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M.Pharm.(Ph.D.) Associate Professor. Submitted by: MAHALAKSHMI YADAV GS M.PHARM 1 st year VIGNAN PHARMACY COLLEGE , GUNTUR.PowerPoint Presentation: 1.RELEASE AND DISSOLUTION: Particle size influence the release of a drug from a dosage form.If particle size is less, then its surface area is high and it allows intimate contact of the drug with the dissolution fluids invivo and increases the drug solubility and dissolution. 2.ABSORTION & DRUG ACTION: Higher the dissolution, faster the absorption & hence quicker & greater the drug action. 3.PHYSICAL STABILITY: The particle size in a formulation influences the physical stability of the suspensions & emulsions. smaller the size of the particle ,better the physical stability of the dosage form. 4.DOSE UNIFORMITY: Good flow properties of granules and powders are important in manufacturing of tablets and Capsules. The knowledge and control of the size of particles is of importance in pharmacy and materials science . The size and surface area of the particle can be related to the physical , chemical and pharmacological properties of drugs .PowerPoint Presentation: AS THE PARTICLE SIZE DECREASES , SURFACE AREA INCREASES .Why We Care About Particle Size and Surface Area: Why We Care About Particle Size and Surface Area These characteristics control many properties of materials: Flow ability; “Filter-ability” Viscosity- Rheology ; Agglomeration; Dusting tendency; Settling rate; Activity/Reactivity rate (e.g. of catalyst); Dissolution rate (of pharmaceutical); Gas absorption; Hydration rate (of cement); Moisture absorption; Entry into lungs (shape dependency too); Combustion rate (of fuel) Etc…PowerPoint Presentation: Particle size ranges If Particle size decrease means the rate of reaction , dissolution, surface area increases. Range in µm matter 0.5- 10 Suspensions and emulsions 50-100 Fine powder 150-1000 Coarse powder 1000-3360 Granule sizePowerPoint Presentation: Particle size distribution The particle size distribution ("PSD") of a powder defines the relative amounts of particles present, sorted according to size. The method used to determine PSD is called “Particle size analysis “, and the apparatus as particle size analyzer. Significance of PSD The PSD of a material can be important in understanding its physical and chemical properties. It affects the reactivity of solids participating in chemical reactions, and Needs to be tightly controlled in many industrial products such as the manufacture of printer toner , cosmetics , pharmaceutical , etcPowerPoint Presentation: Particle size Since most of the particles are irregular it is difficult to express their size in a meaningful diameter, hence equivalent diameters are introduced. Equivalent diameters: i. surface diameter d s : Is the diameter of a sphere having the same surface area as that of the asymmetric particle. ii. Volume diameter d v : Is the diameter of a sphere having the same volume as that of the asymmetric particle.PowerPoint Presentation: iii. Projected diameter d p : Is the diameter of the sphere having the same observed area as the particle when viewed normal to its most stable form iv. Stokes diameter d st : Is the diameter of an equivalent sphere undergoing sedimentation at the same rate as the asymmetric particle. v. volume-surface diameter d vs : Is the diameter of a sphere that has same volume to surface area ratio as the asymmetric particle.Different Equivalent Spheres: Different Equivalent SpheresPowerPoint Presentation: Frequency distribution plotParticle size distribution: Particle size distribution Most of the pharmaceutical powders are polydisperse. To describe the size of a powder Arithmetic mean, geometric mean, and harmonic mean are used. Arithmetic mean: Is defined as the sum of the particle sizes divided by the number of particles.PowerPoint Presentation: Types of arithmetic mean diameter: Where n is the number of particles with equivalent diameter, d. length mean diameter, d ln = Σ nd/ Σ n surface mean diameter, d vs = Σ nd 2 / Σ nd Volume mean diameter, d vm = Σ nd 3 / Σ nd 2 If the weight of each fraction is known, then Weight mean diameter d wm = Σ nd 4 / Σ nd 3PowerPoint Presentation: Frequency distribution curve: In this type, number or weight of particles lying within a particular size range is plotted against the mean particle