear scale is given. During the flow the plummet rise due to variation in flow The upper edge of the plummet is used as an index to note the reading 52 BP304T-PHARMACEUTICAL ENGINEERING

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54. SIZE REDUCTION BP304T-PHARMACEUTICAL ENGINEERING 54

55. D EFINITION: SIZE REDUCTION 55 Size reduction is the operation carried out for reducing the size of bigger particles into smaller one of desired size and shape with the help of external forces. COMMINUTION is another term used for size reduction. 55 BP304T-PHARMACEUTICAL ENGINEERING

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57. O BJECTIVES OF SIZE REDUCTION : Increase the surface area because, in most reactions involving solid particles, the rate of reactions is directly proportional to the area of contact with a second phase. Break a material into very small particles in order to separate the valuable amongst the two constituents. Achieve intimate mixing. To dispose solid wastes easily . To improve the handling characteristics. To mix solid particle more intimately. 4 57 BP304T-PHARMACEUTICAL ENGINEERING

58. ADVANTAGES: 58 Content uniformity Uniform flow Effective drying Increases surface area or viscosity Uniform mixing and drying Im p r o ve r a te o f a b s o r p ti o n . particles greater is absorption. Improve dissolution rate. Small e r the 58 BP304T-PHARMACEUTICAL ENGINEERING

59. D ISADVANTAGES : 59 Drug degradation Contamination 59 BP304T-PHARMACEUTICAL ENGINEERING

60. MECHANISM OF SIZE REDUCTION : Impact- particle size reduced by a single rigid force (hammer). Compression- in this mode material is crushed between rollers by the application of pressure. Attrition- arising from particles scraping a g a i n s t on e a n o th e r o r a g a i n s t a ri g id surface by rubbing action. Cutt i n g - the m a t e ri a l is cu t b y me a ns of sharp blades. 7 60 BP304T-PHARMACEUTICAL ENGINEERING

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62. MECHANISMS AND LAWS 62 The energy requirement for particle size reduction is a function of input and output of particle size, hardness, strength and other properties of solids. V ar i ous th e or i es are:- Rittinger’s theory Kick’s theory Bond’s theory for energy re q ui r em e nt BP304T-PHARMACEUTICAL ENGINEERING

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64. Integrating equation (1), E = C ln ( d i / d n ) . . . . (2 ) ( d i /d n ) = r ed u c t i o n ra ti o . I f n = 1 . e q u ati o n (2) b ec o m e s K i ck’ s t h e o r y . I f n = 1 . 5 e q u ati o n (2 ) b ec o m e s B o nd’ s t h e o r y . If n=2.0 equation (2) becomes Rittinger’s theory. 64 BP304T-PHARMACEUTICAL ENGINEERING

65. RITTINGER ’ S THEORY 13 • E= amount of energy Acc o r d i n g to th i s th e o r y energ y E r e q u ir e d for s i ze r e d u c t i o n o f u n it ma s s is d i r e c t ly a r ea p r o p o r ti o n a l to the ne w s u rf a ce produced. E=K R (Sn – Si) …. (3) Where S i = initial surface area S n = new specific surface area K R = Rittinger’s constant. 65 BP304T-PHARMACEUTICAL ENGINEERING

66. BOND ’ S THEORY According to bond theory the energy used in crack propagation is proportional to the new crack length produced. It states that energy required for deforming a set of particle of equivalent shape is proportional to the change in particle dimensions. 14 66 BP304T-PHARMACEUTICAL ENGINEERING

67. KICK ’ S THEORY : It states that energy required for deforming a set of particle of equivalent shape is proportional to the ratio of the change in particle size. 67 BP304T-PHARMACEUTICAL ENGINEERING

68. Ritti n g er ’ s t h eo r y : ( n= 2 .0 ) E n e r g y α ne w s u r f a c e a r e a f o r me d . B o n d’ s t h eo r y: ( n=1. 5 ) Energy used in crack propagation α Crack length produced. E n e r g y α R a ti o o f cha ng e i n pa rtic l e dimensions. Kick’s theory:(n=1.0) E n er g y α R a ti o o f c h an g e i n si z e . 16 68 BP304T-PHARMACEUTICAL ENGINEERING

