Pharmacy and Biotechnology Lecture Notes PDF

Pharmacy and Biotechnology Department of Pharmaceutical Technology Pharmaceutical Technology II [PHTCt 934] LECTURE 2: “MIXING - II” COURSE INSTRUCTORS: PROF. SAMAR MANSOUR DR. RADWA ABD EL MONIEM Dr. Radwa Abd El Moniem...

Pharmacy and Biotechnology Department of Pharmaceutical Technology Pharmaceutical Technology II [PHTCt 934] LECTURE 2: “MIXING - II” COURSE INSTRUCTORS: PROF. SAMAR MANSOUR DR. RADWA ABD EL MONIEM Dr. Radwa Abd El Moniem – Pharmaceutical Technology II [PHTCt 934) – Winter 2024 1 Lecture ILOs 2 At the end of this lecture, students will be able to: Recall different types of mixtures Enumerate different mixers used in solid mixing Enumerate different mixers used in liquid-liquid mixing Explain the design and operation of each mixer Differentiate between batch and continuous mixers Differentiate between different mechanisms of mixtures Lecture Outline 3 1. Recall types of mixing 2. Batch mixers: 1. High Shear Mixers 2. Air mixers 3. Continuous mixers: 1. Tumbling mixers 2. Stationary shell + rotatory mixing blade 3. Air mixers 4. Liquid- Liquid mixing 1. Mechanism of mixing 2. Types of mixers 1. Mechanical Agitation 2. Jet mixing 3. In line mixers 4. Homogenizers Dr. Radwa Abd El Moniem – Pharmaceutical Technology II [PHTCt 934) – Winter 2024  Mixing in Pharmaceutical Manufacturing Recall Types of mixing 4 Solid-solid mixing Liquid-liquid Solid-liquid mixing mixing Tablets Capsules Emulsion Solutions Suspension Solutions creams Sachets DPI Semisolid mixing Ointments Pastes Dr. Radwa Abd El Moniem – Pharmaceutical Technology II [PHTCt 934) – Winter 2024  Mixing in Pharmaceutical Manufacturing Solid – Solid Mixing 5 Types of Mixers Cheaper incase of small investments Drugs that require close system e.g. drugs that can be oxidized upon Batch exposure to environmental conditions Potent/ expensive drugs Types of Mixers Mainly in large investments Less time consuming, less workers Continuous 1.Tumbling mixers 2.Stationary shell + rotatory mixing blade 3.Fluid bed mixer Dr. Radwa Abd El Moniem – Pharmaceutical Technology II [PHTCt 934) – Winter 2024  Mixing in Pharmaceutical Manufacturing Solid – Solid Mixing 6 Types of Mixers – Batch Mixers Stationary shell + Tumbling Tumbling mixers + High Shear mixers rotatory mixing Air mixers mixers agitators (granulators) blade Drum Ribbon mixer (Stationary shell (Stationary shell V-shaped Cube Sigma blade with rotating using moving air Double cone Y-cone (V- mixer mixing blade as agitator) shaped) Planetary mixers and high – speed a. Fluid bed Double cone Conical screw agitator blade) granulator Slanted Solid- solid mixing mixers Barrel mixer b. Fluid bed drier double cone Solid- liquid mixing Bowl mixer Solid- solid mixing Solid- liquid mixing Granulators Solid – solid mixing Semisolid mixing Solid- solid mixing (except ribbon) Solid- liquid mixing Dr. Radwa Abd El Moniem – Pharmaceutical Technology II [PHTCt 934) – Winter 2024  Mixing in Pharmaceutical Manufacturing Solid – Solid Mixing 7 Batch Mixers – Stationary shell + rotatory mixing blade Ribbon mixer Sigma blade mixer Planetary mixer Conical screw mixer Increasing mixing efficiency  They are mechanically different from the tumbling shell-type blenders where the mixing forces are transferred to the powder bed by moving blades in a fixed shell.  