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1. Industrial pharmacy 8/7/2022 1 Industrial pharmacy is a discipline which includes manufacturing, development, marketing and distribution of drug products including quality assurance of these activities The reasons for the increasing of large scale manufacturing Economic – As the scale of manufacturing batches increases so, proportionally, does the cost of production decreases Accuracy – The larger the quantities of materials involved so, proportionally, is the accuracy of measurements increased Greater scope – The increasing complexity of modern therapy has made it virtually impossible to prepare many medicaments on a small scale

2. The Fundamentals unit operations 8/7/2022 2 In a pharmaceutical industry a unit operation is a basic step in a process Eg. tablet processing: mixing, milling, drying and sifting It is convenient to break down the processes for the manufacture of pharmaceutical products into unit operations those unit operations are not fundamenta l All unit operations involve and are controlled, to a greater or lesser extent, by one or more of the following basic processes. Fluid flow Heat transfer Mass transfer

3. Fluid flow 8/7/2022 3 Fluids are a form of matter that cannot achieve equilibrium under an applied shear stress but deform continuously, or flow, as shear stress is applied. Certain aspects of all the unit operations employ the movement of a fluid through pipes or between or around particles, etc Mechanism of Fluid Flow When a fluid flows through a pipe , the character of the flow can vary according to the conditions

4. Reynolds’ experiment 8/7/2022 4 a long glass tube was connected to a reservoir providing a constant head of water, with the control valve at the outlet so that the rate of flow could be varied In the inlet of the tube a jet was inserted which allowed a colored liquid to be injected into the center of the tube for the visualization of the flow behavior

5. Cont… 8/7/2022 5 When the velocity is low, the thread of colored liquid remains undisturbed in the center of the water stream and moves steadily along the tube, with out mixing, this condition is known as streamline or laminar flow (a) At moderate velocities, a point is reached (the critical velocity) at which the thread begins to waver, although no mixing occurs. This is the phase of transitional flow. As the velocity is increased to high values eddies begin to occur in the flow, so that the colored liquid mixes with the bulk of the water immediately after leaving the jet. Since this is a state of complete turbulence, the condition is known as turbulent flow.

6. Cont… 8/7/2022 6 Reynolds found that flow conditions were affected by four factors Diameter of pipe Velocity of fluid Density of fluid Viscosity of fluid Re = ρ vd / μ where Re = Reynolds Number ρ = density of fluid (kg/m3) v = velocity of fluid (m/s) d = diameter of pipe (m) μ = viscosity of fluid (kg/m. s) Reynolds number is just a number and it has no dimensions

7. Distribution of Velocities Across the Tube 8/7/2022 7 When a fluid flows along a tube, not all parts are moving at the same velocity The fluid in the center travels at the highest velocity and that at the walls at the lowest In laminar flow; Fluid in the centre can move at highest velocity with frictional force causing a continual decrease in the velocity towards the walls

8. Boundary Lines 8/7/2022 8 whether flow in the tube is laminar or turbulent, the velocity reaches very low values near the walls ultimately, it becomes zero at the wall itself Reynolds Number is proportional to the velocity So similar decrease in the value of the local Re. This means that there will be a change from turbulence, through a transitional region to a sluggish streamline region and finally, to a stationary film on wall. that boundary layers can never be eliminated Increasing the velocity of the fluid over the surface will reduce the thickness of the layer

9. 1.2 Heat Transfer 8/7/2022 9 Heat is a form of energy. It can only be transferred from a region of higher temperature to a region of lower temperature Many pharmaceutical unit operations like distillation, drying, evaporation, sterilization etc involve the application of heat Heat is transferred by three mechanisms Conduction : is the transfer of heat through a static material by direct contact of particles of matter is greater in solids , where atoms are in constant contact is limited to solids and to fluids that are ‘bound’ in some way that prevents free movement

10. Cont… 8/7/2022 10 Convection : is the transfer of heat from one point to another within a fluid (gas, liquid) by the mixing of one portion of the fluid with another In convection, the heat flow results from mixing or turbulence, which can occur in fluids only Radiation : is the transfer of heat energy through empty space No medium is necessary for radiation to occur