size. Geometric mean: log d geo = Σ (n.logd)/ Σ nClassification Of Properties Of Powders: Classification Of Properties Of Powders Basic properties of powder can be classified into Fundamental properties :-These properties that relates to the individual particle . Derived properties :- They are dependant on fundamental properties & well defines the basic factors relating to measurements. Fundamental properties:- 1.particle size and size distribution 2.Particle shape 3.Particle volume 4.Particle number 5.Particle surface area.Different Forms of Particle Size Distribution: Different Forms of Particle Size Distribution Consider 2 populations of spherical particles of diameter 5nm and 50nm present in equal numbers. If a number distribution of these 2 particle populations is plotted, a plot consisting of 2 peaks (positioned at 5 and 50nm) of a 1 to 1 ratio would be obtained. If this number distribution was converted into volume, then the 2 peaks would change to a 1:1000 ratio (because the volume of a sphere is proportional to d 3 ). If this was further converted into an intensity distribution, a 1:1000000 ratio between the 2 peaks would be obtained (because the intensity of scattering is proportional to d 6 from Rayleigh’s approximation). In DLS, the distribution obtained from a measurement is based on intensity.Kurtious - kurtious: Kurtious - kurtious The degree of peakedness is called kurtosis. Thick tailed, sharp peaked curves are described as Leptokurtic. Thin-tailed blunt peaked curves are Platykurtic.PowerPoint Presentation: Log-normal distribution curves Here frequency is plotted against log mean particle diameter on x- axisPowerPoint Presentation: PSD OF LIPOSOMEPowerPoint Presentation: PSD OF COLLOIDAL SILICAPowerPoint Presentation: PSD OF PVC LATEXPowerPoint Presentation: PSD OF POLYSTYRENE LATEX BLEND .PowerPoint Presentation: SKEWED DISTRIBUTIONPowerPoint Presentation: FREQUENCY DISTRIBUTION DATACUMULATIVE FREQUENCY DISTRIBUTION DATA: CUMULATIVE FREQUENCY DISTRIBUTION DATA Cumulative distribution PSD may also be presented in "cumulative" form, in which the total of all sizes "retained" or "passed" by a single notional "sieve" is given for a range of sizes.PowerPoint Presentation: CUMULATIVE FREQUENCY DISTRIBUTION DATA ( UNDERSIZE ) Cumulative frequency distribution data (undersize) Point a corresponds to the median diameter. b is the lower quartile point c is the upper quartile point Powder (a) has larger range or spread of equivalent diameters than the powder (b).PowerPoint Presentation: RANGE AND CUMULATIVE DISTRIBUTIONPowerPoint Presentation: UNDERSIZE PLOTPowerPoint Presentation: PARTICLE –SIZING TECHNIQUES .The goal of all particle-sizing techniques is to provide a single number that is indicative of the particle size. .Most sizing techniques therefore assume that the material being measured is spherical and report the particle size as the diameter of the "equivalent sphere". .The way the equivalent sphere approximation works is shown for an irregularly-shaped particle. .The diameter reported for this particle will be dependent on the chosen technique .PowerPoint Presentation: 1) SEIVING: Procedure: A series of standard sieves are stacked one by above other. So that first sieves with large pore size (less sieve no)followed by decreasing the pore size(larger sieve no) ↓ A definite mass of sample is placed on the top sieve ↓ Whole the setup is shaken for definite period of time ↓ The powder remaining on each sieve after the shaking is collected. ↓ Based on sieve pore size determine the average size of particle. 10 120 s.noPowerPoint Presentation: By this particle size determine from 50µm-5000µm Seive no grade of powder 10 Coarse powder 22 Moderately coarse powder 44 Moderately fine powder 85 Fine powder 120 Very fine powderSeparation methods Powder grades according to BP : Separation methods Powder grades according to BP Description Sieve diameter m Sieve that do not allow more than 40% to pass m Coarse 1700 355 Moderate coarse 710 250 Moderate fine 355 180 Fine 180 Very fine 125PowerPoint Presentation: Sieve number Aperture size micrometer Sieve number Aperture size micrometer 10 1700 44 325 12 1400 60 250 16 1000 85 35 22 710 100 36 25 600 120 34 30 500 150 36 36 425 170 32 Designation and dimensions of I.P specifications sievesPowerPoint Presentation: This sieving method finds application in dosage form