Micromeritics - Fundamental and Derived Properties of Powders

Definition
Advantages
Disadvantages
Fundamental Properties
1. Particle Size
2. Particle Shape
3. Particle Surface Area
4. Particle Weight
5. Particle Number
Derived Properties
1. Densities
2. Bulk Properties
3. Porosity
4. Bulkiness
Methods of Determination of Fundamental Properties.
Methods of Determination of Flow Properties.

1. M I C R OMER I T IC S Ms. Chitralekha G. Therkar Assistant Professor Dept. of Pharmaceutics Siddhivinayak College of Pharmacy, Warora

2. Definition: It is the science and technology of small particles i.e. powdered particles and it also deals with the fundamental and derived properties of the powders . The unit of particle size is expressed in micrometer (μm) , micron ( μ ) and it is equal to 10 -6 m . Generally, the size of larger particles can be expressed in terms of millimetres (mm) and the size of smaller particles can be expressed in terms of nanometres (nm). Various units used to express the size of particles are, Millimeter - 10 -3 Micrometer - 10 -6 Nanometer - 10 -9 Angstrom - 10 -10 Picometer - 10 -12 A s particle size decreases, the surface area increases . The knowledge and control of particle size is important in pharmacy and material science. Introduction

3. applications To determine the Particle size To determine the distribution of particles. To determine the effective particle size for any novel preparation. In clinical research. In research, formulation and development. The particle size and surface area of any particle can be related to the physio - chemical and pharmacological properties of the drugs to be incorporated in the formulation as follows, Release and Dissolution - Particle size and surface area influence the release of a drug from a dosage form. Higher surface area allows intimate contact of the drug with the dissolution fluids and increases the drug solubility and dissolution. Absorption and Drug action - Particle size influence the drug absorption and subsequently the therapeutic action. Higher the dissolution, faster the absorption and hence quicker and greater the drug action.

4. Physical Stability - The particle size and the surface area in any formulation influences the physical stability of the suspensions and emulsions. Smaller the size of particle, better the physical stability of the dosage form. Dose uniformity - Good flow properties of granules and powders are important in the manufacturing of tablets and capsules. Particle size range of different systems SN Formulations Size range 1 Suspensions and Emulsions 0.5 μ m to 10 μ m 2 Flocculated suspension and coarse emulsion 10 μ m to 50 μ m 3 Fine particles 150 μ m to 1 mm 4 Granules 1 mm to 3.5 mm

5. P ar t i c l e S i z e a n d Particle S i z e Distribution In a collection of particles of more than one size , two properties are important , The shape and the surface are a of the individual particle. The particle size and distributions ( Size range and number or weight of particle ) The calculations are done visualizing an imaginary sphere and size of a sphere is readily expressed in terms of its diameter as follows, The surface diameter (d s ) is the diameter of a sphere having the same surface area as the particle. The volume diameter (d v ) is the diameter of a sphere having the same volume as the particle. The projected diameter (d p ) is the diameter of a sphere having the same area as the particle. The stokes diameter (d st ) is the diameter which describes an equivalent sphere undergoing sedimentation at the same rate as the asymmetric particle .

6. Particle Size Distribution Any collection of particles is usually polydisperse . Therefore it is very necessary to know not only the size of a certain particles, but also how many particles of the same size exist in the sample. Thus, we need an estimate of the size range present and the number or weight fraction of each particle size. It represents the particle size distribution and from it we can calculate an average particle size for the sample. When the number or weight of particles lying within a certain size range is plotted against the size range , a frequency distribution curve is obtained. It is important to estimate the particle size distribution because it is possible for many formulations to have two samples with same average diameter but different distributions .