11. Cont… 8/7/2022 11

12. Heat transfer by conduction 8/7/2022 12 Conduction is the most familiar and widely understood mechanism of heat transfer When heat is flowing under steady-state conditions, the quantity of heat transferred is given by :

13. 8/7/2022 13 k ,which is characteristic for any material, is known as the coefficient of thermal conductivity Thermal conductivities vary considerably, ranging from metals that have high values to gases that have the lowest values Material Thermal conductivity (J/ sm°c ) Copper 379 Aluminum 242 Steel 43 Glass 1 Water 0.6 Air 0.03

14. 1.3 Mass transfer 8/7/2022 14 involves the movement of material from one phase to another Eg . in drying a wet solid, the liquid is converted to vapor and carried away in that form when a drug is extracted with a solvent, soluble material passes from the solid phase into solution and is taken away in the liquid phase

15. Solid fluid mass transfer 8/7/2022 15 Consider a crystal of a soluble material immersed in a solvent in which it is dissolving transport of the molecules of the dissolving solid will take place in two stages First the molecules move through the boundary layer by molecular diffusion, with no mechanical mixing Once material has passed through the boundary layer, mass transfer takes place by bulk movement of the solution, known as eddy diffusion, the controlling factor in the rate of solution of the crystal will be the molecular diffusion through the boundary layer

16. Cont… 8/7/2022 16 Eddy diffusion will not be considered further since, in general, molecular diffusion is the controlling process Equation for mass transfer by molecular diffusion

17. Factors affecting Solid fluid mass transfer 8/7/2022 17 Agitation , which reduces the thickness of the boundary layers and disperses any local concentrations of solution, so increasing the concentration gradient. Elevated temperatures which increase the diffusion coefficient and decrease the viscosity of the liquid, so reducing boundary layer thickness. Size reduction of the solid , which increases the area over which diffusion can occur.

18. Unit operations 8/7/2022 18 Unit operations :- are different processes and equipments required in the manufacturing of pharmaceuticals Size reduction Mixing Drying Filtration C rystallization

19. Drying 8/7/2022 19 Removal of water or other liquid from a solution, suspension or solid –liquid mixture to form a dry solid involves heat transfer and mass transfer Drying and evaporation are distinguishable merely by the relative quantities of liquid removed from the solid Purpose of drying/Application of Drying In the preparation of granules Stabilizes moisture sensitive materials :-Aspirin & penicillin To aid in the preservation of animal and vegetable drugs by minimizing mold and bacterial growth .

20. Factors affecting drying 8/7/2022 20 The critical factor in drying operations is the vapor - carrying capacity of the air, nitrogen, or other gas stream passing over the drying material The vapor - carrying capacity determines both rate and extent of drying Heat sensitivity of the product Physical characteristics of the product Nature of solvent to be removed

21. Convective Driers for Wet Solid 8/7/2022 21 Tray Drier Air flows in the direction of the arrows over each shelf in turn The wet material is spread on shallow trays resting as the shelves The required latent heat of evaporation is transferred convectively from the air Slow heat transfer=> slow rate of drying

22. Dynamic Convective Driers 8/7/2022 22 Fluidized Bed Drier(FBD) There is an excellent contact between the warm drying air and the wet particle The material to be dried is contained in a vessel, the base of which is perforated enabling a fluid (air) to pass through the bed of the solid from the bottom

23. Advantages of Fluidized Bed Drying 8/7/2022 23 Efficient heat and mass transfer. This attributes to Short drying time (20-30 min) Good for thermolibile materials Drying occurs from the surface of the individual particles No migration of soluble API & Expients The temperature of the fluidizing bed is uniform throughout and can be controlled precisely Turbulence cause attrition – More spherical free flowing particles The container can be mobile, good for material handing (Loading and Unloading )

