coarse dispersions

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Coarse dispersion

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Suspensions A pharmaceutical suspension is a coarse dispersion in which insoluble solid particles are dispersed in a liquid medium. In soluble particle size 10 to 1000 µm The liquid medium water or water based In soluble particle Liquid medium

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Solid space Liquid space S/L interspaces Interfacial Tension In soluble particle Liquid medium Interfacial Tension Add Surfactant Ex- Tween 80,20,40 Span 20,60 SLS

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PROPERTIES OF IDEAL SUSPENSION They don’t settle rapidly Dose precision lack Should not form a hard cake Particle redisperse difficult

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Easily redisperse on moderate shaking Should be easily poured from the bottle( proper viscosity ) Uniform distribution of particle Dose precision

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Particle size and viscosity of suspension-easily injected through the needle

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Topical suspension-should leave a film on skin? Uniform distribution & Complete recovery from disease Should have an acceptable taste

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Suspension resist to microbial attack (preservative added) Degradation of suspension It should have good self life Proper therapeutic action Microbial contamination

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Classification of suspension Dilute suspension-2 to 10% solids Concentrated suspension- more than 50% Cortisone acetate prednisolone acetate Eg: zinc oxide suspension

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Deflocculated suspensi on Flocculated suspension Supernatant remain cloudy Supernatant is clear Pleasant appearance? Uniform distribution of particle Unsightly sediment and Clear supernatant layer Particle experience repulsive force repulsion attraction Particle experience attractive force

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After min After hrs After week After min After hrs After week Hard cake particle size less Bioavailability more sedimentation rate low particle size more Bioavailability less compare with deflocculated suspension sedimentation rate high Particles are separate entities Particles are loose aggregates

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Shake-The Hard cake cannot be redispersed Shake-The settled particle easily redispersed Sedimentation – take more time Sedimentation – take less time Particle aggregation by strong force Particle aggregation By weak vander waals force Because particle size is smaller Because particle size is bigger Less physical stability More physical stability

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Controlled flocculation Controlled flocculation (flocculated suspension) can be achieved by slow addition of flocculation agents such as Electrolyte Surfactant polymers Flocs do no’t form hard cake (loosely aggregated) and redisperse Immediately when small force is applied

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ELECTROLYTE + + + + + + + + Bi Bi Positive charge Repulsive force Bismuth sub nitrate in water Zeta potential 25 mv (Particle become deflocculated) Gradually add electrolyte (or) Flocculating agents KH 2 PO 4 PO 4 - + + + + Bi + + + + Bi - - - - + + + + + + + + Bi Bi - - - - Zeta potential Further addition of Negative charge Negative Charge - - - - Zeta potential positive

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+ + - - + + - - + + - - + + - - Bi Bi + + - - + + - - + + - - + + - - Bi Bi + + - - + + - - + + - - + + - - Bi Bi - - Zeta potential zero Positive charge = negative charge Maximum sedimentation Volume (flocculation) Further addition of Negative charge Zeta potential further Decease (negative) - - Further addition of Negative charge - - - - Negative charge dominate Repulsive force ((Particle become deflocculated)

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The zeta potential is defined as the difference in potential between the surface of the tightly bound layer (shear plane) and electro-neutral region of the solution. Zeta Potential

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As the potential drops off rapidly at first , followed more gradual decrease as the distance from the surface increases . This is because the counter ions close to the surface acts as a screen that reduce the electrostatic attraction between the charged surface and those counter ions further away from the surface. Zeta potential has practical application in stability of systems containing dispersed particles . If the zeta potential is reduced below a certain value , the attractive forces exceed the repulsive forces, and the particles come together. This phenomenon is known as flocculation. The flocculated suspension is one in which zeta potential of particle is -20 to +20 mV. Thus the phenomenon of flocculation and de flocculation depends on zeta potential carried by particles .

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V u /V o + + + + + + + - - - - - - - - - + + + + - - - - KH 2 PO 4 Apprarent zeta potential + - Sedimentation volume curve The flocculated suspension is one in which zeta potential of particle is -20 to +20 mV. Zeta potential curve

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+ + + + + + + + SO 4 SO 4 SO 4 SO 4 Head portion absorb on solid surface Tail outwards surfactant Tail Tail Head surfactants Surfactant reduce interfacial tension Improve the dispersion of particle Addition of surfactant (concentration) to get the flocculation is difficult. The head portions absorb on the solid surface and the tail project outwards And form bridges between the particle Ex.SLS Solid particle

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Polymer Molecule polymers These act as flocculating agents because a part of the polymer chain get adsorbed on the particle surface with the remaining portion projecting out into the dispersion medium.

