Objectives Definition of mixing Objectives of Mixing Types of Mixtures Mechanisms of Mixing PH 101.32

Most Commonly used operation in daily life. Mixing: Most Commonly used operation in daily life. Used in food, Plastic, Glass, Paint, Paper, fertilizer Industries. In Pharmaceutical Industry : Liquids, Viscous Liquids, Semi – solids & Solids require Mixing. PH 101.32

Introduction A true solution : An emulsion: A solution: In Pharmaceutical Industry generally Mixing is Carried out to obtain. A true solution : When two miscible liquids are mixed together An emulsion: when two immiscible liquids are mixed in presence of emulsifying agent . A solution: when Solid is dissolved in a Vehicle. PH 101.32

A Suspension: An ointment : A powder: when an insoluble solid is mixed with a vehicle in presence of a suspending agent. An ointment : When a solid or liquid is mixed with a semisolid base A powder: When two or more solid substances are mixed together PH 101.32

Definition Mixing is a process in which two or more than two components are mixed in such a way that each particle of any one ingredient lies as nearly as possible to the adjacent particle of other ingredient. PH 101.32

Objectives of Mixing To ensue uniformity of composition between mixed ingredients To enhance the Physical or chemical reactions PH 101.32

Type of Mixtures Positive Mixtures Negative Mixtures Neutral Mixtures PH 101.32

Positive Mixtures Mixed by diffusion Process No energy required Do not create any problem Eg :- Two gases or two miscible liquids. PH 101.32

Negative Mixtures Difficult to prepare. Required a higher degree of Mixing & external force Tendency to separate out unless they are continuously stirred. Eg: Suspensions & Emulsions. PH 101.32

Neutral Mixtures Static in their behaviour No tendency to mix spontaneously Do not separate out easily. Eg:- Pastes, Ointments , Mixed powder etc. PH 101.32

Mechanisms of Mixing Convective Mixing Shear Mixing Diffusive Mixing PH 101.32

Convective Mixing: Shear Mixing: Diffusive Mixing: Transfer of groups of adjacent particles from one place to another within the mixture. Shear Mixing: Shear forces created within the mass of the material by using agitator arm Diffusive Mixing: When materials tilted, gravitational forces cause the upper layers to slip & diffusion of individual particles take place PH 101.32

Objectives Liquid mixing Sub groups of liquid mixing Stages of liquid mixing Equipment of Liquid mixers: Shaker mixers Propeller mixers PH 101.33

Sub Groups of Liquid Mixing Mixing of liquids in liquids Mixing of two miscible liquids Eg: solutions Mixing of two immiscible liquids Eg: emulsions PH 101.33

Mixing of Liquids and Solids Liquids and soluble solids eg : solutions Liquids and insoluble solids eg : suspensions PH 101.33

Mixing of Liquids and Liquids Stages of mixing: Localized mixing: Shear is applied to the particles of the fluid General movement: Takes all the particles of the bulk through the nearing zone to produce uniform product PH 101.33

Small scale preparation of emulsion Suitable apparatus: mortar & pestle Shear forces produced General movement also produced Two stages of preparation of emulsions: Primary emulsion Secondary emulsion PH 101.33

Mixing of liquids & soluble solids These are homogeneous mixtures eg: solutions PH 101.33

Mixing of Liquids & Insoluble Solids These are heterogeneous mixtures eg: suspensions Suitable apparatus for small scale preparation: Mortar & pestle PH 101.33

Equipment for Liquid Mixing Shaker mixers Propeller mixers Turbine mixers Paddle mixers PH 101.33

Shaker mixers Limited use in industries: Reasons: Variable mixing efficiency Changes in viscosity Constructional characters like use of baffles Oscillatory movement : for small scale work Rotary movement : for large scale work PH 101.33

Propeller mixers Mostly widely used in industries: For liquids of low viscosity Not suitable for viscous liquids like glycerin, castor oil etc., Size of propeller small as compared to container PH 101.33

Propeller mixers Propeller rotates at a very high speed up to 8000 rpm Undesirable vortex formation & entrapment of air are resulted due to high speed of propeller Can be avoided by number of ways shown in the diagram PH 101.33