24. Disadvantages of FBD 8/7/2022 24 Turbulence – Excessive attrition Production of too much dust –> too fine –> flow problem – >segregation Generation of static electricity Mixture of air with organic materials (starch and lactose) can cause explosion The danger is increased if the fluidizing material contains volatile solvents such as isopropyl alcohol Therefore, adequate electrical earthing is essential

25. Conductive Drying of wet solids 8/7/2022 25 The wet solid is in thermal contact with a hot surface and heat transfer mainly occurs by conduction Vacuum Oven Consists of a jacketed Vessels sufficiently strong in construction to with stand vacuum and steam pressure in the jacket Operating pressure can be as low as 0.03-0.06 bar,H 2 O boils at25-35 c [[[ Commonly used in pharma R & D`s Advantages: For thermolibile products Minimum oxidation

26. Radiation drying of wet solid 8/7/2022 26 Microwave (MW) Radiation Microwave radiation in the Wave length of 10nm-1nm penetrates much better than IR More application in pharma than IR dries does Microwaves are produced by an electronic devices known as magnetron When MW falls on substances of suitable electronic structure (Polar molecules e.g. water), the electrons in molecules attempt to resonate in sympathy with the radiation and the resulting molecular friction which in turn causes generation of heat

27. Advantage of MW drying 8/7/2022 27 Rapid drying at fairly low Temp. Thermal efficiency is high most of the MW is absorbed by the liquid No heating of the air The bed is stationary avoiding the problem of dust generation Solute migration is reduced as there is uniform heating of the wet mass. Equipment is highly efficient and refined All product and operators safety have been incorporated CGMP compliant Drying end point detection is possible

28. Disadvantages of MW drying 8/7/2022 28 Smaller batches sizes are used as compared to FBD Safety issues. Care should be taken to shield operators from the MW radiation which can cause damage to the eyes and testes

29. Driers for Dilute solutions and suspensions 8/7/2022 29 Objective To spread the liquid to a large surface area for heat and mass transfer and to provide an efficient means of collecting the dry solid Two main types are used Spreading the liquid to a thin film on a drum Dispersing the liquid to a spray of small droplets

30. Drum driers 8/7/2022 30 consists of a drum 0.75-1.5m in diameter and 2-4m in length It is heated internally by steam The liquid is applied to the surface of the drum and spread to a film This is usually performed by deeping the drum in the feeding pan Drying rate is controlled by Manipulating the speed of the drum Manipulating Temp. The product is scraped from the surface of the drum by means of a knife

31. Advantages of the drum drier 8/7/2022 31 gives rapid drying =>rapid heat and mass transfer The equipment is compact less space than spray drier Heating time is short (a few sec) The drum can be enclosed in vacuum =>the drying Temp. can be reduced The product is obtained in flake form which is convenient for many purposes

32. Disadvantages 8/7/2022 32 Operation conditions are critical i.e. it is necessary to impose careful control on Feed rate Film thickness Speed of drum Drum Temperature Pharmaceutical applications Drying of starch products Ferrous salt Suspensions of Zn oxide

33. Spray Driers 8/7/2022 33 Provides a larger surface area for heat and mass transfer Works by atomizing the liquid to small droplets The liquid is sprayed into a stream of hot air Each droplet dries to an individual solid particles Mechanism of drying The air enters the chamber tangentially and rotates the drying droplets around the chamber to increase their residence time The air is heated by heat exchangers Dust carried over in the air is recovered by cyclone separator of filter Physical characteristics of spray dried products Uniform in appearance Hallow spheres due to blowing air in sphere particles

34. Cont… 8/7/2022 34

35. Advantages of the spray Drying process 8/7/2022 35 Rapid drying (fraction of sec) Evaporation is rapid =>the droplets do not attain high Temp. good for thermolibile products High bulk density=> rapid dissolution due to increased surface area Uniform and controlled particle size The product is free flowing as the particles are spherical in shape Low labor costs. No human handling

36. Disadvantages 8/7/2022 36 The equipment is very bulky Thermal efficiency is low as the air is still hot when it leaves the drier Pharmaceutical Application Gelatin Starch Some powdered antibiotics for reconstitution into syrup Particles in 1-7mm can be dried and used in DPI (dry powder inhalers) Can be operated with inert gases for 0 2 sensitive products .