7. Mean Particle Size Particle size is measured by mean, median and mode. Mean is the average particle size. This means are of three different types namely, arithmetic, geometric and harmonic. Arithmetic mean is the sum of particle size divided by number of particles. The particles observed under microscope are classified into each size range to know no. of particles in each size range as follows, Size Range Mean No. of particles n x d 10 – 20 15 32 480 20 – 30 25 41 1025 30 – 40 35 63 2205 40 – 50 45 85 3825 50 – 60 55 52 2860 60 – 70 65 21 1365 70 – 80 75 06 450

8. Determination of p article s ize and particle s ize d istribution is done by following methods, 1. Optical Microscopy Light microscopy Scanning Electron Microscopy Transmission Electron Microscopy 2. Sieving 3. Sedimentation Andreasen Pipette Method Centrifugal Sedimentation Method 4. Particle volume measurement (Coulter Counter Method) Methods

9. 1. Optical Microscopy For particle size in range of 0.2 to 100 micrometer the size is expressed as projected diameter , which describes the diameter of a sphere having the same area as that of asymmetric particle when observed under microscope. For good size distribution atleast 300-500 particles must be observed. Methodology - Prepare a powdered suspension whose size to be determined using a vehicle in which it is insoluble. If it is slightly soluble then the saturated solution of powder can be used. A suspension drop is mounted on the slide and it is observed under the microscope and the eyepiece of microscope is fitted with the micrometer from which the particle size is estimated. All particles observed in a field are counted through an eyepiece. For ease in counting, the field can be projected on a screen or photographed or can be counted with electronic scanners (Scanning Electron Microscopy)

10. Advantages Easy and simple. It allows observer to view the particles particularly . Agglomeration and any contamination in powder can be detected. Particles in the dispersion must be free from motion which can be achieved using coverslip. Disadvantages Measured diameter represents only two dimensions i.e. length and breadth , the depth is not obtained. Method is slow and tedious. Large sample is required . Advantages and Disadvantages

11. 2. S IE V I NG method For particles in the size range of 50 - 1500 μ m are expressed as sieve diameter which can be describes as the diameter of a sphere that passes through the same sieve aperture as the asymmetric particle . Sieves for pharmaceutical testing are constructed from wire d cloth with square meshes, woven from wire of brass, bronze or stainless steel and should not be coated or plated because t here must be no reaction between material of sieve and the substance to be sieved. Methodology - Sieves are arrange in a nest, stacked over one another with coarse at the top and powdered sample is placed on the top of the sieve. Sieve set is fixed to mechanical shaker and powder is shaken for a certain period of time (20 mins) and the powder retained on each sieve is weighed . And percent powder retained o each sieve is calculated. Note – This method gives the weight size distribution and the type of motion influences sieving is vibratory motion followed by side tap motion and rotary motion.

12. Advantages Inexpensive Simple method Rapid with reproducible results. Disadvantages Lower limit is 50 μ m , since it is limited by smallest size of sieve. Moisture can lead s to aggregation, leading to clogging and improper results after procedure. During shaking attrition leads to size reduction. Advantages and Disadvantages

13. 3. SEDIMENTATION method This method is u se for the particles of size range of 1 to 200 μ m and the particle size is expressed as s toke’s diameter which describes the diameter of equivalent sphere having same rate of sedimentation as that of asymmetric particle . It utilizes the apparatus known as Andreasen's pipette . Methodology - It consists of 550 ml stoppered cylindrical vessel with about 5.5 cm of internal diameter with a vertical scale graduated from 0 to 20 cm on it. There are 3 basic parts, Stopper has an integral 10 ml bulb pipette fitted with a 2 way stopcock and side tube for discharging sample. Stem of pipette made of narrow bore tuning in order to minimize the volume retained in the stem after each sampling. Pipette is so fitted in the cylinder such that its lower tip is 20 cm below the surface of the suspension.

14. Andreason’s Pipette

15. Methodology Transfer the sample up to the mark . Vessel is stoppered and shaken to distribute particles uniformly. Stopper is removed and two way pipette is placed and whole assembly is kept undisturbed in constant temperature water bath. At different time intervals the 10 ml samples are withdrawn using 2 way stopcock and collected in previously weighed china dish. Sample are evaporated and weighed and are referred to as weight undersize. These weights are converted into cumulative weight s. Graph is drawn from data to get the curve of distribution.