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70. CONSTRUCTION & WORKING 70 A hammer mil is essential y a steel drum containing a vertical or horizontal rotating shaft or drum on w hi c h hamme r s a r e moun t e d . The hammers swings on the ends or fixed to the central rotor. T h e r o t o r i s r o t a t e s a t a h i g h s p ee d in s id e t h e drum while material is fed into a feed hopper. T h e m a t e r i a l i s p u t i n t o t h e hoppe r w h i c h is c onne c t e d w i t h t h e d r u m . T h e m a t e ri a l i s p o w de re d t o t h e de s i re d s i z e due to fast rotation of hammers and is c o l e c t e d unde r t h e sc r ee n . BP304T-PHARMACEUTICAL ENGINEERING

71. T h is are m a i n l y o p e r a t ed at 250 rp m or 100 t o 2500 rpm f o r the reduction of the large parti c les . speed si z ed High rotor uses 10000 rpm speed. 71 BP304T-PHARMACEUTICAL ENGINEERING

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73. ADVANTAGES : It is rapid in action, and is capable of grinding many di f f eren t t ype s o f m a t erial s . T he y ar e e as y t o i ns t a l an d ope r ate , t h e operatio n is continuous. There is little contamination of the product with m e t a l abrade d f ro m t h e m i l a s n o su r f a c e m ov e aga i ns t eac h o t he r . Th e par t i cl e s i z e o f t h e m at e r i a l t o b e reduce d can be easily control ed by changing the speed of the rotor, hammer type, shape and size of the screen. 21 73 BP304T-PHARMACEUTICAL ENGINEERING

74. DISADVANTAGES : Heat buildup during milling is more, produc t degradatio n i s poss i b l e . therefore, Hammer mills cannot be employed to mill sticky, fi brou s an d har d m aterial s . T h e sc reen s m a y ge t clogge d . 22 74 BP304T-PHARMACEUTICAL ENGINEERING

75. BALL MILL : These are also knows as tumbling mills or pebble mills. Principle: 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 speed the balls roll over each other attrition will be mode of action thus in the ball mill attrition and impact both mechanisms takes place. 23 75 BP304T-PHARMACEUTICAL ENGINEERING

76. Construction: It 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 higher than its diameter. The c y li n der c o nt a ins ba l l s th at occupy 30 to 50% of the mill volume. The ball size depends on the size of the feed and the di am et e r of t he mil l. Balls are made u p of s t e e l, iron o r ston e wa r e medium. and act as grinding 24 76 BP304T-PHARMACEUTICAL ENGINEERING

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78. 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. A fixed number of balls are introduced and the cylinder is closed. The mill is allowed to rotate on its longitudinal axis. The speed of rotation is very important 26 78 BP304T-PHARMACEUTICAL ENGINEERING

79. Use s : For fine grinding with a particle size of 100 to 5 mm or less. For prod u ction of op h thal m ic and pare n teral products. For mil l ing dy e s, pig m e n ts and insec t ici d es a t low speed. 27 79 BP304T-PHARMACEUTICAL ENGINEERING

80. ADVANTAGES : 80 It can produce very fine powder. Ball mill is use d f or b o th wet an d dr y g r i n d i ng processes. Toxic substances can be ground, as the cylinder is closed system. Rod or bars can also be used as grinding media. Sticky material are size reduced in ball mill, Installation, operation and labor costs are low. Since the mill is clos e d s y stem used f o r steri l e products and oxygen sensitive products. BP304T-PHARMACEUTICAL ENGINEERING

81. DISADVANTAGES : 81 The ball mill is a very noisy machine. Ball mill is a slow process. Soft, fi b r o us m a t e ri a l canno t b e mil l ed by ball mill. BP304T-PHARMACEUTICAL ENGINEERING