Propeller mixers Fig: 33.1 PH 101.33

Propeller mixers Fig: 33.2 PH 101.33

Propeller mixers Fig: 33.3 PH 101.33

Objective Turbine Mixers Paddle Mixers Homogenization Homogenizers PH 101.34

Turbine Mixers Consist of Circular disc impeller Rotate at lower speed than propeller Produce greater shear force than propeller Used for liquid of high viscosity Special application in preparation of emulsions PH 101.34

Fig : 34.1 PH 101.34

Paddle Mixers Paddles used as impellers Rotate at low speed of 100 r.p.m Paddles consist of blades attached to vertical shaft Blades have large surface area Effectively mix viscous liquids & semisolids PH 101.34

Paddle Mixers Fig: 34.2 PH 101.34

Homogenization Definition:- Process of conversion of coarse emulsion into colloidal state of uniform composition. Uses:- Process used for the preparation of emulsions, suspensions etc. PH 101.34

Homogenizers Equipment used for the homogenization of emulsions Principle:- Conversion Large globules in a coarse emulsion to smaller globules when passed through a narrow orifice under pressure PH 101.34

Various types of Homogenizers Hand Homogenizer (Emulsifier) Knaewood Mixer Silver son– Mixer – Emulsifier Colloid Mill PH 101.34

Emulsifier Most commonly used hand homogenizer Reduction in the globular size increasers with the speed of pumping PH 101.34

Fig: 34.3 PH 101.34

Knewood Mixer Effective mixing machine Effective mixing action because both beaters & axis rotate producing Planetary action Due to planetary action mixing of whole of the liquid is affected Different types of beaters available PH 101.34

Fig: 34.4 PH 101.34

Colloid Mill Works on the principle of shearing Consists of rotor & stator Gap between rotor stator can be adjusted from 0.005 to 0.075 cm Rotor rotates at a speed of 3000 to 20,000 r.p.m. PH 101.34

Colloid Mill Material already reduced to fine particles is fed through hopper Material thrown outward in the mill by centrifugal action. Material passes through narrow gap between rotor & stator The size of the material is reduced Fine particles collected from outlet. PH 101.34

Fig: 34.5 PH 101.34

Colloid mill Fig: 34.6 PH 101.34

Advantages Useful for preparing pharmaceutical suspensions, emulsions, lotions, ointments & creams. Capable of producing particles in micron size. Size reduction is always carried out in presence of a liquid. PH 101.34

Objectives Silver son - Mixer- Emulsifier Mixing of powders Factors affecting Mixing of powders Mechanisms of mixing. PH 101.35

Silverson Mixer – Emulsifier Consists of emulsifying head which consists of number of blades & covered with fine mesh sieve. Blades rotate at a very high speed to produce shearing action PH 101.35

Silverson Mixer – Emulsifier The emulsifying head is rotated by means of motor & immersed in the liquids to be emulsified The liquids to be mixed are sucked through fine mesh & subjected to vigorous mixing by high speed rotation of blades. PH 101.35

Silverson Mixer – Emulsifier The mixed material is then expelled out with a great force. Sucking in & forcing out of the liquid continuously goes on In this way the liquids to be mixed are made to pass repeatedly through the emulsifying head PH 101.35

Silverson Mixer – Emulsifier By this large size globules are effectively reduced to small size globules. Various sizes of mixers available Mixing capacity varies form 9 liters to 9000 liters. PH 101.35

Silverson Mixer Fig: 35.1 PH 101.35

Factors affecting mixing of powders Particle size:- Particle size & particle size distribution is important Difference in particle size can lead to segregation as smaller particles will slide past the larger ones through the voids between them. PH 101.35

Mixing of powders Powders are examples of neutral mixtures. Powder mixing is quite different from liquid mixing. Powder mixing is an operating in which 2 or more than two solids in particulate form are intermingled randomly in particles PH 101.35

Factors Affecting Mixing of Powders Particle shape: Spherical particles are easier to mix than irregular shaped particles Risk of segregation is less from particles of irregular shape Better inter - locking properties Compromise between the two is ideal for uniform mixing PH 101.35

Factors Affecting Mixing of Powders Material Density: Material with different densities are difficult to mix uniformly Heavier particles have a tendency to slide down & settle at the bottom Therefore it is necessary that the material should be of the same densities PH 101.35