The blades have different configurations for each specific designs and move the solid - solid or liquid – solid mixtures by the force exerted through a motor driven drive shaft. Dr. Radwa Abd El Moniem – Pharmaceutical Technology II [PHTCt 934) – Winter 2024  Mixing in Pharmaceutical Manufacturing Solid – Solid Mixing & Solid – liquid Mixing 8 Batch Mixers – Stationary shell + rotatory mixing blade Lid to avoid dusting of powder Mechanism of mixing? Powder inlet Is the ribbon mixer: and/or evaporation of liquids 1.Suitable for solid-liquid mixing? Packing 2.Easy to clean? Mixer shell 3.Suffer packing problems? glands 4.Suitable for mixing of friable granules? Ribbon blade Function of each part ? Powder Discharge  Ribbon Blender / Mixer: The most effective design of ribbon layout is the double spiral in which the outer ribbon moves the product in one direction and the inner ribbon moves it in the opposite direction. Dr. Radwa Abd El Moniem – Pharmaceutical Technology II [PHTCt 934) – Winter 2024  Mixing in Pharmaceutical Manufacturing Solid – Solid Mixing & Solid – liquid Mixing 9 Batch Mixers – Stationary shell + rotatory mixing blade Function of each part ? Dead zones Advantages Disadvantages Low Head space Possible attrition of large more friable particles or granules in a mixture Why? Cleaning may be a problem. Why? Potential packing problems. Why? Unmixed material are trapped in discharge spout. (Dead zones) ? Dr. Radwa Abd El Moniem – Pharmaceutical Technology II [PHTCt 934) – Winter 2024  Mixing in Pharmaceutical Manufacturing Solid – Solid Mixing & Solid – liquid Mixing 10 Batch Mixers – Stationary shell + rotatory mixing blade  Sigma blade mixer: Two sigma shaped blades are fitted horizontally in a W-shaped bowl.  Mixer is loaded from top and unloaded by tilting the entire bowl. This solves the problem of unmixed materials getting entrapped in the discharge spout.  The blades move at different speeds , which allows movement of powder from sides to centers.  The material moves top to downwards and gets sheared between the blades and the wall of the tough resulting cascading action.  Perforated blades can be used to break lumps and aggregates which creates high shear forces.  Blade (Sigma shape) and shell (double trough) design reduces dead zones in comparison to ribbon mixers. Making it more suitable for semi- Dead zones eliminated solid mixers than ribbon mixers Dr. Radwa Abd El Moniem – Pharmaceutical Technology II [PHTCt 934) – Winter 2024  Mixing in Pharmaceutical Manufacturing Solid – Solid Mixing & Solid – liquid Mixing 11 Batch Mixers – Stationary shell + rotatory mixing blade Sigma blade mixer:  Used in: 1. Solid-solid mixing 2. Solid-liquid mixing (wet granulation) 3. Kneading in baking industry 4. Semi-solid mixing e.g.: dispersion of solid APIs in ointments Is the sigma blade mixer: 1. Easy to clean? and pastes however further processing is required to break 2. Suffer packing problems? 3. Suitable for mixing of friable down powder agglomerates granules? Dr. Radwa Abd El Moniem – Pharmaceutical Technology II [PHTCt 934) – Winter 2024  Mixing in Pharmaceutical Manufacturing Solid – Solid Mixing & Solid – liquid Mixing 12 Batch Mixers – Stationary shell + rotatory mixing blade Raw material feed Lid to avoid dusting of powder and/or evaporation of liquids single or double blades that could be equipped with scrapers to eliminate dead zone Mixer shell  Planetary mixer has a mixer shell serving as mixing bowl which is removed from the mixer by either lowering it beneath the blade, or raising the blade above the bowl or both as in the case of larger size planetary mixers.  To eliminate dead zones, The blade shaft rotates around the periphery of the shell eliminating dead zones  The only disadvantage with planetary mixer is the limited size batch Dr. Radwa Abd El Moniem – Pharmaceutical Technology II [PHTCt 934) – Winter 2024  Mixing in Pharmaceutical Manufacturing Solid – Solid Mixing & Solid – liquid Mixing 13 Batch Mixers – Stationary shell + rotatory mixing blade Planetary mixer:  Used in : Mixing blade 1. Solid-solid mixing (less likely on its own, as a preliminary step in Mixing Shell granulation for example) 2. Solid-liquid mixing (wet granulation) 3. Kneading in baking industry Is the planetary mixer: 4. Semi-solid mixing e.g.: dispersion of solid APIs in ointments and 1.Suitable for solid-liquid mixing? 