Published on March 10, 2014
PowerPoint Presentation: Pharmaceutical suspension Vikrant Saluja Faculty of Pharmaceutical Sciences PCTE Group of Institutes, Ludhiana Punjab, India PowerPoint Presentation: A suspension is a dispersion of finely divided, insoluble solid particles(the disperse phase) in a fluid (the dispersion medium or continuous phase). Or Suspensions are the biphasic liquid dosage form of medicament in which the finely divided solid particles ranging from 0.5 to 5µ are dispersed in a liquid or semisolid vehicle. Or Suspensions are heterogenous system consisting of 2 phases. PowerPoint Presentation: Physical properties of well formulated suspensions The sediment or creaming produced on storage, if any, must be easily resuspended by moderate agitation of the container. The product must remain sufficiently homogenous for at least the period between shaking the container and removing the required amount. The product may be required to be thickened in order to reduce the rate of settling of the particles The resulting viscosity must not be so high that removal of the product from the container and transfer to the site of application are difficult. Any suspended particles should be small and uniformly sized in order to give a smooth, elegant product, free from a gritty texture. PowerPoint Presentation: PHARMACEUTICAL APPLICATIONS OF SUSPENSIONS 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. Oxytetracycline suspension. Suspension can mask the unpleasant/ bitter taste of drug. E.g. Chloramphenicol palmitate For topical application . They are designed to leave a light deposit of the active agent on the skin after quick evaporation of the dispersion medium. For parenteral administration in order to control the rate of absorption of the drug. Vaccines for the induction of immunity are often formulated as dispersions of killed microorganisms. Some X-ray contrast media are formulated in suspension form. PowerPoint Presentation: Classification Based On Route Of Administration Oral suspension Externally applied suspension Parenteral suspension Based On Proportion Of Solid Particles Dilute suspension (2 to10%w/v solid) Concentrated suspension (50%w/v solid) Based On Electrokinetic Nature Of Solid Particles Flocculated suspension Deflocculated suspension Based On Size Of Solid Particles Colloidal suspension (< 1 micron) Coarse suspension (>1 micron) Nano suspension (10 -100 nm) PowerPoint Presentation: Theory of Suspensions Sedimentation means settling of particle or floccules under gravitational force in dispersion system. Velocity of sedimentation expressed by Stoke’s equation V= 2r 2 ( ρ s- ρ o ) g or V= d 2 ( ρ s- ρ o ) g 9 18 Where, v sed. = sedimentation velocity in cm / sec d = Diameter of particle r = radius of particle ρ s = density of disperse phase ρ o = density of disperse media g = acceleration due to gravity η = viscosity of disperse medium in poise PowerPoint Presentation: Sedimentation Parameters Sedimentation volume (F) F = V u / V O -------------- (A) Where, V u = final or ultimate volume of sediment V O = original volume of suspension before settling. Sedimentation volume can have values ranging from less than 1 to greater than1; F is normally less than 1. F=1,such product is said to be in flocculation equilibrium, and show no clear supernatant on standing PowerPoint Presentation: ß = F floc / F defloc Degree of flocculation (β) It is the ratio of the sedimentation volume of the flocculated suspension ,F , to the sedimentation volume of the deflocculated suspension, F∞ The minimum value of ß is 1,when flocculated suspension sedimentation volume is equal to the sedimentation volume of deflocculated suspension. PowerPoint Presentation: Flocculated and deflocculated systems Flocculated Deflocculated Much more rapid rate of sedimentation The rate of sedimentation is slow. Particles form loose aggregates and form network like structures Individual particles exists as separate entity. The supernatant is clear. The supernatant is cloudy. The sediment can be easily redisperse on moderate shaking. The sediment can be very difficult to redisperse. PowerPoint Presentation: FORMULATION OF SUSPENSIONS Components Function API Active drug substances 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 They are added to stabilize the suspension to a desired pH range. Coloring agents They are added to impart desired color to suspension and improve elegance. Preservatives They are added to prevent microbial growth. PowerPoint Presentation: Wetting agents : They are added to disperse solids in continuous liquid phase. Surface-active agents Hydrophilic colloids Solvents PowerPoint Presentation: Wetting agents Surface-active agents Non-ionic surfactants are most commonly used as wetting agents in pharmaceutical suspension. Surfactants possessing an HLB value between about 7 and 9 would be suitable for use as wetting agents. Used at concentrations of up to about 0.05-0.5% . For oral use , the polysorbates (Tweens) and sorbitan esters (Spans). For external application , sodium lauryl sulphate, sodium dioctylsulphosuccinate and quillaia extract. For parenteral administration, polysorbates, some of the poloxamers (polyoxyethylene/polyoxypropylene copolymers) and lecithin. Disadvantages They have foaming tendencies. The possible formation of a deflocculated system, which may not be required. Some surfactants such as polysorbate 80 interact with preservatives such as methyl paraben and reduce antimicrobial activity. PowerPoint Presentation: Wetting agents Hydrophilic colloids Behave as protective colloids by coating the solid hydrophobic particles with a multimolecular layer. This will impart a hydrophilic character to the solid and so promote wetting. Also used as suspending agents . These materials include acacia, bentonite, tragacanth, alginates, xanthan gum and cellulose derivatives Solvents Materials such as alcohol, glycerol and glycol s, which are water miscible, will reduce the interfacial tension. PowerPoint Presentation: Flocculating agents Electrolytes Surfactants Polymeric flocculating agents PowerPoint Presentation: Electrolytes The addition of an inorganic electrolyte to an aqueous suspension will alter the zeta potential of the dispersed particles and, if this value is lowered sufficiently, flocculation may occur. The most widely used electrolytes include the sodium salts of acetates, phosphates and citrates Care must be taken not to add excessive electrolyte Surfactants Ionic surface-active agents may also cause flocculation by neutralizing the charge on each particle Polymeric flocculating agents Their linear branched-chain molecules form a gel-like network within the system and become adsorbed on to the surfaces of the dispersed particles, thus holding them in a flocculated state. Starch, alginates, cellulose derivatives, tragacanth, carbomers and silicates PowerPoint Presentation: Viscosity modifiers Polysaccharides Acacia Tragacanth Alginates Starch Xanthan gum (Keltrol) Water-soluble celluloses Methylcellulose (Celacol, Methocel) Hydroxyethylcellulose (Natrosol) Sodium carboxymethylcellulose (Carmellose sodium) Microcrystalline cellulose Hydrated silicates Bentonite Magnesium aluminium silicate (Veegum) Hectorite Colloidal silicon dioxide (Aerosil) Carbomers (carboxypolymethylene) METHODS OF DISPENSING SUSPENSIONS : METHODS OF DISPENSING SUSPENSIONS 1.Suspensions containing diffusible solids 2.Suspensions containing indiffusible solids 3.Suspensions containing precipitate forming liquids 4.Suspensions produced by chemical reactions PowerPoint Presentation: Suspensions containing diffusible solids Contains insoluble drug particles which are light in weight and readily mix with water and remain suspended throughout the liquid for sufficient period of time after shaking Example : calcium carbonate, magnesium trisilicate , rhubarb powder ,light kaolin General method of dispensing Powder all the solid ingredients and add enough vehicle to form a smooth cream Add more of vehicle to make it pourable Remove if any foreign particle present by passing through muslin cloth Rinse the mortar and pestle with successive volume of vehicle untill they are quite clean Add if any liquid ingredients Add more of vehicle to adjust the final volume and mix thorughly by shaking the bottle Example: Kaolin mixture PowerPoint Presentation: Suspensions containing indiffusible solids Contain substances which do not dissolve in water and do not remain evenly distributed in the vehicle for sufficient period of time Example: calamine , zinc oxide ,hydro cortisone, aspirin,phenobarbitone General method of dispensing Powder and mix all the solid ingredients and add compound tragacanth powder Measure ¾ th of the vehicle and triturate to form a smooth cream Remove if any foreign particle present by passing through muslin cloth Rinse the mortar and pestle with successive volume of vehicle until they are quite clean Add if any liquid ingredients Add more of vehicle to adjust the final volume Example: succinyl sulphathiazole mixture PowerPoint