37. Freeze drying ( lyophilization ) 8/7/2022 37 Many products of pharmaceutical lose their viability in the liquid state and readily deteriorate if dried in air at normal atmospheric pressures It works by freezing the material and then reducing the surrounding pressure and adding enough heat to allow the frozen water in the material to sublime directly from the solid phase to gas

38. Advantages 8/7/2022 38 1. Drying takes place at low Temp., so that enzymes action is inhibited and chemical decomposition, particularly hydrolysis, is minimized 2. The solution is frozen such that the final dry product occupy the same volume as the original solution 3. Fast solubility due to high porosity 4. The process takes place under high vacuum; there is little chance for oxidation

39. Disadvantage 8/7/2022 39 1. Very hygroscopic substance. The products should be dried in their final containers and sealed in situ 2. The process is very slow and uses complicated plants and not universal method . Uses For drying of Biological products Such as Antibiotics, blood products and vaccines, and enzyme preparations

40. Size Reduction 8/7/2022 40 is the mechanical process of reducing the particle size of a substance to smaller pieces, to coarse particles, or to powder Various terms have been used synonymously with size reduction depending on the product, the equipment, and the process Crushing , Grinding, Milling, Pulverization and Dispersion particle size affects a number of characteristics in the manufacturing process controlling the particle size helps assure that the milled material will be consistent and repeatable with respect to a lot of quality and processing variables

41. the most common reasons for reducing material sizes 8/7/2022 41 Create appropriate particle sizes for subsequent processing or end use Color - uniform particles assure batch-to-batch colo consistency /less chance for mottling/ Improve material blending and prevent segregation by making different sized products with similar particle size distributions Increase the material’s surface area to improve a material’s solubility Examples:- decrease particle size of griseofulvin decreased oral dosage regimen half. To facilitate drying of wet masses reduces the distance the moisture must travel to reach the outer surface

42. Factors affecting size reduction 8/7/2022 42 Hardness Hard materials are difficult to comminute Toughness It is often more important than hardness, so that a soft but tough material may present more problems in size reduction than a hard but brittle substance. Ex. - Rubber - Fibrous drugs Rubber are capable of absorbing large amount of energy through elastic and plastic deformation Such materials can be milled by cooling Stickiness It may cause difficulty in size reduction, since a material acts as a lubricant & lowers efficiency of the grinding surfaces. Example:- Grinding of gummy or resinous materials

43. Cont… 8/7/2022 43 Softening Temperature The heat during size reduction processes softens and melts materials with a low melting point. Ex. – Synthetic gums and resins - Heat-sensitive drugs may be degraded or even charred Moisture content An increase in moisture can decrease the rate of size reduction to a specified product size The presence of more than 5% water hinder comminution and often produces a sticky mass upon milling Only a small amount of energy put into a milling operation actually effect size reduction (2%)

44. Methods for size reduction 8/7/2022 44 There are four main methods of effecting size reduction Cutting :- the material is cut by means of a sharp blade or blades Compression :- the material is crushed by application of pressure Impact :- material is hit by an object moving at a high speed or it strikes a stationary surface and the material is broken down into small places Attrition :- the pressure is applied to the material as in the case of compression, but the surfaces are in motion relative to each other.

45. Cutting 8/7/2022 45 The cutter mill consists of a series of knives attached on a horizontal rotary which act against a series of stationary knives attached to the mill casing. Size reduction occurs by fracture of particles between the two sets of knives which have a clearance of a few millimeters Application To produce a coarse degree of size reduction of dried granulation prior to tableting To mill fibrous crude drugs such as roots or barks prior to extraction