2.Easy to clean? pastes however further processing is required to break down 3.Suitable for mixing of friable granules? powder agglomerates. 4.Suffer packing problems? Dr. Radwa Abd El Moniem – Pharmaceutical Technology II [PHTCt 934) – Winter 2024  Mixing in Pharmaceutical Manufacturing Solid – Solid Mixing 14 Batch Mixers – Stationary shell + rotatory mixing blade Would the conical screw mixer have the same efficiency if it was mounted horizontally? Why? single or double screws. Discharge  The conical screw mixer (Nautamixer): consists of a conical vessel fitted, a rotating screw which is fastened to the end of a rotating arm at the upper end. The screw shaft rotates around the periphery of the cone and around itself, eliminating dead zones. Efficient mixing occurs via repetitive cycles of the aforementioned steps; lifting, dispersing, gravitational sedimentation.  1. The screw agitator, turning on its axis, produces a lifting action as it spirals the materials in an upward flow. 2. At the same time, orbiting the tank, the screw removes material away from the wall and deflects it into the center of the tank. 3. Material lifted by the screw gravitates downward, thoroughly intermixing with material being spiraled upwards. Dr. Radwa Abd El Moniem – Pharmaceutical Technology II [PHTCt 934) – Winter 2024  Mixing in Pharmaceutical Manufacturing Solid – Solid Mixing & Solid – liquid Mixing 15 Batch Mixers – Stationary shell + rotatory mixing blade  The conical screw mixer (Nautamixer):  It could be equipped with a spraying nozzle for solid-liquid mixing.  Used in: 1. Solid-solid mixing 2. With liquid injection systems could be used for solid-liquid mixing ( wet granulation) Liquid injection system 3. Semi-solid mixing Is the conical screw mixer: 1.Easy to clean? 2.Suitable for mixing of friable granules? 3.Suffer packing problems? 4. Does loading volume have a significant effect on the performance of the nautamixer? Dr. Radwa Abd El Moniem – Pharmaceutical Technology II [PHTCt 934) – Winter 2024  Mixing in Pharmaceutical Manufacturing Solid – Solid Mixing 16 Batch Mixers – Stationary shell + rotatory mixing blade Ribbon mixer Sigma blade mixer Planetary mixer Conical screw mixer  Type of mixing?  Feed & discharge?  Dead Zones ?  Cleaning?  Unmixed powder entrapped in discharge spout?  Packing problems ?  Head space?  Capacity? Dr. Radwa Abd El Moniem – Pharmaceutical Technology II [PHTCt 934) – Winter 2024  Mixing in Pharmaceutical Manufacturing Solid – Solid Mixing 17 Types of Mixers – Batch Mixers Stationary shell + Tumbling Tumbling mixers + High Shear mixers rotatory mixing Air mixers mixers agitators (granulators) blade Drum Ribbon mixer (Stationary shell (Stationary shell V-shaped Cube Sigma blade with rotating using moving air Double cone Y-cone (V- mixer mixing blade as agitator) shaped) Planetary mixers and high – speed a. Fluid bed Double cone Conical screw agitator blade) granulator Slanted Solid- solid mixing mixers Barrel mixer b. Fluid bed drier double cone Solid- liquid mixing Bowl mixer Solid- solid mixing Solid- liquid mixing Granulators Solid – solid mixing Semisolid mixing Solid- solid mixing (except ribbon) Solid- liquid mixing Dr. Radwa Abd El Moniem – Pharmaceutical Technology II [PHTCt 934) – Winter 2024  Mixing in Pharmaceutical Manufacturing Solid – Solid Mixing & Solid – liquid Mixing 18 Batch Mixers – High Shear mixers (granulators)  Since powders are neutral mixtures , have the tendency to segregate it is preferable to use one piece of