Micrometrics means the study of particle in micron size (or) the Science and Technology of small particles is known as Micromeritics. Study involves Individual Particle size and Size Distribution Particle shape and surface area Particle volume Particle density Particle flow Particle porosity Particle associated properties introduction

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Knowledge and control of the size and the size range of particle is importance in pharmacy. Size and surface area can be related to the physical, chemical and pharmacological properties of a drug. Particle size affect its release from dosage forms that are administered orally, parenterally , rectally and topically Physical stability and pharmacologic response of suspensions, emulsion and tablets depends on particle size. It is also important in flow properties and proper mixing of granules and. powders in tableting . Both Tablets and capsules are produced using equipment which controls the mass of drug and other particles by volumetric filling. Therefore any interference with the uniformity of fill volumes may alter the mass of drug incorporated into the tablet or capsules. Thus reduce the uniformity of the medicine Application of micrometrics

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Dose uniformity: Powders with different particle sizes have different flow and packing properties which alter the volumes of powder during each encapsulation or tablet compression. Absorption and drug action: The rate of solution depends on the several factors. One factor is the particle size. Thus particles having small dimensions will tend to increase the rate of solution. For example: Griseofulvin has a low solubility by oral administration but is rapidly distributed following absorption. The solubility of Griseofulvin can be greatly increased by particle size reduction. Reduction of particles size also increase the rate of absorption of tetracycline, Aspirin and Sulphonamides . Reduction of particle size of nitrofurantoin increased the rate of absorption. Therefore the toxic effect due to rapid absorption.

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Physical stability-emulsion ,suspension due to Brownian movement particle are dispersed Particle size Particle shape Particle volume Particle surface area Particle characteristics Particle size Surface diameter d s : is the diameter of a sphere having the Same surface area as that of the asymmetric particle. Volume diameter d v : is the diameter of a sphere having same Volume as that of the asymmetric particle.

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Projected diameter d p : is the diameter of a sphere having the same area Of the asymmetric particle as observed under a microscope. Stoke diameter d st : is the diameter of an equivalent sphere undergoing Sedimentation at the same rate as the asymmetric particle. Sieve diameter d sieve : is the diameter of a sphere that passes through the Same sieve aperture as the symmetric particle. Volume-surface area d vs : is the diameter of a sphere that has same volume to surface area ratio as the asymmetric particle

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Particle shape

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Micro meter ( µ m) …… . 10 -6 meter nano meter (nm) …… .. 10 -9 meter pico meter …………… 10 -12 meter fanto meter ……………… ... 10 -15 meter particle size can be expressed Particle size of Pharmaceutical Disperse system 0.5-10 µ m--- 0.0005 - 0.010 mm Suspension, fine emulsion 10-50 µ m--- 0.010- 0.050 mm Coarse emulsion, flocculated suspension 50- 100 µ m--- 0.50- 0.100 mm Lower range of sieve range, fine powder range 150-1000 µ m--- 0.150-1.000 mm Coarse powder range 1000- 3360 µ m--- 1.000- 3.360 mm Average granule size

0 5 10 15 20 25 30 35 40 Percentage of frequency 0 10 20 30 40 Particle size(µm)

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Percent of frequency Log Particle size (µm) 2 3 5 7 10 20 30 40 0 10 20 30 40

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Particle size(µm) Cumulative % frequency under size 0 20 40 60 80 100 120 0 10 20 30 40 50

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Methods of determining particle size Particle volume measurement Coulter Counter Method Optical Microscopy Sieving Methods Sedimentation Methods Methods of determining surface area Adsorption method Air permeability method

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Sieve analysis utilizes a woven, punched or electroformed mesh often in brass, bronze or stainless steel with known aperture (hole) diameters which form a physical barrier to particles. Most sieve analyses utilize a series, stack ( Load /Mountain or nest (layer) of sieves which have the smallest mesh above a collector tray followed by meshes which get progressively coarser towards the top of the series. A sieve stack usually comprises 6-8 sieves with a progression based on a √2 or 2√2 change in diameter between adjacent aperture. Principle of Measurement Sieving method

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Powder is loaded on to the coarsest sieve of the assembled stack and the nest is subjected to mechanical vibration for, say 20 minutes After this time , the particles are considered to be retained on the sieve mesh with an aperture corresponding to the minimum or sieve diameter. A sieving time of 20 minutes is arbitrary and BS 1796 recommends sieving to be continued until less than 0.2% material passes a given sieve aperture in any 5 minutes interval This method is very simple. Not expensive Easy to operate Disadvantages Not too much precise method. Not applicable for all disperse systems. Advantages

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The Andreasen fixed-position pipette consists of a 200 mm graduate cylinder which can hold about 550 ml of suspension fluid. A pipette is located centrally in the cylinder and is held in position by a ground glass stopper so that its tip coincides with the zero level. A three way tap allows fluid to be drawn into a 10 ml reservoir which can then be emptied into a beaker or centrifuge tube. The amount of powder can be determined by weight following drying or centrifuging. Andreasen pipette

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The weight of each sample residue is therefore called the weight of undersize and the sum of the successive weight is known as the cumulative weight of undersize. It can be expressed directly in weight units or percent of the total weight of the final sediment.. The data of cumulative weight of undersize is used for the determination of particle weight distribution, number distribution,

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The weight of each sample residue is therefore called the weight of undersize and the sum of the successive weight is known as the cumulative weight of undersize. It can be expressed directly in weight units or percent of the total weight of the final sediment.. The data of cumulative weight of undersize is used for the determination of particle weight distribution, number distribution

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Fisher subsieve sizer

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A ∆Pt Є η Sw 2 Kl ( 1- Є ) 2 KOZENY-CARMAN EQUATION A= cross sectional area of the bed ∆p= pressure difference of the plug T= time of flow L=length of the sample holder Є= porosity of the powder S w 2 =surface area per gram of the powder Η =viscosity of the air K= constant V=volume of air flowing through the bed V =

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Derived properties of powder Particle size distribution and surface area-find derived properties of powder. Density of powder

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Bulk density Tapped density Bulk density, ρ = mass of a powder(w) Bulk volume( V b )

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Granule density True density Granule density= granule weight (w) Bulk volume ( V b ) True density, = weight of a powder true volume of powder

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