Filtration Celeste. todaro 1.0 INTRODUCTION The theoretical concepts underlying filtration can be applied towards practical solutions in the field. Comprehension of the basic principles is necessary to select the proper equipment for an application Theory alone, however, can never be the basis for selection of a filter Filtration belongs to the physical sciences, and thus conclusions must be based on experimental assay. It is, however, helpful in understanding why a slurry is more suitable for one design of filtration equipment than another Methods of optimization in the field can also be predicted by having a background in the theory Slurries vary significantly in filtration characteristics. Even batch to batch variation in product particle size distribution and slurry concentration will greatly influence filterability and capacity of a given filter. It is therefore, essential to evaluate a slurry in laboratory tests at a vendors facility or at one's plant with rental equipment to prove the application There three(3)types of pharmaceutical filtrations: depth, cake, and membrane. Cake and depth are coarse filtrations, and membrane is a fine final filtration. Membrane filtration and cross-flow filtration are discussed Ch. 7
Filtration Celeste L. Todaro 1.0 INTRODUCTION The theoretical concepts underlying filtration can be applied towards practical solutions in the field. Comprehension of the basic principles is necessary to select the proper equipment for an application. Theory alone, however, can never be the basis for selection of a filter. Filtration belongs to the physical sciences, and thus conclusions must be based on experimental assay. It is, however, helpful in understanding why a slurry is more suitable for one design of filtration equipment than another. Methods of optimization in the field can also be predicted by having a background in the theory. Slurries vary significantly in filtration characteristics. Even batch to batch variation in product particle size distribution and slurry concentration will greatly influence filterability and capacity of a given filter. It is, therefore, essential to evaluate a slurry in laboratory tests at a vendor’s facility or at one’s plant with rental equipment to prove the application. There are three (3) types ofpharmaceutical filtrations: depth, cake, and membrane. Cake and depth are coarse filtrations, and membrane is a fine, final filtration. Membrane filtration and cross-flow filtration are discussed in Ch. 7. 242
Filtration 243 1.1 Depth Filtration Examples of depth filtration are sand and cartridge filtration. Solids are trapped in the interstices of the medium. As solids accumulate, flow approaches zero and the pressure drop across the bed increases. The bed must then be regenerated or the cartridge changed For this reason, this method is not viable for high solids concentration streams as it becomes cost prohibi- tive. Cartridge filtration is often used as a secondary filtration in conjunction with a primary, such as the more widely used cake filtration 2.0 CAKE FILTRATION Rates of filtration are dependent upon the driving force of the piece of equipment chosen and the resistance of the cake that is continually forming Liquid flowing through a cake passes through channels formed by particles of irregular shapes 3.0 THEORY 3.1 Flow Theory Flow rate through a cake is described by Poiseuilles equation Ade V= volume of filtrate A= filter area surface 0= time P= pressure across filter medium a= average specific cake resistance weight of cake r resistance of the filter medium
Filtration 243 1.1 Depth Filtration Examples of depth filtration are sand and cartridge filtration. Solids are trapped in the interstices of the medium. As solids accumulate, flow approaches zero and the pressure drop across the bed increases. The bed must then be regenerated or the cartridge changed. For this reason, this method is not viable for high solids concentration streams as it becomes cost prohibitive. Cartridge filtration is oflenused as a secondary filtration in conjunction with a primary, such as the more widely used cake filtration. 2.0 CAKE FILTRATION Rates of filtration are dependent upon the driving force of the piece of equipment chosen and the resistance of the cake that is continually forming. Liquid flowing through a cake passes through channels formed by particles of irregular shapes. 3.0 THEORY 3.1 Flow Theory Flow rate through a cake is described by Poiseuilles’ equation: dV P V = volume of filtrate A = filter area surface 8 = time P = pressure across filter medium a = average specific cake resistance w = weight ofcake r = resistance of the filter medium u = viscosity
244 Fermentation and Biochemical engineering handbook In other words Flow Rate Fo Unit Area Viscosity([Cake Resistance Filter MediumResistance 3.2 Cake Compressibility The specific cake resistance is a function of the compressibility of the where constant As s goes to 0 for incompressible materials with definite rigid cryst line structures. a becomes a constant For the majority of products, resistance of the filter medium negligible in comparison to resistance of the cake, thus eq (1)becomes dy Eq1(3) de ua(W/A) Incompressible cakes have flow rates that are dependent upon the pressure or driving force on the cake. In comparison, compressible cakes, i.e where s approaches 1.0, exhibit filtration rates that are independent of pressure as shown beloy de ua(WlA) The above equations are detailed in Perry s Chemical Engineer's a00 [ Compressible cakes are composed of amorphous particles that are easily deformed with poor filtration characteristics. There are no defined channels to facilitate liquid flow as in incompressible cakes Fermentation mashes are typical applications of compressible materi- als, usually having poor filterability in contrast to purified end products that are postcrystallization. These products precipitate from solutions as defined crystals