development of tablets and capsules. Advantages: It is inexpensive, simple and rapid with reproducible results. Disadvantages: a. Lower limit of the particle size is 50 μ m. b. Apertures become clogged. c. During shaking, attrition may cause size reduction of particles which leads to errors.PowerPoint Presentation: 2) OPTICAL MICROSCOPY : this can measure the particle size from 0.5microns to 100microns. It is mainly used for the not spherical particles . Procedure : A drop of suspension or emulsion is placed on the glass slide. ↓ Spread uniformly and cover with the cover slip ↓ The individual particles observed under the microscope ↓ The microscope eye piece is fitted with the micrometer by which the size of the particles are estimated.PowerPoint Presentation: This method directly gives number distribution, which can be further converted to weight distribution. Optical microscopy method is used to determine: a. Particle size analysis in suspension, aerosols . Equivalent diameters: Projected area diameter ,d a Projected perimeter, d p Feret ’s diameter d f martin’s diameter d m b . globule size distribution in emulsions .PowerPoint Presentation: C. globule size distribution in emulsions. Projected area diameter: It is a diameter of a circle with the same area as that of the particle observed to the surface on which the particles rest. Martin diameter: It is the length of the line that bisects the particle image. A line may be drawn in any direction, but must be drawn in the same direction for all the particles measured.PowerPoint Presentation: Feret diameter: It is the distance between two tangents on opposite sides of the particle parallel to some fixed directions. Advantages: Microscopy allows the observer to view the particles. Agglomeration of particles can be detected. Easy and simple . Drawbacks: Statistic relevance “tedious” if image analyse can not be used Risk for bias interpretation Difficult for high concentrations Sample preparation might be difficultPowerPoint Presentation: Calculation: The average particle size= Σ nd / Σ n Ex: 395.25/199= 1.98µm Size range µm Mean size range(d) No of particles (n) dxn Weight of the powder 0.5-1 0.75 12 9 6mg 1-1.5 1.25 24 30 11mg 1.5-2 1.75 54 94.50 48mg 2-2.5 2.25 84 189 64mg 2.5-3 2.75 17 46.75 22mg 3-3.5 3.25 8 26 12mg Σ n =199 Σ nd =395.25PowerPoint Presentation: Types of microscopes 1.Optical theory microscopes (Light microscope) 2.Electron microscopes (e.g., SEM) 3.Scanning probe microscope (SPM)PowerPoint Presentation: 1.OPTICAL MICROSCOPES . Typical magnification of a light microscope is up to 1500x with a resolution of around 200nm. .A stereo microscope is often used for lower-power magnification on large subjects. .Many wavelengths of light are used to excite fluorescence emission from objects for viewing by eye or with sensitive cameras. .New Digital microscope using optics and a camera to output a digital image to a monitor.PowerPoint Presentation: 2.Electron microscopes 1.Scanning electron microscope (SEM): looks at the surface of bulk objects by scanning the surface with a fine electron beam and measuring reflection. 2.Transmission electron microscope (TEM): passes electrons completely through the sample . This requires careful sample preparation, since electrons are scattered so strongly by most materials.Sedimentation method: Sedimentation method In this method, size is expressed as stokes diameter. Equivalent diameter: Is stokes diameter 0.001 1000 1 0.01 0.1 10 100 gravitational Centrifugal sedimentation Particle diameter(micro meters)PowerPoint Presentation: 3) Anderson pipette method: Procedure: A dilute suspension filled into the vessel upto the mark . ↓ Shake the vessel and placed in the constant temperature bath. ↓ At various intervals 10ml of the suspension is pipetted out into a dish. ↓ Dried the sample and determine the weight of the particles. ↓ find out the wt% from above weight Plot the graph wt% vs particle diameter.PowerPoint Presentation: Calculation: Where, d = diameter of the particle µ= viscosity of the medium h = height Ps = density of the particles Pl= density of the medium g = acceleration due to gravity t = time intervalPowerPoint Presentation: Benefits “Simple” and intuitive Well established Drawbacks Sensitive to temperature due to density of media Sensitive to density difference of particles Orientation of particles to maximize