46. Cont… 8/7/2022 46

47. Compression 8/7/2022 47 Size reduction range 10-100 μ m Direct-pressure milling occurs when a particle is crushed or pinched between two hardened surfaces Two rotating bars or one rotating bar and a stationary plate generally produce this milling action Used in small scale by using a mortar and pestle In large scale there are: End runner mill- a weighted pestle is turned by friction of material passing beneath it- a mortar rotates under the powder Edge runner mill - a pestle rotates against a bed of powder

48. Alternative technique/Roller Mill/ 8/7/2022 48 Compression mill which uses two cylindrical rollers mounted horizontally and rotated about their long axes In rollers, one of the rollers is rotating and the other one is rotated by friction. This are not like ointment mills where both rolls are driven at different speed and size reduction occurs by attrition The commonest method in the pharmaceutical industry USE - used for crushing, such as cracking the seeds of fixed oils to aid solvent penetration in extraction

49. Attrition milling (1-100 μ m) 8/7/2022 49 Is used for the Size reduction of solids in suspensions, pastes and ointments Roller Mill Two or more metal rolls are mounted horizontally with an adjustable gap which can be as small as 20 μ m The rollers rotate at different speeds so that the material is sheared as it pass though the gap The material is transformed from the slower to the faster roll The material (milled) is removed by scraper

50. Impact milling (1-10000 μ m) 8/7/2022 50 A hammer mill A hammer mill consists of a four or more hammers hinged on a central shaft which is enclosed in a rigid metal case During milling, the hammer swing out radially from the central shaft As size reduction continues the inertia of particles hitting the hammer reduces and sequentially fracture is less probable Hence, hammer mill tend to produce powders with narrow size distribution

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52. Cont… 8/7/2022 52

53. Cont … 8/7/2022 53 Example-2 Alternative Technique (Vibration Milling ) Uses a drum where 80% of the content is filled with porcelain or steel balls During milling, the whole body of the mill is vibrated and size reduction occurs by repeated impaction Comminuted particles fall through a screen at the base of the mill The efficiency of vibration milling is greater than that of the conventional ball mill

54. Combined impact and attrition Method 8/7/2022 54 Ball mill Both impact and attrition methods are used Consists of a hollow cylinder containing balls (30-50%) of its space The amount of material in a mill is considerable important Speed of ball mill has a considerable effect on grinding At low speed – balls will slide or roll over each other At high speed – balls will be thrown out centrifugally and no grinding occurs

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56. Advantages of ball mill 8/7/2022 56 It is capable of grinding a wide variety of materials It can produce very fine powders It is economical and simple to operate It can be used for batch or continuous operation It can be used in completely enclosed form, which makes it especially suitable for use with toxic materials Disadvantages Contamination may happen because of wearing of balls and partially from casing. Soft materials may stick on the side of the mill.

57. Fluid Energy Mill 8/7/2022 57 Utilizes particle impaction and attrition Consists of a hallow tube with a diameter of 20-200mm A fluid (air) is injected as a high pressure jet through nozzles at the bottom of the loop The high velocity of the air gives rise to zones of turbulence into which solid particles are fed The high kinetic energy of air causes the particles to impact with each other A particle size classifier is incorporated so that particles are retained in the tube until sufficiently milled

58. Advantages Fluid energy mill 8/7/2022 58 The particle size of the product is smaller than that produced by any other method of size reduction Is used for thermolabile substances because the cooling effect counteracts the heat generated by milling There is no abrasion of mill so virtually no contamination of the product For very sensitive materials it is possible to use inert gases Having a classifier as an integral part of the system permits close control of particle size and of particle size distribution Use :- used for obtaining very fine powders, e.g. sulphonamides , vitamins, antibiotics

59. SIZE SEPARATION 8/7/2022 59 In pharmaceutical industry, the control of particle size and size range has great importance Standards for sieves There are different standards of sieves for standardization of particles size of powders Number of sieves :- this is the number of meshes in a length of 25.4 mm (1 inch), in each direction, parallel to the wires thus a number 10 sieve has 10 meshes in 2.54cm in each direction Nominal size of aperture :- this is the distance between the wires, so that it represents the length of the side of the square aperture

60. Size separation by sieving 8/7/2022 60 There are several techniques for encouraging particles to separate into their appropriate size fractions efficiently Agitation methods A . Oscillation :- The sieve is mounted in a frame that oscillated back and forth B. Vibration :- the mesh is vibrated at high speed, often by means of an electrical device Brushing methods   A brush can be used to move the particles on the surface of the sieve and to keep the meshes clear.