244 Fermentation and Biochemical Engineering Handbook In other words, Flow Rate - Force Unit Area - Viscosity[ CakeResistance + FilterMediumResistance] 3.2 Cake Compressibility The specific cake resistance is a function of the compressibility of the cake. where a’ = constant As s goes to 0 for incompressible materials with definite rigid crystalFor the majority of products, resistance of the filter medium is line structures, a’ becomes a constant. negligible in comparison to resistance of the cake, thus Eq. (1) becomes AP - dV de ,ua(WlA) -_ Incompressible cakes have flow rates that are dependent upon the pressure ordrivingforce onthecake. Incomparison, compressiblecakes, i.e., where s approaches 1.0, exhibit filtration rates that are independent of pressure as shown below. The above equations are detailed in Perry’s Chemical Engineer ’s Handbook.[’] Compressible cakes are composed of amorphous particles that are easily deformed with poor filtration characteristics. There are no defined channels to facilitate liquid flow as in incompressible cakes. Fermentation mashes are typical applications of compressible materials, usually having poor filterability in contrast to purified end products that are postcrystallization. These products precipitate from solutions as defined crystals
ation 245 4.0 PARTICLE SIZE DISTRIBUTION Modification and optimization of a slurry, whether amorphous or crystalline, in the laboratory can yield significant improvements in filtration rates. By modeling the process in the laboratory, one can model what is occurring in the plant It is evident that attention paid in the laboratory to the factors affecting particle size distribution will save on capital investments made for separation equipment and downstream process equipment. Specific cake resistance( can be determined in the laboratory over the life of a batch, to evaluate if time in the vessel and surrounding piping system is degrading the product particle size to the point it impedes filtration, washing and subsequent drying Factors such as agitator design, agitation rates, pumps, slurry lines and other equipment, which can unnecessarily reduce the particle size, should be taken into consideration. Increasing the particle size in the slurry, and narrowing the particle size distribution will result in increased flow rates Large variations in particle size will increase the compressibility of a cake per unit volume. Since small particles have greater total cumulative surface areas, they will have higher moisture contents. For example, flour and water, when filtered with the same pressure or driving force as sand and water, will have a higher residual moisture level, thereby increasing the downstream dryer size. In the plant, the type of pump and piping system used to feed the filter are often of great importance, as time spent on crystallization and improving crystal size and particle size distributions can be quickly undone through particle damage. Recirculation loops and pumps for slurry uniformity may not always be necessary A review of the most commonly used process pumps are discussed Diaphragm pumps. These offer very gentle handling of slurries and are inexpensive and mobile. However, the pulsating flow can cause feeding and distribution prob- lems in some types offiltration systems, e.g., conventional basket centrifuges. They can also interfere with proces instrumentation e.g., flowmeters and loadcells Centrifugal pumps. Probably the most common source of particle attrition problems is the centrifugal pump. the high shear forces inherent to these pumps, particularly in the eye of the impeller, make some crystal damage
Filtration 245 4.0 PARTICLE SIZE DISTRIBUTION Modification and optimization of a slurry, whether amorphous or crystalline, in the laboratory can yield significant improvements in filtration rates. By modeling the process in the laboratory, one can model what is occurring in the plant. It is evident that attention paid in the laboratory to the factors affecting particle size distribution will save on capital investments made for separation equipment and downstream process equipment. Specific cake resistance (a) can be determined in the laboratory over the life of a batch, to evaluate if time in the vessel and surrounding piping system is degrading the product’s particle size tothe point it impedes filtration, washing and subsequent drying. Factors such as agitator design, agitation rates, pumps, slurry lines and other equipment, which can unnecessarily reduce the particle size, should be taken into consideration. Increasing the particle size in the slurry, and narrowing the particle size distribution will result in increased flow rates. Large variations in particle size will increase the compressibility of a cake per unit volume. Since small particles have greater total cumulative surface areas, they will have higher moisture contents. For example, flour and water, when filtered with the same pressure or driving force as sand and water, will have a higher residual moisture level, thereby increasing