drag bias in the size distribution toward larger particlePowerPoint Presentation: 4) ELECTRICAL SIEVING ZONE METHOD, ( COULTER CURRENT METHOD ) It contains one beaker and tube with orifice containing the electrolyte solution. But beaker containing both electrolyte solution and the suspension of particles Beaker and tube act as the cathode and anode respectively, and connected to the amplifier. Procedure: A known volume of the suspension sucked into the tube through the orifice. ↓ Then particles enter into the tube through orifice one by one ↓ Then equal volume of the electro soln to the partticle size volume is displaced. ↓ Observe the resistance. ↓ The counter detects these changes in electrical resistance . ↓ The pulse is amplified and passed to oscilloscope(pulse height analyser ) Counts at up to 4000 particles per second are possibleParticle Size by Direct Observation: Particle Size by Direct Observation Google for ImageJSeparation methods Cascade impactores: Separation methods Cascade impactores Measure- Aerodynamic volume, Principe of operation The ability for particles to flow an air flow Size range normally 1-10 m m Benefits Clear relevance for inhalation application Can analyse content of particles Drawbacks Particles can bounce of the impactor or interact by neighbouring plates Difficult to de-aggregate particlesStream Scanning Methods Coulter counter: Stream Scanning Methods Coulter counter Measures - Volume diameter Gives number or mass average Size range - 0.1-2000 m Principe of operation Measurement on a suspension that is flowing through a tube, when a particle passes through a small hole and the presence of a particle in the hole causes change in electric resistance Benefits measure both mass and population distributions accurately Drawbacks Risk for blockage by large particles, More than one particle in sensing zone Particles need to suspended in solutionSurface area analyse Gas adsorption: Surface area analyse Gas adsorption Principe of operation Measures the adsorption of gas molecules Remove adsorbed molecules Introduce gas Measure pressure differences Range 0.01 to over 2000 m2/g. Benefits Well established High precision Gives inner pores Drawbacks Over estimation of available area Experimental difficultiesPowerPoint Presentation: LOW ANGLE LASER LIGHT SCATTERING . (LALLS) Also called as “ LASER DIFFRACTION ”. Most commonly used method of size ranging from 0.1 - 2000 microns. The angle of diffraction increases as particle size decreases, so that this Method is particularly good for measuring sizes below 1 1 micrometer. exposing the Sample to a beam of light and sensing the angular Patterns of light scattered by particles of different sizes.PowerPoint Presentation: In this , particle size distributions are calculated by comparing a sample’s scattering pattern with an optical model . Two different models are used: 1.MIE THEORY & 2.FRAUNHOFER DIFFRACTION THEOY. 1.MIE THEORY In this the particles are considered to be finite objects instead of point scatterers. Scattering occurs with particles much smaller than the wavelength of the light ( d = 0.05 < d < lambda ) is termed as “ RAYLEIGH SCATTERING “. Scattering from particles with diameters near the wavelength of the light ( 0.05 lambda < d < lambda ) is termed as “DEBYE SCATTERING”.2.FRAUNHOFER DIFFRACTION THEORY: 2.FRAUNHOFER DIFFRACTION THEORY This model treats particles as opaque, circular apertures obstructing the beam of light. The particle behaves like a circular aperture, and its scattering pattern is called as AIRY PATTERN. Mie scattering occurs for particles with diameters larger than the wave length of the incident light. It was to be more accurate over a wider range of sizes , particularly for particles less than 50 microns in size.PowerPoint Presentation: PREDICTION OF SCATTERED LIGHT FRAUNHOFER VS MIE THEORY. Older instruments used the less accurate fraunhofer method ,this was due to limited computer processing power. Mie theory correctly predicts the scattering at all wavelengths of light at all angles. unlike fraunhofer, Mie theory: Accounts for the spherical particles are present. Is valid for all wavelengths , scattering angles and sizes of particle. It correctly predicts scattering intensities and also correctly predicts the secondary scattering.PowerPoint Presentation: TWO TYPES OF LIGHT SCATTERING Static light scattering ( also called Mie scattering ) and Dynamic light scattering ( also called photon correlation spectroscopy or quasi-elastic light scattering). static light scattering measures scattered intensity as a function of angle like xrd) while Dynamic light scattering measure variation in time of scattered intensity at a fixed scattering anglePowerPoint Presentation: PRINCIPLE OF DLS Emulsions and molecules in suspension undergo Brownian motion. If the particles or molecules are illuminated with a laser , the intensity of the scattered light fluctuates at a rate that is dependent upon the size of the particles. Analysis of these intensity fluctuations yields the velocity of the Brownian motion and hence the particle size using Stokes - Einstein relationship .PowerPoint Presentation: The zetasizer measures the size of the particles in fluid down to less than a nanometer by observing the Brownian motion of the particle. Submicron particle sizes are measured by observing the scattering of laser light from these particles , determining the diffusion speed and deriving the size from this using Stoke 's - Einstein relationship. Actually we are measuring diffusion coefficient .PowerPoint Presentation: In DLS the larger particles scatter more light than small particles ,then the DLS is very sensitive to the presence of aggregates. Hence this technique is an excellent basis for studying the stability of submicron particle dispersions.PowerPoint Presentation: ACOUSTIC SPECTROSCOPY Instead of light , this method employs ultrasound for collecting information on the particles that are dispersed in fluid. Alternative term is ultrasound attenuation spectroscopy. Dispersed particles absorb and scatter ultra sound similar to light. Instead of measuring scattered energy versus angle , as in case of ultrasound , measuring of transmitted energy versus frequency is a better choice.PowerPoint Presentation: In DLS , one measures the time dependence of the light scattered from a very small region of solution, over a time range from microsecond to mille second. These fluctuations in the intensity of the scattered light are related to the rate of diffusion of molecules in Brownian motion. The data can be analysed to directly give the diffusion coefficients of the particles doing the scattering.PowerPoint Presentation: Derived properties of powder :- DENSITY OF POWDERS (a) BULK DENSITY (b)TAPPERED DENSITY (c) GRANULAR DENSITY (d)TRUE DENSITY FLOW PROPERTIES OF POWDERS ANGLE OF REPOSE COMPRESSIBILITY INDEX HAUSNER RATIO POROSITY BULKINESS 80Introduction : Introduction When we concerned with the flow of any material it relates with Rheology. Deformation of the body is the relative displacement of its mass points without moving the centre of gravity. But in fact that powers are difficult to discussing in rheological term. Hence we can able to define the bulk flow properties of the power in terms of fundamental measurable characteristics of particle of them. 81PowerPoint Presentation: 1. DENSITIES OF PARTICLES : TYPES OF DENSITIES: A – TRUE DENSITY The true density , or absolute density, of a sample excludes the volume of the pores and voids within the sample. -B – BULK DENSITY (W/V) - The bulk density of a sample value includes the volume of all of the pores within the sample.PowerPoint Presentation: DENSITIES OF THE PARTICLES During tapping , particles gradually pack more efficiently, the powder volume decreases and the tapped density increases.PowerPoint Presentation: volumes Definitions True volume Volume of powder itself Granule volume Volume of powder + voids (inter particle spaces ) Bulk volume Volume of powder + volume of intra particle space+ voids Void volume Bulk volume – true volume (Vb - Vp)Density Of Particle : Density Of Particle Three types of densities Universally defined as weight per unit volume. True density:- it is the weight of material it self Granule density:- Measured by mercury displacement method. Mercury fills the voids, but fails to penetrate internal particles. as it has non weighting properties. Granule volume related to weight of the mercury that displaced by granules in pycnometer. Granule density = granule weight granule volume 86PowerPoint Presentation: Bulk density:- Bulk density = mass of the powder (w) bulk volume (Vb) When particle are loosely packed , lots of gaps in between particle. Bulk volume increases making powder light. Powder classified as ‘light’ or ‘heavy’ “light powder have high bulk volume” ‘Bulk density apparatus’ is used to determine bulk volume. applications:- Used to check uniformity of bulk chemicals. Size of capsule determine by bulk volume. Higher the bulk volume bigger the size of capsule. 