61. Cont … 8/7/2022 61 Centrifugal methods This type of sieve used a vertical cylindrical sieve with a high speed rotor inside the cylinder, so the particles are thrown outwards by centrifugal force Wet sieving Wet sieving is more efficient than the equivalent dry process, particles being suspended readily and passing easily through the sieve with less blinding of the meshes.

62. Mixing 8/7/2022 62 is a process in which two or more components in a separate or roughly mixed condition are treated so that each particle lies as nearly as possible in contact with a particle of each of the other ingredients Purposes of pharmaceutical mixing To ensure even distribution of the API To ensure even appearance To ensure the release of the drug at the correct site and at the desired rate

63. Types of Mixtures 8/7/2022 63 There are three types of mixture based on their behavior:- Positive mixtures These mixtures are formed when two or more miscible liquids are mixed together by diffusion process. Irreversible mixing would take place. Negative mixtures Hence insoluble solids are mixed with the vehicle to form a suspension or two immiscible liquids are mixed to form emulsion. require energy for their formation The components of which will separate unless work is continually expanded on them.

64. Cont… 8/7/2022 64 Neutral Mixtures Here mixing of pastes, ointments takes place. When two powders are mixed, then it forms a neutral mixtures Components of the mixture have no tendency to mix spontaneously, nor do they segregate when mixed They are static in their behavior

65. Mechanisms of solid mixing 8/7/2022 65 Convective mixing Arises when there is the transfer of relatively large group of particles from one part of the powder bed to another as might occur when a mixture blade or paddle moves through the mix In order to achieve a random mix an extended mixing time is required Shear mixings When a layer of material moves / flow over another layer

66. Cont.. 8/7/2022 66 Diffusion mixing When the powder bed is forced to move or flow This is because the powder particles will become less tightly packed and there is an increase in the voids space between them Under this circumstance, there is a potential for the particles to fall under gravity through the void created results in low rate of mixing N.B all three mixing mechanisms are likely to occur in a certain mixing operation

67. Mechanisms of Mixing for Liquids 8/7/2022 67 Bulk transport involves the movement of a relatively large amount of materials from one position in the mix to another It tends to produce a large degree of mixing fairly quickly Turbulent mixing Arises from the haphazard movement of molecules when forced to move in a turbulent manner Molecular diffusion Occurs with miscible fluid whenever a concentration gradient exists and will eventually produce a well mixed product

68. Powder Segregation / demixing / 8/7/2022 68 Segregation is the opposite effect to mixing i.e. components tend to separate out is very important in pharmaceutical preparations as it causes a non random mixing Effects of segregation Increased content variation Un acceptable variation in weight Processing difficulties Non uniform drug release rate

69. Causes of powder segregation 8/7/2022 69 Particle size effect It is the main cause of segregation Percolation segregation Smaller particles tend to fall through the void between larger ones and moves to the bottom of the mass. Example - during vibration, Stirring or poring b. Trajectory segregation During mixing larger particles will tend to have greater kinetic energy imparted to them and therefore will tend to move greater distance than smaller particles before come to rest

70. 8/7/2022 70 C. Elutriation segregation/Dusting out / When a material is discharged from a container, very small particles dust in a mix may tend to be blown upward by turbulent air current as the mass tumbles and remains suspended in the air Particle –density effect If component are of different density, the more dense materials will have a tendency to move downward even if the particles size are similar Particle shape Spherical particles exhibit the greatest flow ability and are therefore more easily mixed, but they also segregate more easily than non spherical particles