82. FLUID ENERGY MILL/ JET MILL/ MICRONIZERS/ ULTRAFINE GRINDERS 82 Principle: Fluid energy mill operates on the principle of impact and attrition. Milling takes place because of high velocity collisions between the suspended particles. Construction: It consist of an elliptical pipe which has a height of about 2 meters and diameter may be ranging from 20 to 200 mm. BP304T-PHARMACEUTICAL ENGINEERING

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84. The mill surface may be made up of either soft stainless steel or tough ceramics. Grinding nozzles are placed tangential and opposed to the initial flow path of a powder. Compressed air is used at 600 kilopascals to 1 megapascals. Venturi feeder is provided in the path of the airflow. An outlet with a classifier is fitted to allow the escape of air. 84 BP304T-PHARMACEUTICAL ENGINEERING

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86. Uses: To reduce the particle size of most of drugs such as antibiotics and vitamins. Advantages: It has no moving parts heat is not produced during milling. It is rapid and efficient method for reducing powder to 30 mm or less. No contamination is possible. Disadvantages: Not suitable for milling of soft, tacky and fibrous material. Equipment is expensive. 34 86 BP304T-PHARMACEUTICAL ENGINEERING

87. EDGE RUNNER MILL : Principle: The size reduction is done by crushing due to heavy weight of stones. Construction: It consist of two heavy rollers and may weigh several tons. The roller move on a bed which is made up of granite or stone. Each roller has a central shaft and revolve on its axis. The rollers are m o unted on horizo n tal sh a ft and move around the bed. 35 87 BP304T-PHARMACEUTICAL ENGINEERING

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89. WORKING : 89 The material to be ground is placed on the bed with the help of the scrapper in such a way that it comes in the path of the stone wheel. These stones revolve on its own axis and at the same time travel around the shallow stone bed. The material is ground for definite period. The powder is collected and passed through a sieve to get powder of required size. BP304T-PHARMACEUTICAL ENGINEERING

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91. END RUNNER MILL : Principle: Size reduction is done by crushing due to presence of heavy weight steel pestle. Construction: It is considered as mechanical mortar pestle. I t co n sist o f a s t e el mortar which is fixed t o a plate. The construction of mortar is connected to horizontal shaft bearing a pulley so the plate with mortar can be rotated at high speed. The pestle is dumb-bell shaped and bottom of pestle is flat. 39 91 BP304T-PHARMACEUTICAL ENGINEERING

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93. Construction of pestle is done in such a way that it can be raised from mortar for cleaning and emptying. 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 high speed and the pestle is placed in the mortar. The revolving mortar causes pestle to revolve. The material is collected and passed through a sieve to get the powder of desired size. 41 93 BP304T-PHARMACEUTICAL ENGINEERING

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95. SIZE SEPERATION BP304T-PHARMACEUTICAL ENGINEERING 95

96. Size Separation A s p e c i a l t e c h n i q u e i s u s e d t o s e p a r a t e p a rti c les o f sp e c i f i e d si z e w h i ch i s kn o w n a s t h e " p r o c e s s o f si z e separation". OFFICIAL STANDARDS FOR POWDERS The Indian Pharmacopoeia has laid down the standards f o r p o w d e r s f o r p h a r ma c e u ti c a l p u r p os e s . T h e I . P . specifies five grades of powder which are as under: 1. Coarse powder : A powder of which al! the particles pass through a sieve with nominal mesh aperture of 1.70 mm (No. 10 sieve) and not more than 40.0 per cent through a si e v e w it h n o m i n a l m e sh a p e r t u r e o f 35 5 u r n ( N o . 4 4 sieve) is called coarse powder. 2. Moderately coarse powder: A powder of which all the p a rti c les p a ss t h r o u g h a si e v e w it h n o m i n a l m e s h aperture of 710 nm (No. 22 sieve) and not more than 40.0 per cent through a sieve with nominal mesh aperture of 25 n m ( N o . 6 si e v e ) i s c a lle d m o d e r a t el y c o a r se powder. 2 96 BP304T-PHARMACEUTICAL ENGINEERING