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EVALUTION OF SUSPENTION Vu Vo 100 ml 50 ml Sedimentation Parameters Sedimentation volume (F) for flocculated suspensions: Definition: Sedimentation volume is a ratio of the final or ultimate volume of sediment (Vu) to the original (initial) volume of sediment (Vo) before settling. F = Vu / Vo Where, Vu = final or ultimate volume of sediment Vo = original (initial) volume of suspension before settling.

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F has values ranging from less than one to greater than one. Normally F < 1 When F < 1 Vu < Vo When F =1 Vu = Vo The system is in flocculated equilibrium and show no clear supernatant on standing. When F > 1 Vu > Vo Sediment volume is greater than the original volume due to the network of flocs formed in the suspension and so loose and fluffy sediment

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F=0.5 F=1 F=1.5 F < 1 Vu < Vo F =1 Vu = Vo F > 1 Vu > Vo

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Sedimentation volume F Ideal curve Time 1 2 3 4 5 6 7 0.5 0 1.0 Flow chart of formulation of suspension

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When the total volume of both the flocculated and the deflocculated suspensions are same; ß = (Vu)floc / (Vu) defloc β = ultimate sediment volume of flocculated susp ultimate sediment volume of deflocculated susp The minimum value of ß is 1; this is the case when the sedimentation volume of the flocculated suspension is equal to the sedimentation volume of deflocculated suspension. ß is more fundamental parameter than F since it relates the volume of flocculated sediment to that in a deflocculated system

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Brownian Movement (Drunken walk) Brownian movement of particle prevents sedimentation by keeping the dispersed material in random motion. Brownian movement depends on the density of dispersed phase and the density and viscosity of the disperse medium .

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Brownian movement can be observed , If particle size is about 2 to 5mm, When the density of particle & viscosity of medium are favorable.

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FORMULATION OF SUSPENSIONS The formulation of a suspension depends on whether the suspension is flocculated or deflocculated. Three approaches are commonly involved Use of structured vehicle Use of controlled flocculation Combination of both of the methods

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Preparation of suspension

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Structured vehicles called also thickening or suspending agents. They are aqueous solutions of natural and synthetic gums. These are used to increase the viscosity of the suspension. It is applicable only to deflocculated suspensions. E.g. methyl cellulose, sodium carboxy methyl cellulose, acacia, gelatin and tragacanth. Structured vehicle

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These structured vehicles entrapped the particle and reduces the sedimentation of particles. Thus, the use of deflocculated particles in a structure vehicle may form solid hard cake upon long storag e. Too high viscosity is not desirable as: a) It causes difficulty in pouring and administration. b) It may affect drug absorption since they adsorb on the surface of particle and suppress the dissolution rate. Structured vehicle is not useful for Parenteral suspension because they may create problem in syringeability due to high viscosity.

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Wetting agents They are added to disperse solids in continuous liquid phase. Flocculating agents They are added to floc the drug particles Thickeners They are added to increase the viscosity of suspension. Buffers and pH adjusting agents They are added to stabilize the suspension to a desired pH range. Osmotic agents They are added to adjust osmotic pressure comparable to biological fluid. Coloring agents They are added to impart desired color to suspension and improve elegance. Preservatives They are added to prevent microbial growth. External liquid vehicle They are added to construct structure of the final suspension.

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Advantages And Disadvantages . Suspension can improve chemical stability of certain drug. E.g. Procaine penicillin G. Drug in suspension exhibits higher rate of bioavailability than other dosage forms. Solution > Suspension > Capsule > Compressed Tablet > Coated tablet Duration and onset of action can be controlled. E.g. Protamine Zinc-Insulin suspension. Suspension can mask the unpleasant/ bitter taste of drug. E.g. Chloramphenicol

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Disadvantages Physical stability , sedimentation and compaction can causes problems. It is bulky sufficient care must be taken during handling and transport. It is difficult to formulate. Uniform and accurate dose can not be achieved unless suspension are packed in unit dosage form.

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Applications Suspension is usually applicable for drug which is insoluble (or ) poorly soluble. E.g. Prednisolone suspension To prevent degradation of drug or to improve stability of drug. E.g. Oxy tetracycline suspension To mask the taste of bitter of unpleasant drug . E.g. Chloramphenicol palmitate suspension Suspension of drug can be formulated for topical application e.g. Calamine lotion

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Suspension can be formulated for parentral application in order to control rate of drug absorption . E.g. penicillin procaine Vaccines as a immunizing agent are often formulated as suspension. E.g. Cholera vaccine X-ray contrast agent are also formulated as suspension . eg: Barium sulphate for examination of alimentary tract.

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