equipment to carry out more than one operation, (e.g. the use of a mixer-granulator) rather than the transfer of the product between different equipment. Dr. Radwa Abd El Moniem – Pharmaceutical Technology II [PHTCt 934) – Winter 2024  Mixing in Pharmaceutical Manufacturing Solid – Solid Mixing & Solid – liquid Mixing 19 Batch Mixers – High Shear mixers (granulators) These are stationary shell mixers with a large mixer -scraper blade that mixes the ingredients, eliminates dead spots in the mixer container and presents the mixer contents to a high- speed chopper blade which mixes the ingredients. The high speed chopper is driven by a motor separate from that driving the larger more slowly rotating mixer-scraper blade, and is located at the side of the mixing bowl or chamber. How would the diosna mixer be equipped with a drying system? Dr. Radwa Abd El Moniem – Pharmaceutical Technology II [PHTCt 934) – Winter 2024  Mixing in Pharmaceutical Manufacturing Solid – Solid Mixing & Solid – liquid Mixing 20 Batch Mixers – High Shear mixers (granulators) Could it be equipped with a drying system? Advantages Disadvantages Rapid solids-solids mixing or Possible attrition of large more friable liquid-solids mixing particles or granules in a mixture Rapid granulation (6-10 min Limited batch size (second large tumbler including wet or dry) is required) Uniform particle size is obtained Potential packing problems causing i.e. that needs no further wet product contamination milling or screening Dr. Radwa Abd El Moniem – Pharmaceutical Technology II [PHTCt 934) – Winter 2024  Mixing in Pharmaceutical Manufacturing Solid – Solid Mixing & Solid – liquid Mixing 21 Batch Mixers – Air mixers Fluidized Bed Granulator/Mixer  Air mixer which has a stationary shell or body using moving air as the agitator making it more suitable for friable materials.  It is used in: Drying granules, Coating & Mixing powders  The disadvantage of fluid bed granulator is that it may segregate the very fine particles from the remainder of the mix. & powder density needs to be considered How does drying occur? Can it be used for semi-solid mixing? Could the fluid bed mixer be operated under vacuum? Dr. Radwa Abd El Moniem – Pharmaceutical Technology II [PHTCt 934) – Winter 2024  Mixing in Pharmaceutical Manufacturing Solid – Solid Mixing 22 Continuous Mixers Continuous Mixers Stationary shell + Tumbling mixers rotatory mixing Air mixer blade Zig zag blender Barrel mixer Fluid bed mixer Dr. Radwa Abd El Moniem – Pharmaceutical Technology II [PHTCt 934) – Winter 2024  Mixing in Pharmaceutical Manufacturing Solid – Solid Mixing 23 Continuous Mixers – Zigzag continuous mixer Not suitable for: -Cohesive powders -Low dose APIs -Moist powders -Prone to segregation -Increasing no. of v-shaped increases residence time increasing mixing efficiency  It is a rotating shell type, in which the shell takes the shape of several V-shaped blenders in series, which keeps the material under tumbling action. Dr. Radwa Abd El Moniem – Pharmaceutical Technology II [PHTCt 934) – Winter 2024  Mixing in Pharmaceutical Manufacturing Solid – Solid Mixing 24 Continuous Mixers – Barrel continuous mixer Powder Feed Not suitable for friable granules Hard to clean Packing gland problems Mixing Blades Mixing Shell Discharge Dr. Radwa Abd El Moniem – Pharmaceutical Technology II [PHTCt 934) – Winter 2024  Mixing in Pharmaceutical Manufacturing Solid – Solid Mixing & Solid – liquid Mixing 25 Continuous Mixers – Fluid bed continuous mixer Spraying nozzles Cont. Feed Perforated moving belt Cont. Discharge Size based Screening and separation; only Air flow granules of a specific size a reselected Large particles are milled and recycled Small particles are recycled Dr. Radwa Abd