71. Approach to Rectify Segregation 8/7/2022 71 Selection of particle size fractions E.g. sieving to remove fins or lumps to achieve drug and excipients within narrow particles size distribution range Milling of components followed by sieving To reduce particle size range Controlled crystallization Selection of excipients which have densities similar to the API Avoid vibration /proper material handling/ Use of filling machine hopers designed so that powder residence time is minimized

72. Powder mixing equipment 8/7/2022 72 Tumbling mixer equipments Used for mixing /blending of granules of free flowing powders There are many designs Examples :Double cone mixers, Twin shells ,Cube mixers , y- cone mixers, Drum mixers Too high mixer speed Will cause the material to be held on the wall by the centrifugal force Too low mixer speed Will generate insufficient bed expansion and little shear mixing

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74. 8/7/2022 74 High speed mixer granulator( Rapid mixer granulators)(RMG) It both mixes and granulates Fluidized Bed mixers Used for mixing of powders prior to granulation Agitator mixers Eg -ribbon mixers

75. Mixing of Miscible Liquids and Suspensions 8/7/2022 75 Propeller mixer It has angled blade which cause the fluid to circulate in both axial and radial directions Turbine Mixer Used for more viscous fluids The impeller has four flat blades surrounded by perforated inner and outer diffuser rings

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77. Mixing of Semi solids 8/7/2022 77 The problem with semi solids is that they are not free flowing For this reason, mixers with rotating elements and narrow clearance between themselves and mixing vessels wall they must produce a high degree of shear mixing Sigma blade mixer /- mixer/

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79. Clarification (Filtration) 8/7/2022 79 Filtration is process that involves the removal or separation of a solid from a fluid or a fluid from another fluid The preparation of pharmaceutical dosage forms frequently requires the separation of particles from a fluid Objectives Sparkling liquid that is free of Crystalline precipitates or amorphous Colloidal hazes Insoluble liquid drops Removal of microbes or sterilization

80. Terminologies in Filtration 8/7/2022 80 Filters : - the porous (permeable) material that separates particles from the liquid passes through it Residue : - solids retained in the filter Effluent filtrate :- the classified liquid Cake filtration :- The solid forms a cake on the medium and if the recovery of this cake is required the process is called cake filtration Clarification : - When the solid to be filleted is not exceeding 1.0% and the filtrate is the primary product Ultrafiltration is used to separate colloidal particles and macromolecules by the use of a membrane Hydraulic pressure is used to force the solvent through the membrane, whereas the microporous membrane prevents the passage of large solute molecules

81. Principles of Filtration 8/7/2022 81 It is more of an art than a science The flow of liquid through a filter follows the basic rules that govern flow of any liquid through a medium offering resistance The rate of flow may be expressed as  Rate = driving force Resistance The rate is expressed as volume per unit time & the driving force as a pressure differential Rate of filtration :- ( dv ) (area of filter) x (pressure difference) ( dt ) (Viscosity) x (resistance of cake & filter)

82. Factors Affecting Filtration rate 8/7/2022 82 The area available for filtration (A) The pressure difference across the filter bed (filler medium and any cake formed) The viscosity of the fluid passing through the filter i.e. the filtrate( μ pas) increase viscosity =>greater resistance for movement The thickness of the filter medium and any deposited cake (L) Increased Cake = >decreased rate of filtration

83. Mechanisms of Filtration 8/7/2022 83 Straining (sieving) the pores are smaller than the particles to be filtered, and this results the particles to be retained on the filter medium. Example – Removal of bacteria and fibers from parental preparation Impingement -A liquid following pattern is disturbed eg . Used mainly for removal of materials from gases Entanglement If the filter medium consists of a cloth with a nap or is a porous , then particles become entangled in the mass of fibers Attractive forces Particles may collect on a filter medium as a result of attractive forces

84. Filtration Equipment 8/7/2022 84 Equipment selection Equipment should Allow a fast filtration rate Minimize production cost Cheap to buy and to run Be easily cleanable Be resistant to corrosion Be capable of filtering large volumes