Factors Affecting Mixing of Powders Particle attraction: Materials with different surface charges can lead to segregation This effect increases as the size of the particle decreases Particles with same electrostatic charges lead to aggregation of powder PH 101.35

Factors Affecting Mixing of Powders Proportion of powders to be mixed: Relative proportions of materials to be mixed play an important role Easy to mix equal quantities of two powders In cases of a smaller quantity of one powder with larger quantity of another - they are to be mixed in ascending order of their weight PH 101.35

Mechanisms of mixing Convective mixing: Mixing of powders is generally achieved by a combination of one or more of the following mechanisms Convective mixing: Takes place by the bulk transfer of groups of particles from one part of powder bed to another by means of blades or paddles PH 101.35

Mechanisms of mixing Shear mixing: Diffusive mixing: Take place due to setting up of slip planes within the mass of the material Diffusive mixing: Occurs when random movement of particles within a powder bed cause them to change their relative positions in relation to one another PH 101.35

Objectives Equipment used for mixing of powders Tumbler Mixers Agitator Mixers PH 101.36

Equipment used for Mixing of powders Tumbler Mixers Agitator mixers PH 101.36

Tumbler Mixers Construction: Consists of metallic vessels which are rotated on their axis at a slow speed. The mixing vessel are made up of stainless steel & have doors for loading and unloading of the materials. Tumbler mixers are available in a variety of shapes and sizes PH 101.36

Tumbler Mixers They are Y-cone blender, cubical blender, double cone blender, V-shaped mixer and cylindrical tumbler mixer. Y-cone, cubical and double cone blender are most popular. PH 101.36

Tumbler Mixers Y-cone blender has three arms projecting in different directions Cubical blender has a cubical shape while the double cone blender consists of a shallow drum with two conical ends. PH 101.36

Tumbler Mixers Working: Materials to be mixed are loaded into the mixing vessel which is rotated at a slow speed by means of an electric motor. Due to slow speed of rotation, the material is raised along the sides of the vessel PH 101.36

Tumbler Mixers The powder then tumbles down & mixing occurs. Vessel should not be rotated at high speed. Because the powder material shall be held along with the side of the vessel by centrifugal force & shall not fall down. Hence no mixing take place . PH 101.36

Tumbler Mixers The vessel is allowed to rotate for the required period of time . These mixers are commonly used for mixing of powders and granules during tabletting PH 101.36

Fig: 36.1 Tumbler Mixers PH 101.36

Fig: 36.2 PH 101.36

Fig:36.3 PH 101.36

Fig: 36.4 V-Cone Blender PH 101.36

Agitator powder mixers Construction: The agitator powder mixer consists of a stationary vessel in which a central shaft with helical blades is fitted. The shaft is rotated by means of an electric motor. PH 101.36

Agitator powder mixers Working: The material to be mixed is loaded into the vessel and the blades are allowed to rotate at a slow speed . The blades produce a continuous cutting and shuffling motion and cause the powder material to flow in rotational as well as transverse direction. Any powder agglomerates in the material are broken down by the shearing action that develops between the moving blade and trough. Agitated powder mixers are quite suitable for blending free flowing materials having components of preferably the same size and density. PH 101.36

Fig: 36.5 Agitated Power Mixer PH 101.36

Fig: 36.6 Agitator powder mixer PH 101.36

Objectives 1. Mixing of semisolids 2. Equipment used for semisolid mixing - Planetary mixer Sigma blade mixer Triple roller mill PH 101.37

Mixing of Semisolids Process involved depends on the properties of materials. Many semisolids form neutral mixtures. Show little tendency of segregation. Major problem is poor flow characteristics. So diffusive & convective mixing is not possible. Hence mixers with high mixing capacity are generally employed. PH 101.37

Equipment used for semi solid mixing Planetary mixers Triple roller mill PH 101.37

Fig: 37.1 Planetary Mixer PH 101.37

Fig : 37.2.Schematic Diagram of Planetary Mixer PH 101.37

Planetary Mixers Construction: Also called as change-can mixers Consists of mixing paddles fixed on the rotating arm. Arm rotates about its own axis and also travels in a circular path around the mixing vessel. Movement is alogous to that of planes. Various size and shapes of paddles available. The paddle is shaped to the size of the vessel. PH 101.37