97. 3. Moderately fine powder : If all the particles of a powder pass through a sieve with nominal mesh aperture of 355 µm (No. 44 sieve) and not more than 40.0 per cent through a sieve with nominal mesh aperture of 180 µm (No. 85 sieve), it falls in this group. Fine powder : In case all the particles pass through a sieve with a nominal mesh aperture of 180 µm (No. 85 sieve) , it is called fine powder, Very fine powder : If all the particles of the powder pass through a sieve with a nominal mesh aperture of 125 µm (No. 120sieve), it is said to be very fine powder. SIEVES Sieves for pharmacopoeial testing are constructed from wire cloth with square meshes, woven from wires of brass, bronze, stainless steel or any other suitable material. The wires should be of uniform circular cross-section and should not be coated or plated. There should not be any reaction between the material of the sieve and the substance which is being sifted from it. 3 97 BP304T-PHARMACEUTICAL ENGINEERING

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99. Standards for sieves used for pharmacopoeial testing must specify the following: Number of sieve : Sieve number indicates the number of meshes in a length of 2.54 cm in each transverse direction parallel to the wires. Nominal size of aperture : Nominal size of aperture indicates the distance between the wires. It represents the length of the side of the square aperture. The I.P. has given the nominal mesh aperture size for majority of sieves in mm or in cm. Nominal diameter of the wire : Wire mesh sieves are made from the wire having the specified diameter in order to give a suitable aperture size and sufficient strength to avoid distortion of the sieve. Approximate percentage sieving area : This standard expresses the area of the meshes a percentage of the total area of the sieve. It depends on the size of the wire used for any particular sieve number. Generally the sieving area is kept within the range of 35 to 40 per cent in ord 5 er to give suitable strength to the sieve. 99 BP304T-PHARMACEUTICAL ENGINEERING

100. 5. Tolerance average aperture size : Some variation in the aperture size is unavoidable and when this variation is expressed as a percentage, it is known as the 'aperture tolerance average'. SIEVING METHOD In this method, the fine powder is separated from the coarse powder by using sieves of desired number. The degree of fineness of a powder is known with the help of sieve through which the powdered material is passed. Sieves are numbered in order to distinguish from each other. Size separation of powder is done by passing the powdered material through a set of sieves. Sieves are arranged in descending order i.e. sieve of larger size is at the top and the smallest one at the bottom. The bottom sieve is attached to the receiving pan. 6 100 BP304T-PHARMACEUTICAL ENGINEERING

101. 7 101 BP304T-PHARMACEUTICAL ENGINEERING

102. 8 102 BP304T-PHARMACEUTICAL ENGINEERING

103. The material is placed in the uppermost sieve. The sieves are shaken with the help of mechanical sieve shaker or electromagnetic devices. It helps the particles to pass through the sieves. The working of mechanical sieving devices are based on any of the following methods. 1. Agitation 2. Brushing 3. Centrifugal Agitation methods Sieves may be agitated in a number of different ways, such as: Oscillation : This sieve is mounted in a frame that oscillates back and forth. It is a simple method but the material may roll on the surface of the sieve. Vibration : The sieve is vibrated at high speed by means of an electric device. The rapid vibration is imparted to the particles on the sieve which helps to pass the powdered material through it. 9 103 BP304T-PHARMACEUTICAL ENGINEERING

104. 3. Gyration : In this method, a system is made so that sieve is on rubber mounting and connected to an eccentric fly wheel. This gives a rotary movement of small amplitude to sieve which hi turn gives spinning motion to the particles that helps to pass them through a sieve. Agitation methods are not continuous methods' but can be made so by inclination of the sieve and the provision of separate outlets for undersize and oversize particles. 10 104 BP304T-PHARMACEUTICAL ENGINEERING