16. 4. Particle Volume Measurement The coulter counter method is generally used to determine the particle volume distribution. Principle - When a particle suspended in a conducting liquid passes through a small orifice on either side of which are electrodes a change in electrical resistance occurs. Instrumentation It consists of two electrodes one of which is dipped into a beaker containing dilute suspension in an electrolyte (such as 0.9% NaCl). The other electrode is dipped into the electrolyte solution contained in a glass tube which is immersed into the beaker containing the particle suspension in the electrolyte. The glass tube has a very small orifice at its lower end through which the particles are sucked into the inner glass tubes.

17. W O RKING Methodology A known volume of suspension is pumped through an orifice so that only one particle passes at a time through an orifice and a constant voltage is applied across electrodes so as to produce a current. As the particle travels through orifice, it displaces its own volume of electrolyte and this results in an increased resistance between the 2 electrodes and this is proportional to volume of the particle. This change in electrical resistance is termed as voltage pulse which is related to particle volume . Voltage pulse is amplified and fed to a pulse height analyzer. The pulse height is directly proportional to particle volume. The analyzer is previously calibrated in terms of a particle size for different threshold settings. For a given threshold value pulses are electronically counted. By changing the threshold settings gradually number of particles of each size range is obtained and thus particle size distribution can be obtained .

18. Advantages Operation is very rapid with a single count taking less than 30 sec. Since large n umber of particles are counted results are more reliable. Instrument can operate with particles between 0.5 and 1000 micrometer. Since aperture is automatic the operator variability is avoided. Disadvantages Material has to be suspended in electrolyte liquid before the measurement. Aggregation of particles can give false results. Advantages and Disadvantages

19. Specific Surface The specific surface is the surface area per unit volume or per unit weight. By taking the general case fort he asymmetric particles where characteristic dimension is not defined, the surface area per unit volume is given as, S v = S v = S v = Where, n is the no. of particles. d is the diameter of particle. is volume factor. is surface area factor.  

20. Surface Area Determination The surface area can be determined by two methods , 1. Adsorption Method A d s o r p t i o n o f s o l u t e o n p ow d e r A d s o r p t i o n o f g a s o n p ow d e r 2. A i r P e r m e a b i li ty M e thod

21. Adsorption Method Particles with the large specific surface are good adsorbents for the adsorption of gases and solutes from solution. The amount of gas or solute adsorbed on the sample of powder to form a monolayer is found out from this data and the surface area of powder is determined. Adsorption of solute on powder Solution of a suitable solute is first prepared in a medium in which the adsorbent powder is insoluble. Eg, Stearic acid in ethanol. Known amount of powder is then added to the solution and contents are stirred for sufficient period of time. After equilibrium is attained the powder is filtered and amount of solute remaining in solution is determined by suitable method. Difference between quantity added and the remaining quantity in solution gives the quantity that adsorbed and then value obtained amount adsorbed per gram of powder is calculated.

22. 2. Adsorption of Gas on Powder Instrument to be used for this process is called as Quantasorb. Methodology - Powder whose surface area is to be determined is introduced into the cell of instrument. The adsorbate gas i.e. nitrogen and helium which is an inert gas and not adsorbed are passed through powder in cell. Thermal conductivity detector measures amount of nitrogen gas adsorbed at every equilibrium pressure. Bell shaped curve is obtained on strip chart recorder. Volume of nitrogen gas V m adsorbed by 1 gm of powder when the monolayer is formed is given by BET equation = Where, V = volume of gas in cm 3 adsorbed per gram of powder . V m = volume of nitrogen gas adsorbed in monolayer. P = vapour pressure of liquified nitrogen at saturation. b = constant P = pressure.

23. AIR PERMEABILITY METHOD Principle R esistance offered to the flow of a fluid such as air through a plug of compacted powder is proportional to the surface area of a powder . i.e. greater the surface area per g r am of the powder greater is the resistance to flow. Surface area by air permeability is generally carried out with instrument called Fisher Subsieve Sizer . Powder is packed in the sample holder as a compact plug. In this packing surface, contacts appear as a series of capillaries. The surface of capillaries is a function of surface area of powders.