El Moniem – Pharmaceutical Technology II [PHTCt 934) – Winter 2024  Mixing in Pharmaceutical Manufacturing Liquid – Liquid Mixing 26 a) Mixing of two miscible liquids: Mixing of two miscible liquids is quite easy and occur by diffusion. Simple shaking or stirring is enough but if the liquids are not readily miscible or if they have very different viscosities then electric stirrer may be used. If a low dose API is to be mixed in a large volume of liquid, a mixer should be used b) Mixing of two immiscible liquids : When two immiscible liquids are mixed together in the presence of an emulsifying agent, an emulsion is produced. Dr. Radwa Abd El Moniem – Pharmaceutical Technology II [PHTCt 934) – Winter 2024  Mixing in Pharmaceutical Manufacturing Liquid – Liquid Mixing 27 Mechanism of mixing Molecular Bulk Transport Turbulent Flow Laminar Flow Diffusion) The movement of a It is due to random It is encountered It is the mixing of relatively large fluctuation of the with highly viscous molecules due to portion of the fluid velocity fluids Brownian motion material being mixed Macromixing leading to slow & from one location in efficient mixing. the system to another by paddles, revolving blades or other devices within the mixer. Macromixing Micromixing Dr. Radwa Abd El Moniem – Pharmaceutical Technology II [PHTCt 934) – Winter 2024  Mixing in Pharmaceutical Manufacturing Liquid – Liquid Mixing 28 Mechanism of mixing  Laminar Flow: the flow of a fluid when each particle of the fluid follows a smooth path, paths which never interfere with one another. the velocity of the fluid is constant at any point in the fluid. Turbulent flow is  Turbulent Flow: irregular flow of fluids. The velocity of obtained at high Re number. this fluid is not constant at every point producing higher mixing efficiency. Effect of factors affecting Re on turbulent low & mixing efficiency? Whether 2 fluids will show laminar or turbulent mixing depends on a factor called Reynolds number. Dr. Radwa Abd El Moniem – Pharmaceutical Technology II [PHTCt 934) – Winter 2024  Mixing in Pharmaceutical Manufacturing Liquid – Liquid Mixing 29 Mechanism of mixing Factors to consider in mixer design: According to Re number, to get high mixing efficiency: Increasing fluid velocity, will increase turbulent flow, resulting in better mixing. Increasing tube diameter/shape will increase turbulent flow, resulting in better mixing. Reducing fluid viscosity, will increase turbulent flow, resulting in better mixing. Dr. Radwa Abd El Moniem – Pharmaceutical Technology II [PHTCt 934) – Winter 2024  Mixing in Pharmaceutical Manufacturing Liquid – Liquid Mixing 30 Types of mixers Mechanical Jet Mixing In line Mixers Homogenizers Agitation Most common in They turn one of the Jet mixers uses a Instead of mixing pharmaceutical liquids into a state jet, i.e., a stream of liquids in batches in Industry consisting of extremely liquid injected at vessels, mobile 1.Impellers high velocity in the miscible components small particles distributed a.Propellers bulk of another are fed through in uniformly throughout the b.Turbines miscible liquid. line mixer creating other liquid c.Paddles turbulence in the e.g. Valve homogenizer, d.Anchors flowing fluid stream. Ultrasonic homogenizer Dr. Radwa Abd El Moniem – Pharmaceutical Technology II [PHTCt 934) – Winter 2024  Mixing in Pharmaceutical Manufacturing Liquid – Liquid Mixing 31 Types of mixers – Mechanical Agitators Turbulent Flow Radial Tangential -Rotational Axial-Longitudinal Liquidflows right angles to the shaft and parallel to the Liquid flows parallel to Liquid flows parallel to the impeller impeller. the path of impeller shaft and perpendicular to the impeller Used when mixing low to (Circular around shaft ) medium viscous fluids at high Used when mixing high Used when mixing low viscous liquids speed. viscous liquids at lower at high speed. High shear, low pumping (Flow speeds. Laminar Flow Low shear, high pumping (Flow rate). rate). Dr. Radwa Abd El Moniem – Pharmaceutical Technology II [PHTCt 934) – Winter 2024  Mixing in Pharmaceutical Manufacturing Liquid – Liquid Mixing 32 Types of mixers – Mechanical Agitators Function of each part?  