Presentation: Suspensions containing precipitate forming liquids Contains liquid substances that is precipitated on addition of water. These liquid substances are insoluble and indiffusible and it is diificult to redisperse on shaking .Example: compound benzoin tincture,, myrrh tincture General method of dispensing(using tragacanth powder) Powder and mix all the indiffusible and diffusible solid ingredients Add compound tragacanth powder and mix Measure half of the vehicle and incorporate small amount of it to the powders to form a smooth cream and add remaining part of the vehicle Add precipitate forming liquid in a slow stream in the centre of the cream with rapid stirring Dissolve the soluble ingredient if present in the vehilcle and add slowly with constant stirring Remove if any foreign particle present by passing through muslin cloth Remaining steps are Same as that of dispensing for suspension containing diffusible solids General method of dispensing(using tragacanth mucilage) Tragacanth mucilage is used when the vehicle is water or chloroform water Mix the tragacanth mucilage with an equal volume of the vehicle Add precipitate forming liquid in a slow stream in the centre of the mucilage with constant stirring Dissolve the solid substance if any, in about ¼ th of the vehicle and mix it with the above mixture Remaining steps are Same as that of dispensing for suspension containing precipitate forming liquid using compound trgacanth powder PowerPoint Presentation: Suspensions produced by chemical reactions Some of the suspensions are prepared by the chemical reactions between the ingredients used in the formulations. In this reactants are highly diluted and mixed together to form very finely divided precipitates that can be easily distributed throughout the liquid by shaking. The precipitate so formed are diffusible in nature. Hence there is no need of adding any suspending agent. Example:sulphurated potash and zinc sulphate mixture PowerPoint Presentation: Evaluation of Suspension Sedimentation method Rheological method Electro kinetic method Micromeritic method PowerPoint Presentation: Sedimentation method Two parameters Sedimentation volume , F = V u /V o V u = final sediment volume V o = initial dispersion volume want F =1 Degree of flocculation , = V u /V u V u final sediment volume of deflocculated suspension The determination of sedimentation volume provides a qualitative means of evaluation. A quantitative knowledge is obtained by determining the degree of flocculation. PowerPoint Presentation: Rheological method Settling behaviour The arrangement of the vehicle and the particle structural features. Brookfield viscometer mounted on helibath stand and using T-bar spindle. T-bar spindle is made to descend slowly into the suspension and the dial reading on the viscometer is then a measure of the resistance the spindle meets at various level. PowerPoint Presentation: This technique also indicates in which level of the suspension the structure is greater owing to particle agglomeration. The dial reading is plotted against the number of turns of the spindle. The better suspension show a lesser rate of increase of dial reading with spindle turns, i.e. the curve is horizontal for long period PowerPoint Presentation: Electro kinetic method Measurement of Zeta-potential using Microelectrophoresis apparatus It shows the stability of a disperse system Zeta Potential [mV] Stability behavior of the colloid: 0 to ± 5, Rapid coagulation or flocculation ± 10 to ± 30 Incipient instability ± 30 to ± 40 Moderate stability ± 40 to ± 60 Good stability more than ± 61 Excellent stability PowerPoint Presentation: The particle are placed in an electrical field between two electrodes, the voltage can be adjusted and tracked under the microscope. Their velocity is determined The relation of velocity to voltage determine the zeta-potential It is worthwhile to occasionally check the zeta-potential in a stability check of suspension PowerPoint Presentation: Micromeritic method Freeze-thaw cycling technique Stressing suspension for stability testing purposes. This treatment promotes particle growth and may indicate the probable future state of affairs after long storage at room temperature. Dynamic light scattering Known as Photon correlation spectroscopy (PCS) works by first measuring the scattered light intensity at one angle. 1 nm – 6 µm Microscopic method No of particles to be counted from 300- 500 particles 0.2 – 100 µm
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