24. W here , A = cross sectional area of a bed ∆P= pressure difference of plug T= time of flow in seconds L= length of sample holder ε= porosity of powder S w = s u r f a c e a r e a p e r g r a m o f p ow d e r η= viscosity of air K = c o n s t an t ( 5 + . 5 ) V= volume of air flowing through bed Kozeny carman equation is used to estimate the surface area,

25. Instrumentation Instrument is known as Fisher Subsieve Sizer . It is consist of the sample tube which contain s packed powder sample with 2 ends . One end is connected to air pump through constant pressure regulator and other end is connected to manometer containing a suitable liquid.

26. W o r k i n g Air pump builds up air pressure and is connected to a constant pressure regulator. A i r i s p a s s e d t h r o u g h a d r y e r t o r e m o v e a n y moisture and t h e n a l l o w e d t o f l o w t h r o ug h t h e p a c k e d powder. The flow of air is measured using manometer. Level of f l u i d i n m a n om ete r i nd i c a te s a v e r a g e d i a m e t e r o f t h e p a r t i c l e s w h i c h c a n b e r e a d f ro m calculator charts supplied with equipment.

27. Particle Shape The shape affects the flow and packing properties of a powder as well as have some influence on the surface area. S urface area per unit weight is an important characteristic of a powder when undertaking surface adsorption and dissolution rate studies. A sphere has minimum surface area per unit volume. The more asymmetric a particle, greater is the surface area per unit volume. A spherical particle is characterized completely by its diameter. As the particle becomes more asymmetric, it becomes increasingly difficult to assign a meaningful diameter to the particle. Surface area of spherical particle = π d s 2 Volume of spherical particle = 1/6 π d s 3 Where, d s is surface diameter of spherical particle.

28. Fig. - Various shapes of particles.

29. Determination of particle shape Microscopy Method Light scattering method

30. 1. Porosity - Suppose a nonporous powder, is placed in a graduated cylinder: the total volume occupied is known as the bulk volume V b . bul k v olu m e = t ru e v olu m e + v olu m e o f s p ac e s b etw een particles . The volume of the spaces, the void volume, V = Vb - Vp Vp is t he t ru e v olu m e of par t i c le s . The porosity or voids ε of powder is determined as the ratio of void volume to bulk volume. Derived properties of powders

31. 2- Densities of particles: - Density is defined as weight per unit volume (W/V). 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 value includes the volume of all of the pores within the sample.

32. Densities of particles During tapping, particles gradually pack more efficiently, the powder volume decreases and the tapped density increases.

33. Derived properties of powders (Cont.): 3- Bulkiness = Specific bulk volume = reciprocal of bulk density: I t is an i m por t ant c on s idera t ion in t he pa ck aging of po w der s . 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. (Bul k ine s s in c rea s es w i t h a de c rea s e in par t i c le s i z e). In mixture of materials of different sizes, the smaller particles sift between the larger ones and tend to reduce bulkiness.

34. True Density It is the density of actual solid material devoid of inter and intraparticle spaces or voids and is defined as the ratio of the given mass of p ow d e r an d i t s t r u e v o l u me . I t c a n b e d e t e r m i n e d b y two m e th o ds Liquid displacement method Gas or Helium Displacement method

35. Liquid Displacement Method It is used for non porous powders. Select the solvent in which powder is insoluble. Normally water and ethyl alcohol are used. W t o f p y c n o m e t er = m 1 W e i ght o f p y c n o m e t er + p ow d er = m 2 Weight of sample = m2-m1 Weight of pycnometer + sample + water = m3 W e i ght o f p y c n o m e t er + w a t er = m 4 Weight of water displaced by powder = m4-m3 True Density of Powder = weight of material volume of water displaced by powder