87PowerPoint Presentation: True density measurements- For non porous solid:- True density & granule density identical. Both obtained by- Helium displacement method Liquid displacement method For porous material (having an internal surface) Using helium densitometer 88PowerPoint Presentation: Arrangement of helium pycnometer Bulk density apparatus Sample holder Variable volume piston Pressure detector valve atoms vacuum Helium 89PowerPoint Presentation: FLOW PROPERTIES OF POWDERAngle Of Repose: THE ANGLE OF REPOSE : frictional forces in a loose powder can be measured by the angle of repose. = the maximum angle possible between the surface of a pile of powder and horizontal plane = coefficient of friction u between the particles: tan Ɵ = h/r r = d/2 Angle Of ReposePowerPoint Presentation: Angle of repose(Ɵ ) Type of flow <25 EXCELLENT 25 - 30 VERY GOOD 30 - 35 GOOD 35 - 40 SATISFACTORY 40 - 45 POOR >45 VERY POOR The rougher and more irregular the surface of the particles ,the higher will be the angle of repose.PowerPoint Presentation: Effect on angle of repose of various procedure decrease particle size- higher angle of repose Fines (up to 15%)-increase angle of repose Lubricants at low concentration- ↓ angle of repose Rough & irregular surface- higher angle of repose Lower the angle of repose- better the flow property Angle of repose apparatus. 93PowerPoint Presentation: Tests to evaluate the flow ability of a powder : Carr's compressibility index A volume of powder is filled into a graduated glass cylinder and repeatedly tapped for a known duration. The volume of powder after tapping is measured. Carr's index (%) = ((Tapped density - Poured or bulk density) x 100)/Tapped density Bulk density = weight/bulk volume Tapped density = weight/true volumePowerPoint Presentation: % COMPRESSIBILITY FLOW PROPERTY < 10 EXCELLENT FLOW 10 - 12 VERY GOOD 12 - 15 GOOD FLOW 15 – 20 SATISFACTORY 20 - 30 POOR > 30 VERY POOR LESS THE PERCENTAGE OF FINES , LESS WILL BE THE DIFFERENCE IN TAPPERED DENSITY AND BULK DENSITY.Hauser′s Ratio: Hauser ratio : Hauser ratio = Tapped density/Poured or bulk density Hauser ratio was related to interparticle friction: **Value less than 1.25 indicates good flow (=20% Carr). The powder with low interparticle friction, such as coarse spheres. **Value greater than 1.5 indicates poor flow (=33% Carr). more cohesive, less free-flowing powders such as flakes. **Between 1.25 and 1.5,added glidant normally improves flow. **> 1.5 added glidant doesn't improve flow. Hauser′s RatioPacking Arrangement: Packing Arrangement Two ideal packing materials Closest or rhombohydral Most open, loosest or cubic packing. Cubic arrangement Closest or rhombohydral 97PowerPoint Presentation: Theoretical porosity of powder consist of uniform sphere in Closest packing- 26% Loosest packing- 48% Real powder have porosity in between 30 to 50%. In suspension, porosity may above the theoretical max limit 48%. Crystalline materials porosity- <1 % (under force 10000 lb/in 2 ) 98PowerPoint Presentation: DERIEVED PROPERTIES OF POWDERS 5.POROSITY Suppose a non porous powder is placed in a graduated cylinder: The total volume occupied is known as the bulk volume v b. BULK VOLUME= TRUE VOLUME + VOLUME OF SPACES BETWEEN PARTICLES. The volume of the spaces, the void volume , V = V b - V p . V P is the true volume of particles. Porosity or voids is determined as the ratio of void volume to bulk volume. POROSITY = ε = V b – V p / V b = 1 – V p V b POROSITY IS THE EXPRESSED IN PERCENT , ε X 100.Shapes of Pores: Shapes of Pores Conical Interstices Slits Cylindrical Spherical or Ink Bottle Pore Shapes F. Rouquerol , J. Rouquerol, K. S. W. Sing, Adsorption by Powders and Porous Solids, Academic Press, 1-25, 1999Size of Pores (IUPAC Standard): Size of Pores (IUPAC Standard) 2 nm 50 nm Micropores Mesopores Macropores Zeolite, Activated carbon, Metal organic framework Mesoporous silica, Activated carbon Sintered metals and ceramics Porous material are classified according to the size of pores: material with pores less than 2 nm are called micropores, materials