105. Brushing methods In this case, a brush is used to move the particles on the surface of the sieve and to keep the meshes clear. The brush is rotated in the middle in the case of a circular sieve but spiral brush is rotated on the longitudinal axis in case Of a horizontal cylindrical sieve. Centrifugal methods In this method, a high speed rotor is fixed inside the vertical cylindrical sieve, so that on rotation of rotor the particles are thrown outwards by centrifugal force. The current of air which is produced due to high speed of rotor helps in sieving the powder. On shaking the powdered material in a mechanical or electromagnetic device using any of the above methods, the weight of powder retained on each sieve is determined. The percentage of each fraction is then calculated. Sieving method is a rapid process and it requires very litt 1 l 1 e skill. The equipment used for sieving is not expensive. 105 BP304T-PHARMACEUTICAL ENGINEERING

106. CYCLONE SEPARATOR Principle In cyclone separator, the centrifugal force is used to separate solids from fluids. The separation depends not only on the particle size but also on density of particles. Hence depending on the fluid velocity, the cyclone separator can be used to separate all types of particles or to remove only coarse particles and allow fine particles to be carried through with the fluid. 12 106 BP304T-PHARMACEUTICAL ENGINEERING

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108. Construction It consists of a cylindrical vessel with a conical base. In the upper part of the vessel is fitted with a tangential inlet and a fluid outlet and at the base it is fitted with solid outlet. Working The suspension of a solid in gas (usually air) is introduced tangentially at a very high velocity, so that rotary movement takes place within the vessel. The fluid is removed from a central outlet at the top. The rotatory flow within the cyclone separator causes the particles to be acted on by centrifugal force. The solids are thrown out to the walls, thereafter it falls to the conical base and discharged out through solids outlet. Uses Cyclone separators are used to separate the suspension of a solid in a gas (air). It can be used with liquid suspensions of solids. 14 108 BP304T-PHARMACEUTICAL ENGINEERING

109. AIR SEPARATOR Principle It works on the same principle as that of cyclone separator. But in this case the air movement is obtained by means of rotating disc and blades. To improve the separation, the stationary blades are used. By controllin 1 g 5 these blades and the speed of rotation, it is possible to vary the size at which separation occurs. 109 BP304T-PHARMACEUTICAL ENGINEERING

110. Construction It consists of a cylindrical vessel with a conical base. In the upper part of the separator the vessel is fitted with feed inlet, and at the base there are two outlets, one for line particles and other for heavy particles. The rotating disc and rotating blades are attached to the central shaft, to produce air movement Working As shown in the Fig. 6-3, the sample powder is passed through the feed inlet, which falls on the rotating disc. The rotating blades are attached to the same shaft. These produce a current of air as shown by the arrows. The fine particles are picked up and are carried into space, where air velocity is sufficiently reduced. The fine particles are dropped and ultimately collected at an outlet meant for fine particles. The heavy particles which fall downward are removed at an outlet meant for heavy particles. Uses Air separator is often attached to the ball mill or hammer mill to separate and return oversized particles for further size reduction 16 110 BP304T-PHARMACEUTICAL ENGINEERING

111. Elutriation Method: The size separation of powder is based on the low density of fine particles and high density of the coarse particles. Elutriating tank is used to separate the coarse and fine particles of powder after levigation. The dry powder or paste made by levigation process is kept in an elutriating tank and mixed with a large quantity of water. The solid particles are uniformly distributed in the liquid by stirring and then it is allowed to settle down. Depending on the density of solid particles, it will either settle down or remain suspended i 1 n 7 v water. 111 BP304T-PHARMACEUTICAL ENGINEERING

112. The sample is withdrawn at different heights through the outlets . These are dried and thus the powder with various size fractions are collected Nowadays in elutriation process, the particles are suspended in a moving fluid, generally water or air. The apparatus consists of a vertical column with an inlet near the bottom for suspension, an outlet at the base for coarse particles and an overflow near the top for fluid and fine articles. One column will give single separation into two fractions. If more than one fraction is required a number of tubes of increasing area of cross section can be connected in series. The velocity of the fluid decreases in succeeding tubes as the area of cross section increases, thus giving a number of fractions. These fractions are separated and dried. 18 112 BP304T-PHARMACEUTICAL ENGINEERING