Working: Material is loaded in the vessel Paddle is rotated at a slow speed . The small clearance between the mixing vessel and paddle provides a kneading and shearing action which ensures mixing of the material. Intermittent scrapping also required to ensure perfect and uniform mixing. PH 101.37

Fig: 37.3 Schematic Diagram of Tripple Roller Mill PH 101.37

Triple Roller Mill Various types of roller mills consisting of one or more rollers are commonly used. In pharmaceutical industry Tripple roller mill is generally preferred for mixing ointments. PH 101.37

Construction: Mill is fitted with 3 rollers which are made of hard abrasion resistant material They are arranged in close proximity to each other. They are rotated at different speeds The rollers are mounted horizontally with very small gap in between. Gap can be adjusted. The material coming between the rollers is crushed depending on the gap and also sheared by the difference in their speeds. PH 101.37

Working: Materials to be mixed are fed in the hopper though the gap Arranged to pass though the gap in between the rollers B and C where it is reduced in size. Then the material is passed between the rollers C and D, where it is further reduced in size. Smooth mixture is obtained . PH 101.37

Working The Gap between rollers C and D is usually less that the gap between B and C. After passing the material between rollers C and D, the smoothened mixture is continuously removed from roller D by means of scrapper E. From there, it is collected in a receiver PH 101.37

Uses Triple Rollers mill is often used for mixing of solid ingredients in semisolid base like Ointments PH 101.37

Objectives 1. What is meant by “Mixing” & “Homogenization” 2. Mixers used in mixing of liquids, solids and semisolids PH 101.38

Definition of Mixing Mixing: In pharmaceutical Industry: A process in which two or more than components are mixed in such a way that each particle of any one ingredient lies as nearly as possible to the adjacent particle of other ingredient. In pharmaceutical Industry: Process of mixing is used in the formulation of solutions, emulsions, suspensions, powders, ointments and creams PH 101.38

Type of mixtures: Mechanisms of mixing: 1. Positive mixtures eg; Two miscible Liquids 2. Negative mixtures eg: Suspensions & Emulsions 3. Neutral mixtures eg: Pastes & ointments Mechanisms of mixing: Convective mixing Shear mixing Diffusive mixing PH 101.38

Liquid Mixing Mixing of liquids & liquids: Mixing of liquids & Solids: Mixing of two miscible liquids Eg: Solutions Mixing of two immiscible liquids Eg: Emulsions Mixing of liquids & Solids: Mixing of liquids & soluble solids Eg: Solutions Mixing of liquids & insoluble solids Eg: Suspensions. PH 101.38

Liquid Mixing On small scale emulsions & suspensions can be prepared by using mortar & pestle Emulsions are prepared in 2 stages : primary emulsion and secondary emulsion. PH 101.38

Equipment used for liquid mixing Propeller Mixers Paddle Mixers Shaker Mixers Turbine Mixers PH 101.38

Propeller Mixer These are used for mixing liquids of low viscosity Propeller rotates at a very high speed up to 8000 rpm Turbine mixers used for liquids of low high viscosity and rotate at lower speed than propellers In paddle mixers, paddles rotate at low speed of 100rpm Effectively mix viscous liquids & semisolids PH 101.38

Homogenization Definition: Various types of Homogenizers: Process of conversion of coarse emulsion into colloidal state of uniform composition. Equipment used for this process – homogenizers Various types of Homogenizers: Hand Homogenizer Silverson – mixer – emulsifier Colloid mill PH 101.38

Principle involved in homogenizers Conversion of large globules in a coarse emulsion to smaller globules when passed through a narrow orifice under pressure. Colloid mill: Used for preparing suspensions , emulsions lotions, ointments and creams. Widely used homogenizers are Silverson mixer- emulsifier and colloid mill PH 101.38

Mixing of powders: Factors affecting mixing of powders Particle size , particle shape , material density, particle attraction, proportion of powders to be mixed. Mechanisms of mixing : Convective mixing , shear mixing, diffusive mixing PH 101.38

Equipment used for mixing of powders: Tumbler mixers, Agitator mixers, Double cone mixer Semisolid mixing: Equipment used for semisolid mixing Planetary mixer Triple roller mill PH 101.38

Most commonly used mixers for mixing are semisolids Planetary mixers & sigma blade mixers Triple roller mill is often used for incorporating solid medicaments into ointment bases PH 101.38