with pores between 2 and 50 nm are called mesopores, and material with pores greater than 50 nm are macrosporesMethods for Calculation of Pore Size Distribution: Methods for Calculation of Pore Size Distribution BJH (Barrett, Joyner and Halenda) method DH (Dollimore Heal) method Dubinin-Astakhov method HK (Horvath-Kawazoe) method Saito-Foley method Mesoporous solids Microporous solids NLDFT (Non Local Density Functional Theory) and Monte Carlo simulation method Microporous and Mesoporous solidsPorosity Analyzer: Porosity Analyzer Outgassing station Analysis station Liquid nitrogen bathPowerPoint Presentation: A sample of calcium oxide powder with a true density of 3.203 and weighing 131.3g was found to have a bulk volume of 82 cm 3 when placed in a 100ml graduated cylinder . calculate the porosity? THE VOLUME OF THE PARTICLE IS 131.3g / (3.203 g/cm 3) =41 cm 3. ε= v b – v p = 82-41 v b 82 ε = 0.5 or 50 %. SOLUTIONPowerPoint Presentation: 6. BULKINESS = SPECIFIC BULK VOLUME = RECIPROCAL OF BULK DENSITY It is an important consideration in the packaging of powders. The bulk density of calcium carbonate vary from 0.1 to 1.3 and the lightest (bulkiest) type require a container about 13 times larger than that needed for the heaviest variety. (BULKINESS INCREASE WITH A DECREASE IN PARTICLE SIZE.) In mixture of materials of different sizes, the smaller particles sift between the larger ones and tend to reduce bulkiness .Moisture content: Moisture content Higher the moisture content greater the cohesion & adhesion. Flow properties can be improved by following methods- Powder processes into granules to improve flow. Choosing optimum size of granules (400 to 800 um) Incorporating optimum amount of fines (about 15%) Incorporating optimum concentration of lubricants ( magnesium stearate ,talc) 107Nature Of Particle: Nature Of Particle Nature of particle Effect on flow property Smooth surface Increase the flow property Rough surface Poor flow due to friction Flat and elongated particle Gives high porosity high density & low porosity Good flow property 108Dispersability: Dispersability It is the ability of a material to flow or pour easily over a planes. Dispersability, dustiness, & floodability are inter- related term . weight of powder in watch glass Dispersability (%) = ˣ 100 initial weight of the sample Dispersibility apparatus:- A hallow cylinder through which is Drop from a height 61 cm above the glass watch. 109PowerPoint Presentation: Any loss of the powder during the fall is the result of dispersion calculated using the above relation. Lycopodium spores shows the greatest dispersibility and it is assigned as 100 % dustability. Dustability : - Talcum powder----------- 57 % Potato starch---------------27% charcoal --------------------23%PowerPoint Presentation: POWDER FLOW PROBLEMS: FLOW PROPERTIES: Powders may be free – flowing or cohesive ( sticky) Many common manufacturing problems are attributed to powder flow: Powder transfer through large equipment such as hopper. Uneven powder flow excess entrapped air within powders Capping or lamination . 3.Uneven powder flow increases particle ‘s friction with die wall causing lubrication problems , and increase dust contamination risks during powder transfer.Compression Properties: Compression Properties This property normally used for the preparation of the tablet . This process also called compaction. During this porosity of powder changes. Plastic behaviour:- Deformed on compression Compact powder get deformed which is tapped into close packing. For e.g. kaolin which have soft & spongy particle Dilatant behaviour:- Shows unexpected expansion under the stress. Some substances when compacted exhibits higher porosity than the powder in close packing. 