interfacial phenomena 2


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spring 2008


By: pazmor56 (117 month(s) ago)

thanks this will be very helpful in my classs

Presentation Transcript

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The flow properties of powder plays an important role in dosage form manufacturing process. Importance of Flow-property studies of powder material 1.Weight uniformity 2.Content uniformity 3.Hardness 4.Disintegration 5.Speed of production 6.Scientific design of formulations and processing equipment FACTORS INFLUENCING THE FLOW OF POWDERS 1.Particle size 2.Size distribution 3.Particle shape 4.Moisture and static charge 5.Electrostatic effects 6.Powder cohesion and storage compaction 7.Effect of temperature

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PARTICLE SIZE If size (or) dimensions of particles altered Particles change in nature flow of particles changed

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In general larger particle flow faster than smaller particles? Particles less than 100µm in diameter cohesive Poor flow Particles above 1000µm in diameter Free Good flow

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SIZE DISTRIBUTION Size distribution is carried out by using proper amounts of fines. PARTICLE SHAPE AND SURFACE MORPHOLOGY The irregular shapes of particles flow become slowly. Scaning electron microscope. The mixtures containing irregularly shaped particles segregated slowly. The flowability of powders increase with increasing sphercity, indicted by shape index ῳ and measured by image analyser.

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MOISTURE AND STATIC CHARGE The effect of moisture on flowability of particles varies from powder to powder. The particles become cohesive due to moisture absorption. Absorbed moisture in solids can exist in two forms1.unbound state2.As a part of crystal structure The effect of moisture on flow of powder measured by determination of tensile strength.

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ELECTROSTATIC EFFECTS The charged material show poorer flow than uncharged material. Particles acquire static charge Grinding Attrition collision mixing sieving Moisture Particle-wall collisions, particle-particle collisions, or particle fragmentatoin Electro static charge may be possitive or negative. +ve particles plastic surfaces -ve particles metal or glass surfaces

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POWDER COHESION AND STORAGE COMPACTION A solid remains at rest or storage in a hopper or bin , it can become more cohesive and difficult to flow. Flow chacteristics depends on Intrinsic cohesiveness of the material Temperature of storage Hopper and bin load levels Time of storage Vibratory forces

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METHODS OF IMPROVING THE FLOW PROPERTIES OF POWDERS 1.INCREASING THE AVERAGE PARTICLE SIZE Large particles are less cohesive and fast flow Granules are commonly used in tablet manfacture 2. PRODUCING THE POWDER IN THE FORM OF SPHERICAL PARTICLE Spherical partcile flows easily Produced by spray drying 3. USE OF GLIDANT Improve the flow properties of powder and granules Ex:- colloidal silicone, talc, and starch

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MECHANISM OF GLIDANT ACTION Dispersion of static charge Adsorption of gases and vapours in the system Physical seperation of particles Adsorption of Glidant particles to granulation surfaces Coat the host particles completely EFFECT OF GLIDANT Particle size and shape Degree of mixing Concentration of glidant Moisture content

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MEASUREMENT OF FLOW PROPERTIES 1. Angle of repose 2. Compressibility index 3. Shear cell method 4. Hopper flow rate

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1. ANGLE OF REPOSE:- Angle of repose is defined as the angle of the free surface of a pile or heap of powder to the horizontal plane. Characterize the flow properties of solids. If material is not cohesive Flows well Low heap If material is cohesive Poor flow High heap

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The standard method include pouring the powder onto the plat surface and measuring the angle of the resulting heap tan  = h/r

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Tan = h/r h = height of the heap r = radius of the heap Protractor is commonly used to measure the base and height of the heap.

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2. COMPRESSIBILITY INDEX:- It demonstrates the relation between the flow and compressibility of Powder. %Compressibility = (tapped density – poured density /tapped density ) 100

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HAUSNER RATIO Hausner predict the flow properties of powder by using interparticle friction Hausner ratio = tapped density /poured density

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3. SHEAR CELL DETERMINATIONS :- Characterize the flowability from the behavior of powder in a shear cell Sand witch of powder The powder bed was subjected to shear and its applied load for shear also noted Graph plotted between shear stress and applied load Flow factor can be obtained by determining the reciprocal slope of a curve.