Combination of the 3 principal types of flow is usually encountered in a mixing vessel.  The radial & axial flows are useful and provide the flow pattern necessary for the mixing action.  If the flow is predominantly rotational (tangential), vortex is created (which is a disadvantage in mixing), since liquid layers swirl on top one another and efficient mixing does not occur. Dr. Radwa Abd El Moniem – Pharmaceutical Technology II [PHTCt 934) – Winter 2024  Mixing in Pharmaceutical Manufacturing Liquid – Liquid Mixing 33 Types of mixers – Mechanical Agitators Vortex occurs when the shaft of the impeller is vertical and centrally located in the tank. The liquid follows a circular path around the shaft (swirled around the vessel ). Vortex Causes: 1. Inefficient mixing 2. Air enters into the material causing:  Decomposition of readily oxidized substances  Excessive frothing with certain products which may affect further processing (such as accurate filling into containers) How to avoid vortex formation? 1. Location of Impeller in tank 2. Use baffles. Dr. Radwa Abd El Moniem – Pharmaceutical Technology II [PHTCt 934) – Winter 2024  Mixing in Pharmaceutical Manufacturing Liquid – Liquid Mixing 34 Types of mixers – Mechanical Agitators How to avoid vortex formation? 1. Location of Impeller in tank The impeller can be mounted angular off  Impeller is mounted in the side of the center; tilted approximately 10-15° in a plane tank with shaft in horizontal plane. The perpendicular to direction of move. rule of thumb for this is to offset the mixer on the x-axis, 1/6th of the total tank diameter. The symmetry of the mixer is destroyed and rotational movement decreased Dr. Radwa Abd El Moniem – Pharmaceutical Technology II [PHTCt 934) – Winter 2024  Mixing in Pharmaceutical Manufacturing Liquid – Liquid Mixing 35 Types of mixers – Mechanical Agitators How to avoid vortex formation? 2. Use baffles  Baffles are long, flat plates that attach to the side of the tank. Vertical baffles are fit into the vessel which will divert the rotating fluid from its circular path into the center of the vessel.  Often used in vertical, cylindrical tanks that tend to create swirling patterns, regardless of the type of impeller being used. Baffles are often located up to 1/2 of their width from the vessel wall Why? Dr. Radwa Abd El Moniem – Pharmaceutical Technology II [PHTCt 934) – Winter 2024  Mixing in Pharmaceutical Manufacturing Liquid – Liquid Mixing 36 Types of mixers – Mechanical Agitators Types of Mechanical Agitators or Impellers 1. Anchor Type Agitator 2. Helical screw or ribbon type agitator 3. Turbine Type Agitator 4. Propeller Type Agitator 5. Paddle Type Agitator Dr. Radwa Abd El Moniem – Pharmaceutical Technology II [PHTCt 934) – Winter 2024  Mixing in Pharmaceutical Manufacturing Liquid – Liquid Mixing 37 Types of mixers – Mechanical Agitators How to choose an impeller?  