85. Industrial Filtration Equipments 8/7/2022 85 Gravity Filter Filter that relay solely on gravity generate low operating pressure They are very simple and cheap and used in laboratories Are common in water treatment Ex - Sand filter Vacuum Filters The rotary Vacuum Filter is continuous in operation and has a system for removing the cake up to 2m in diameter and 3.5m in length with a filtration area of 20m 2 Used for continuous filtration of slurry containing 15-30% solids For collection of starch

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87. Advantages 8/7/2022 87 1. It is automatic and continuous in operation 2. It has a large capacity 3. Varied speed of rotation enables the cake thickness to be controlled Disadvantage 1. It is complex and expensive 2. Ancillary equipments like vacuum pump Vacuum receivers Slurry pumps are required 3. Less satisfactory for solids that forms impermeable cake

88. Pressure filters 8/7/2022 88 The product is fed to the filter at a high pressure Most commonly used for processing of pharmaceuticals I. The Meta filter The filter operates by pumping in the slurry under pressure Advantages High strength and no fear of bursting No filter medium (stainless steel). This makes it economical Application The small surface area restricts the amount of solid that can be collected. Thus, it is used exclusively for liquid with low level of contaminant ideal for filtration of viscous liquids

89. Cartridge filter 8/7/2022 89 Commonly used in the preparation of pharmaceutical products It poses a very large filtration surface area in a small unit and is easy and cheap to operate The cartridge is then fitted in a metal supporting cylinder and the product is pumped under pressure into one end of the cylinder

90. Air Filtration (High Efficiency Particulate Air (HEPA) filter) 8/7/2022 90 HEPA is a type of highly efficient filtration media that removes microscopic particles from air which passes through the filter The most efficient HEPA filter removes 99.7% of particles with a size of 0.3 η that enter the filter. Such particles include tobacco smoke, household dust, and pollen. ULPA filters, or "Ultra-HEPA" filters, are designed to trap 99.999% Usually Microban is used in HEPA filters which is used to treat the HEPA filter

91. 8/7/2022 91 In most industries HEPA filters work along with Dehumidifiers or humidity controllers and also along with steam line and chillers which controls the temperature in such cases the system is termed as Heating, Ventilation and Air conditioning system (HVAC system)

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93. Crystallization 8/7/2022 93 Crystallization refers to the formation of solid crystals from a homogeneous solution It is essentially a solid-liquid separation technique The processes by which a crystal forms are called nucleation and growth. Nucleation is the formation of a small mass on to which a crystal can grow. Growth is the addition of more solute molecules to the nucleation site In order for crystallization to take place a solution must be "supersaturated“ Supersaturation refers to a state in which the solvent contains more dissolved solute

94. Cont… 8/7/2022 94 Primary nucleation is the first step in crystallization. Simply defined, it's the growth of a new crystal The second chief mechanism in crystallization is called secondary nucleation requires "seeds" or existing crystals to achieve crystal growth The four most common methods of reaching supersaturation in industrial processes are: Cooling (with some exceptions) Ce 2 (SO 4 ) 3 Solvent Evaporation Drowning :addition of a nonsolvent to the solution which decreases the solubility of the solid Chemical Reaction: alter the dissolved solid to decrease its solubility in the solvent

95. Figure 3: Solubility's of Several Solids 8/7/2022 95

96. Equipment Used in Crystallization 8/7/2022 96 Tank Crystallizers the oldest and most basic method of crystallization saturated solutions are allowed to cool in open tanks After crystallization, the mother liquor is drained and the crystals are collected The crystallization is essentially just "allowed to happen“ Heat transfer coils and agitation can be used high operating costs

97. Forced Circulating Liquid Evaporator-Crystallizer 8/7/2022 97 T hese crystallizers combine crystallization and evaporation The circulating liquid is forced through the tube side of a steam heater The heated liquid flows into the vapor space of the crystallization vessel flash evaporation occurs, reducing the amount of solvent in the solution The supersaturated liquor flows down through a tube, then up through a fluidized area of crystals and liquor where crystallization takes place via secondary nucleation. Larger product crystals are withdrawn while the liquor is recycled, mixed with the feed, and reheated.