the downstream dryer size. In the plant, the type of pump and piping system used to feed the filter are often of great importance, as time spent on crystallization and improving crystal size and particle size distributions can be quickly undone through particle damage. Recirculation loops and pumps for slurry uniformity may not always be necessary. A review of the most commonly used process pumps are discussed below: Diaphragm pumps. These offer very gentle handling of slurries and are inexpensive and mobile. However, the pulsating flow can cause feeding and distribution problems in some types offiltration systems, e.g., conventional basket centrifuges. They can also interfere with process instrumentation e.g., flowmeters and loadcells. CentriJGgal pumps. Probably the most common source ofparticle attrition problems is the centrifugal pump. The high shear forces inherent to these pumps, particularly in the eye of the impeller, make some crystal damage
246 Fermentation and Biochemical Engineering Handbook inevitable in all but the toughest crystals. This damage is exacerbated on recirculation loops, which involve mul tiple passes through the pump. Recessed impellers will reduce this damage, but will often still degrade particles to the point where filtration becomes very difficult Positive displacement pumps. The minimal shear opera- tion of progressing cavity or lobe pumps make them ideal for slurries. The non-pulsating flow is beneficial in most processes, but they are significantly more expensive and less portable than diaphragm pumps Additionally, a significant amount of attrition can be caused by the particles"rubbing against each other. Therefore, long lengths of pipe, 900 elbows, throttling valves, control valves, and restrictions of any kind, should be avoided where possible. However, the type of pump employed is usually more significant Ifthe feed vessel can be mounted directly above the filter(to reduce the possibility of blockages), then gravity feeding with some pressure in the vessel is normally the best and least expensive arrangement. minimal shear agitators should be used at speeds sufficient to enhance the solids in the slurry and provide uniformity. Unnecessarily high speeds here can degrade the The"harder" the crystal, the more brittle and easier to break. Particle ape will also play a part, i.e spherical crystals dont break easily, needles do etc In general, this will lessen the problem of particle size deterioration and the fewer lines and shorter runs will reduce luggage 5.0 OPTIMAL CAKE THICKNESS As the cake thickness of a product varies, filtration rates and capacity will also change. Equation 4 shows that rates increase as the cake(W/a)mass decreases; thus, thin cakes yield higher filtration rates. This is particularly the case with amorphous materials or materials with high specific cake resistance. As a increases, maximizing dv/de requires W/a to decrease In continuous operations this can be done easily. In batch operations however, often filtration equipment cannot efficiently operate with extremely thin cakes. The long discharge times required to remove residual product in preparation for the next cycle, etc., make operation at a products optimal
246 Fermentation and Biochemical Engineering Handbook inevitable in all but the toughest crystals. This damage is exacerbated on recirculation loops, which involve multiple passes through the pump. Recessed impellers will reduce this damage, but will often still degrade particles to the point where filtration becomes very difficult. Positive displacement pumps. The minimal shear operation of progressing cavity or lobe pumps make them ideal for slurries. The non-pulsating flow is beneficial in most processes, but they are significantly more expensive and less portable than diaphragm pumps. Additionally, a significant amount of attrition can be caused by the particles “rubbing” against each other. Therefore, long lengths of pipe, 90° elbows, throttling valves, control valves, and restrictions of any kind, should be avoided where possible. However, the type of pump employed is usually more significant. If the feed vessel can be mounted directly above the filter (to reduce the possibility of blockages), then gravity feeding with some pressure in the vessel is normally the best and least expensive arrangement. Minimal shear agitators should be used at speeds sufficient to enhance the solids in the slurry and provide uniformity. Unnecessarily high speeds here can degrade the particles. The “harder” the crystal, the more brittle and easier to break. Particle shape will also play a part, Le., spherical crystals don’t break easily, needles do, etc. In general, this will lessen the problem of particle size deterioration and the fewer lines and shorter runs will reduce pluggage. 5.0 OPTIMAL CAKE THICKNESS As the cake thickness of a product varies, filtration rates and capacity will also change. Equation 4 shows that rates increase as the cake ( W/A) mass decreases; thus, thin cakes yield higher filtration rates. This is particularly the case with amorphous materials or materials with high specific cake resistance. As a: ‘ increases, maximizing dV/de requires W/A to decrease. In continuous operations this can be done easily. In batch operations however, often filtration equipment cannot efficiently operate with extremely thin cakes. The long discharge times required to remove residual product in preparation for the next cycle, etc., make operation at a product’s optimal