1.Based on type of liquids mixed  2.Based on the application; suspensions, emulsions…etc. 1- Based on the type of liquids mixed High Viscosity Low-Intermediate viscosity liquids liquids Close Propeller Type Turbine Type Paddle/Anchor clearance Agitator Agitator Type Agitator impellers Dr. Radwa Abd El Moniem – Pharmaceutical Technology II [PHTCt 934) – Winter 2024  Mixing in Pharmaceutical Manufacturing Liquid – Liquid Mixing 38 Types of mixers – Mechanical Agitators For High Viscosity liquids Close clearance impellers  Cover the whole diameter of the mixing tank 1.Anchor Type Agitator 2.Helicalscrew or ribbon type agitator You do not need to know the labels on this slide  Dr. Radwa Abd El Moniem – Pharmaceutical Technology II [PHTCt 934) – Winter 2024  Mixing in Pharmaceutical Manufacturing Liquid – Liquid Mixing 39 Types of mixers – Mechanical Agitators Low-Intermediate viscosity liquids Propeller Type Paddle/Anchor Type Turbine Type Agitator Agitator Agitator Paddle impeller Dr. Radwa Abd El Moniem – Pharmaceutical Technology II [PHTCt 934) – Winter 2024  Mixing in Pharmaceutical Manufacturing Liquid – Liquid Mixing 40 Types of mixers – Mechanical Agitators Based on application Suspension Mixing of liquids with Mixing of liquids with Emulsification preparations different densities gases Axial (longitudinal) Flow Radial Flow Dr. Radwa Abd El Moniem – Pharmaceutical Technology II [PHTCt 934) – Winter 2024  Mixing in Pharmaceutical Manufacturing Liquid – Liquid Mixing 41 Types of mixers – Mechanical Agitators Based on application Suspension Mixing of liquids with Mixing of liquids with Emulsification preparations different densities gases Impellers that result in axial flow are pitched Impellers that result in radial flow are straight Dr. Radwa Abd El Moniem – Pharmaceutical Technology II [PHTCt 934) – Winter 2024  Mixing in Pharmaceutical Manufacturing Liquid – Liquid Mixing 42 Types of mixers – Mechanical Agitators Impeller selection depends on: 1.The application 2. Equipment size 3. Properties of materials to be mixed (e.g. viscosity and density) Dr. Radwa Abd El Moniem – Pharmaceutical Technology II [PHTCt 934) – Winter 2024  43 Pitched Axial Pitched Axial Straight Radial Pitched Axial Straight Radial Straight Radial Straight Radial Dr. Radwa Abd El Moniem – Pharmaceutical Technology II [PHTCt 934) – Winter 2024  Mixing in Pharmaceutical Manufacturing Liquid – Liquid Mixing 44 Types of mixers – Mechanical Agitators High Viscosity liquids Emulsification in large tanks Dr. Radwa Abd El Moniem – Pharmaceutical Technology II [PHTCt 934) – Winter 2024  Mixing in Pharmaceutical Manufacturing Liquid – Liquid Mixing 45 Types of mixers Mechanical Jet Mixing In line Mixers Homogenizers Agitation Most common in They turn one of the Jet mixers uses a Instead of mixing pharmaceutical liquids into a state jet, i.e., a stream of liquids in batches in Industry consisting of extremely liquid injected at vessels, mobile 1.Impellers high velocity in the miscible components small particles distributed a.Propellers bulk of another are fed through in uniformly throughout the b.Turbines miscible liquid. line mixer creating other liquid c.Paddles turbulence in the e.g. Valve homogenizer, d.Anchors flowing fluid stream. Ultrasonic homogenizer Dr. Radwa Abd El Moniem – Pharmaceutical Technology II [PHTCt 934) – Winter 2024  Mixing in Pharmaceutical Manufacturing Liquid – Liquid Mixing 46 Types of mixers – Jet mixing  No impellers  Mechanical energy required for mixing is imparted by high velocity jets  Jet mixers are driven by pumps located outside the tank.  Single or multiple jets may be provided depending on the size of the vessel and application or use.  They can be used to mix liquids, suspend solids in liquid.  They are used in large storage to maintain homogeneity of the stored liquid.  Not suitable for viscous and dense fluids Dr. Radwa Abd El Moniem – Pharmaceutical Technology II [PHTCt 934) – Winter 2024  Mixing in Pharmaceutical Manufacturing Liquid – Liquid Mixing 47 Types of mixers – Jet mixing  Tank shape, and pump type and location dictate the efficiency of mixing.  