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114. Advantages of Elutriation Method The process is continuous. Depending on the number of fractions required, the same number of tubes of different area of cross section can be connected. The separation is quick as compare to other methods of separation. The apparatus is more compact than as that used in sedimentation methods. The main disadvantage of this method is that the suspension of solid particles has to be diluted which may not be desired in certain cases. 20 114 BP304T-PHARMACEUTICAL ENGINEERING

115. MULTIPLE CHOICE QUESTIONS The process in which heavier component in mixture settles down when water is added to it is called a. Sedimentation b. Filtration c. Condensation d. Evaporation 2. Metal used for construction of sieve is Stainless Steel Nylon Terylene Magnesium 115 BP304T <Pharmaceutical engineering>

116. 3. Sieve no.10 contain: A.  10 wiers per inch n each direction B.  10 meshes per inch in each direction C.  Both (a) and(b) D.  None of the above 4. Moderately fine powder must pass through sieve no: A.  221 B.  44 C.  4 D.  120 BP304T <Pharmaceutical engineering> 116

117. 5. The limit of sieve number for coarse powder is: A.  10/44 B.  22/60 C.  44 D.  85 6. Very fine powders must pass through the sieve no: A.  85 B.  100 C.  44 D.  120 117 BP304T <Pharmaceutical engineering>

118. 7 . Micromeritics deals wth the study of: A.   Powderss B.  Microspores C.  Metric system of measurement D.  Small particle 8. Which of the following is not type of flow meters a. Orifice meter b. Pitot tube c. Potentiometer d. Rotameter BP304T <PHARMACEUTICAL ENGINEERING> 118

119. 9. The point at which diameter of fluid stream get less than initial volume of diameter is called a. Vena contracta b. Critical point c. cutectic point& d. Freezing point 10. Which of the following is also known as variable head meter a. Orifice meter b. Rotameter c. Venturi meter d. Pitot tube%. BP304T <PHARMACEUTICAL ENGINEERING> 119

120. 11. As compared to Ball miil , tube mill a. Has higher length diameter ratio b. Has large ball size c. Produce coarse size particle d. All of the above 12. Ball Mill is used for a. Attrition b. Very fine grinding C. Coarse grinding d. Both a and c BP304T <PHARMACEUTICAL ENGINEERING> 120

121. 13. Which of the following is also called slant manometera . Inclined manometerb . Inverted Utube differential manometerc . Simple manometerd . U tube differential manometer 14. Which of the following law states that the energy required for the size reduction of unit mass is proportional to the new surface area produced. a. Rittinger's law b. Bond's Law c. Fourier's Law d. Kick's Law BP304T <PHARMACEUTICAL ENGINEERING> 121

122. 15. In End runner mill, Size reduction is done by a. Cutting b. Crushing and sharing c. Impact d. Heating 16. Size reduction is also known as a. Comminution b. Compaction c. Segregation d. Seperation BP304T <PHARMACEUTICAL ENGINEERING> 122

123. 17. In Ball Mill, maximum size reduction is obtained at a. Low speed b. Very high speed c. Critical speed d. High speed 18. The process in which the material is crushed between the rollers by application of pressure is called a. Compression b. Impact c. Attrition d. Cutting BP304T <PHARMACEUTICAL ENGINEERING> 123

124. 19. Which of the following are objectives of size reduction? a. Increase surface area b. Stability of suspension c. Increase absorptiond . All of the above 20. In Ball Mill, maximum size reduction is obtained at a. Low speed b. Very high speed c. Critical speed d. High speed BP304T <PHARMACEUTICAL ENGINEERING> 124

125. 21 125 BP304T-PHARMACEUTICAL ENGINEERING