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4. HOPPER FLOW RATE Simplest method Simple shutter is placed over the hopper outlet and powder is filled The shutter is then removed and time taken for complete discharge of powder is taken The ratio of powder mass to time taken for complete discharge gives flow rate FLOW RATE = POWDER MASS / TIME PERIOD

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SEGREGATION segregation × mixing segregation Difference in mobility of mixture components Differences in partical size,shape,density and surface characteristics FACTORS FOR SEGREGATION IN POWDER BED un uniform particles Vibration Mixing and handling Free flowing particles or cohesion less

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PARTICLE PROPERTIES THAT EFFECT SEGREGATION 1.particle size 2.particle density 3. particle shape 1.PARTICLE SIZE Difference in particle size is the main cause of segregation smaller particles void spaces of larger particles percolation segregation

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Kinetic energy of larger particles > kinetic energy of smaller particles Larger particles move greater distance than smaller particles Trajectory segregation

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During mixing very small particles are blown upward by turbulent air The small particles or dust will sediment and subsequently form a layer on top of the coarse particles Elutriation segregation or dusting out

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2.PARTICLE DENSITY More denser particles segregate faster than less denser than particles Difference in particle density results in trajectory segregation 3.PARTICLE SHAPE Intensity of segregation is more in spherical particles than non spherical particles

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APPROACHES TO RECTIFY SEGREGATION Selection of particular size fraction Milling of components Controlled crystallization Selection of similar densities of excipients and active components Production of ordered mix Granulation of powder mixture Prevent the movement and vibration of powder bed

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SOLID STATE STABILITY Various stability studies conducted are 1.Elevated temperature studies 2.Under humidity condition studies 3.Photolytic stability 4.Stability to oxidation

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ELEVATED TEMPERATURE STUDIES The elevated temperatures most commonly used are 50ºc ,60ºc,70ºc, and 85ºc,121ºc Conduct the same experiments at room temperature(30ºc,70%RH) Samples may be done at 3 month intervals during the first year 6 month intervals during the second, and yearly thereafter The samples stored at high temperatures are examined for physical and chemical changes at frequent intervals and any change, when compared to appropriate control (usually sample stored at 5 ºc or 20 ºc To confirm the results obtained from accelerated stability studies and room temperature The drug content is estimated by using a stability indicating assay method

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STABILITY UNDER HUMIDITY CONDITIONS In the presence of moisture many drugs hydrolyze or oxidize by react with other ingredients. Expose the solid drug to different relative humidity conditions Controlled humidity environment can be produced by using laboratory desicator containing saturation solutions of various salts

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PHOTOLYTIC STABILITY Many drug substances are fade or darken on exposure to light Extent of degradation is small and limited to exposed surface itself Protected by 1.Stored in amber colour glass or opaque container 2.By incorporating photostable dye exposure of the drug substance to 400 and 900 foot candles (fc) of illumination for 2to 4 weeks Over these period samples are withdrawn and examine for any loos of colour and Chemical stability and compared with that of samples stored under same conditions but protected from light Change in appearance is quantified by using spectroscopic methods

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STABILITY TO OXIDATION Stability to oxidation was carried out by using the hydrogen peroxide in the concentration range of 3to 30% some drugs extensive degradation is seen when exposed to even 3% of hydrogen peroxide for very shorter time period at room temperature Some drugs exposure to high concentration of hydrogen peroxide even under extreme condition does not cause any significant degradation Usually 40% oxygen atmosphere allows for a rapid evaluations Results should be compared against those obtained under ambient atmosphere

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BIBLIOGRAPHY J.T. Carstensen, Principles and practices of drug stability, “solid state stability” by markel,2nd edition.1995. 2. Stephen. A.howard, Flow properties of solids, “ Encyclopedia of pharmaceutical technology” by markel dekker,2nd edition, volume-2, page no-1264 -1283 3. S.J. Carter, The flow properties of powders and granules, “Tutorial pharmacy” by CBS Publishers and distributors, 6th edition, 2000, pg no-223 -229 4. N.K. Jain, Flow ,cohesiveness and compressibility, “Professional pharmacy” by vaallabh prakashan, 5th edition,1998 pg no-145-147 5. Harry G. Brittain, Physico chemical properties, ,”Physical characterization of pharmaceutical solids” by markel,1995 6.C.V.S Subramanyam, Drug stability, “physical pharmaceutics “by vallabh prakashan,5th edition,2000,

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Thank you

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