To eliminate dead zones: 1. Add multiple jets 2. Change vessel shape 3. Add baffles 4. Increasing velocity of pumped liquid Advantages: Vortex is less likely to occur than with agitated mixers (no air is introduced) Dr. Radwa Abd El Moniem – Pharmaceutical Technology II [PHTCt 934) – Winter 2024  Mixing in Pharmaceutical Manufacturing Liquid – Liquid Mixing 48 Types of mixers – Jet mixing Recirculation The Alfa Laval Rotary Jet Mixer has been designed to enable mixing of viscous and dense liquids. Rotary jet mixers effectively handle liquid mixing, Rotating spraying jet gas dispersion, powder mixing, and tank cleaning. nozzle When using the Rotary Jet Mixer, the capacity can be increased, resulting in greater productivity, and higher product quality The Rotary Jet Mixer helps reduce : Time, Cost and Power requirement Feed & Recirculation outlet Dr. Radwa Abd El Moniem – Pharmaceutical Technology II [PHTCt 934) – Winter 2024  Mixing in Pharmaceutical Manufacturing Liquid – Liquid Mixing 49 Types of mixers – In line mixers Silverson’s line of high shear In-Line mixers offers a great many advantages to the processor – a. Speed b. versatility, c. self-pumping d. aeration-free, e. guaranteed efficiency. At the heart of every mixer is Silverson’s high performance rotor/stator work head. Dr. Radwa Abd El Moniem – Pharmaceutical Technology II [PHTCt 934) – Winter 2024  Mixing in Pharmaceutical Manufacturing Liquid – Liquid Mixing 50 Types of mixers – Homogenizers  Homogenization requires the ingredients to be processed until a uniform globule or particle size in the range of 2 – 5 microns. a. Valve Homogenizer b. Ultrasonic Homogenizer Dr. Radwa Abd El Moniem – Pharmaceutical Technology II [PHTCt 934) – Winter 2024  Mixing in Pharmaceutical Manufacturing Liquid – Liquid Mixing 51 Difference between In line- mixer & Homogenizers In line mixers Homogenizers Mixing occurs when a sample is High pressure homogenization drawn in through one of the forces the sample through a mixing heads while the blades narrow space. This method uses rotate, and is then expelled at force (such as turbulence and a high velocity through an cavitation) alongside high opening in the stator. pressure to create a consistent and uniform sample. Dr. Radwa Abd El Moniem – Pharmaceutical Technology II [PHTCt 934) – Winter 2024 References 52 Ansel’s Pharmaceutical Dosage Forms and Drug Delivery Systems, 8th edition, Allen, L. V., Popovich, N. G., and Ansel, H. C., Lippincott Williams & Wilkins Publishers, ( 2005). ISBN: 0-7817-46124 Pharmaceutics the Science of Dosage Form Design, 2nd edition, M.E.Aulton. Churchill Livingstone, (2002). ISBN: 0443055173 Remington the Science and Practice of Pharmacy, 21st edition. Lippincott Williams & Wilkins, (2005). ISBN-13: 978-0781746731, ISBN-10: 0781746736 Dr. Radwa Abd El Moniem – Biopharmaceutics & Pharmacokinetics (PHTC 523) – Summer 2024  53 Links to videos HTTPS://WWW.YOUTUBE.COM/WATCH?V=ZNQRZO0ZBJE\ https://www.youtube.com/watch?v=f2giYFNhjK8 https://www.youtube.com/watch?v=Ac2s_fiTl0E HTTPS://WWW.YOUTUBE.COM/WATCH?V=PG7J-47W8I8 https://www.youtube.com/watch?v=iGFpF7HtZd HTTPS://WWW.YOUTUBE.COM/WATCH?V=NQBY-J8UZN8 A https://www.youtube.com/watch?v=EFqhkl_md0 HTTPS://WWW.YOUTUBE.COM/WATCH?V=DLLPC0_CRBE c HTTPS://WWW.YOUTUBE.COM/WATCH?V=BWA2JCARBFG https://www.youtube.com/watch?v=PECgyY4- qRc HTTPS://WWW.YOUTUBE.COM/WATCH?V=22DYQ3JEJ2I https://www.youtube.com/watch?v=EF00LgoDm HTTPS://WWW.YOUTUBE.COM/WATCH?V=X9LSNOXXHVO D4&t=28s https://youtu.be/tqVk9Dv8MhA HTTPS://WWW.YOUTUBE.COM/WATCH?V=BKMRXL4P0MI https://www.youtube.com/watch?v=HyFOgBh4a RQ HTTPS://WWW.YOUTUBE.COM/WATCH?V=JJJEOVM6TFO https://www.youtube.com/watch?v=Eh17pp6BzZ HTTPS://WWW.YOUTUBE.COM/WATCH?V=E- k C7DXZAKZM&T=1S https://www.youtube.com/watch?v=FkxH4E2LDB Y Thank you