36. Gas or Helium Displacement Method H e li u m p e n e t r a t es t h e sm all e s t p o r es a n d c e r v i c e s . It g i v es a very closer value to its true density. Construction: It consists of sample holder(A) which is sealed after introducing the sample. Valve (B) is connected to the sample holder. It has provisions for removal of air and introduction of helium gas(since it does not adsorb on the solid sample. Pressure detector (C) is induced in order to maintain preset constant pressure. Piston (D) is attached to read the corresponding pressure which is also related to volume of powder

37. Working: Initially volume of empty pycnometer is determined Air is removed from sample holder by applying vaccum Helium is passed through valve B Pressure is set at a particular value with a piston D At this position the reading on scale denotes U1 which is the vol of empty cell

38. In next step pycnometer is caliberated by placing a standard sample(stainless steel spheres) of known true volume in the sample holder Sample holder is sealed and air is removed Same amount of helium gas is introduced Pressure is adjusted to preset value by piston At this stage scale reading is denoted by U2 Difference between U1 and U2 gives the volume occupied by spheres

39. Stainless steel spheres are now replaced by test sample powder of known volume(V c ). Air is replaced by helium gas. Pressure is adjusted with the help of a piston. At this stgae piston reading is denoted as U s . Difference between U 1 and U s gives volume occupied by sample. • Where Vt is true volume of sample

40. Tests to evaluate the flowability of a powder: 1- 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 (%) = T a pp e d d e n s i t y - P o u r e d o r bul k d e n s i t y x 100 Tapped density B ul k d e n s i t y = w ei gh t / bul k v o lu me Tapped density = weight / true volume

41. Carr’s compressibility index (Cont.): Relationship between powder flowability and % compressibility Flow description % compressibility Excellent flow 5 - 15 Good 16 - 18 Fair 19 - 21 Poor 22 - 35 Very poor 36 - 40 Extremely poor > 40

42. Tests to evaluate the flowability of a powder (Cont.): 2- Hausner ratio: Tapped density Hausner ratio = P o u r e d o r bul k d e n s i t y H a u s n er ra t i o w as re l a t ed t o i nt er p ar t i c l e f r i c t i on : **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. ** B e t w ee n 1 . 2 5 a n d 1 . 5 , a dd e d gl i d a n t n o rm a ll y i m p r o v e s f l o w . ** > 1.5 added glidant doesn’t improve flow.

43. Tests to evaluate the flowability of a powder (Cont.): c a n b e 3- The angle of repose φ: T h e f r icti o n a l f o r c e s in a l o o se po w d e r measured by the angle of repose φ. φ = t h e m a x i m u m a n g l e po ss i b l e be tw ee n t h e s u r f a ce of a pile of powder and horizontal plane = coefficient of friction μ between the particles: t a n φ = μ t a n φ = h / r r = d / 2

44. 3- The angle of repose φ (Cont.): The sample is poured onto a horizontal surface and the angle of the re s ult i n g p y ra m i d i s m ea s u re d . The user normally selects the funnel orifice through which the powder flows slowly and reasonably constantly. Angle of repose less than 20 (excellent flow) Angle of repose between 20-30 (good flow) Angle of repose between 30-34 (Pass flow) Angle of repose greater than 40 (poor flow) ***The rougher and more irregular the surface of the particles, t h e high er w il l b e t h e a ngl e o f r e po se.

45. Factors affecting the flow properties of powders: Improvement of P o w d e r Flowability Particle’s size & Di s t r i b u t i o n P a r t i c l e Shape & texture Su r f a c e forces Flow Activators

46. Factors affecting the flow properties of powders (Cont.): 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 flowability by removing a proportion of the fine particle fraction or by increasing the proportion of coarser particles, such as occurs in granulation.

47. Factors affecting the flow properties of powders (Cont.): 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.

48. Factors affecting the flow properties of powders (Cont.): Formulation additives ( Flow activators) Flow activators are commonly referred as glidants. Flow activators improve the flowability of powders by reducing adhesion and cohesion. e.g. talc, maize starch and magnesium stearate

49. Thank You