114PowerPoint Presentation: For e.g. sodium chloride. Compression properties of most drugs extremely poor. Hence compression vehicle is added such as- Lactose Calcium phosphate Microcrystalline cellulose Low dose drug tablet prepared by direct compression But high dose drug prepared by granulation methods. Tablet material should be plastic i.e. undergoing permanent deformation 115PowerPoint Presentation: FACTORS AFFECTING THE FLOW PROPERTIES OF POWDERSPowerPoint Presentation: Alteration of Particle's size & Distribution . There is certain particle size at which powder's flow ability is optimum. .Coarse particles are more preferred than fine ones as they are less cohesive. .The size distribution can also be altered to improve flow ability by removing a proportion of the fine particle fraction or by increasing the proportion of coarser particles, such as occurs in granulation .PowerPoint Presentation: Alteration of Particle Shape & texture Particle's Shape: Generally, more spherical particles have better flow properties than more irregular particles. Spherical particles are obtained by spray drying ,or by temperature cycling crystallization. Particle's texture : particles with very rough surfaces will be more cohesive and have a greater tendency to interlock than smooth surfaced particles.PowerPoint Presentation: Alteration of Surface Forces - Reduction of electrostatic charges can improve powder flow ability. Electrostatic charges can be reduced by altering process conditions to reduce frictional contacts . - Moisture content of particle greatly affects powder's flow ability. -Adsorbed surface moisture films tend to increase bulk density and reduce porosity . -Drying the particles will reduce the cohesiveness and improve the flow. -Hygroscopic powders, stored and processed under low humidity conditions .PowerPoint Presentation: Formulation additives (Flow activators) -Flow activators are commonly referred as glidants. -Flow activators improve the flow ability of powders by reducing adhesion and cohesion . e.g. talc , maize starch and magnesium stearateFactors influenced by particle size: Factors influenced by particle size Surface area : increased S.A. affects the therapeutic efficiency of medicinal compounds that possess a low solubility in body fluids by increasing the area of contact between the solid and the dissolving fluid. Thus compound dissolves in a shorter time. Extraction : the time required for extraction is shortened by the increased area of contact between the solvent and solid and the reduced distance the solvent has to penetrate the material. Dissolution : the time required for dissolution of solid chemicals is shortened by the use of smaller particles.PowerPoint Presentation: Drying : the drying of wet mass may be facilitated by milling, which increase the S.A. and reduces the distance the moisture must travel with in the particle to reach the outer surface. Mixing : the mixing of several solid ingredients of a pharmaceutical is easier and more uniform if the ingredients are approximately the same and small size . Lubrication : lubricant used in compressed tablets and capsules function by virtue of their ability to coat the surface of granulation or powder.Particle size and the lifetime of a drug: Particle size and the lifetime of a drug In production : particle size influences the production of formulated medicines as solid dosage form both tablets and capsules are produced Powders with different particle size have different flow and packing properties , which alter the volume of powder during each encapsulation or table compression event . In Body: after administration of the medicine, the dosage should release the drug in to solution at optimum rate . This depends on several factors, one of which will be particle size of drug. Particles having small dimension will tend to increase the rate of solutionPowerPoint Presentation: RELATIONS 1.PARTICLE SIZE INDIRECTLY PROPOTIONAL TO : SURFACE AREA ., ABSORPTION , BIOAVALABILITY , SURFACE FREE ENERGY SURFACE TENSION FRICTIONAL FORCES AMOUNT OF ADSORBATE ADSORRBED DENSITY 2.PARTICLE SIZE IS DIRECTLY PROPORTIONAL TO: DOSE ADMINISTERED , FLOW PROPERTY .Conclusion: Conclusion As the particle size and powder properties ultimately effects the drug release from the dosage form, importance should given to it while designing the dosage form for the good release of the drug and to avoid side effects. Particle size is an important parameter both for the production of medicines containing particulate solids and in the efficacy of the medicine administration.PowerPoint Presentation: References: Physical pharmacy and pharmaceutical sciences by Martin fifth edition, 533 to 544. Pharmaceutics by M.E Aulton second edition 153 to 165. Text book of physical pharmaceutics by C.V.S. Subrahmanyam 181 to 206. Instrumental Analysis by skoog. Heller. Crouch 1038 to 1051 . You do not have the permission to view this presentation. In order to view it, please contact the author of the presentation.