Micromeritics

Basics about micromeritics

1. ASSIGNMENT ON MICROMERITIC PROPERTIES OF POWDERS AND GRANULATION Presented by Suraj Parashuram Bhange

2. Contents Introduction to Micromeritics Particle s ize distribution Methods to determine particle size Derived properties of powder Factors affecting flow properties of powder Application of micromeritics Case study and the protocol

3. Micromeritics Definition: It is the science and technology of small particles. Control of the size and the size range of particles are significant importance in pharmacy because the size and surface area of the particles related to the physical, chemical and pharmacological properties of drug. The unit of particle size used in the micrometer ( μ m), micron ( μ ) and equal to 10⁻⁶ m. As particle size decreases, area increases.

4. Particle Size in Pharmaceutical Dispersions: Sr. No. Particle Size Examples 1. 0.5-10 μ m Suspension and Fine Emulsion 2. 10-50 μ m Coarse Emulsion Particles, Flocculated Suspension 3. 50-100 μ m Fine Powder Materials 4. 150-1000 μ m Coarse Powder Range 5. 1000-3360 μ m Granules

5. Particle size Distribution When the number or weight of particles lying within a certain size range is plotted against the size range or mean particle size the frequency distribution curve is obtained. This is important because it is possible to have two samples with the same average diameter but different distributions.

6. Fig.1.Frequency Distribution Curve

7. Methods to determine particle size Optical Microscopy Sieving/ Sieve Analysis Sedimentation Particle Volume measurement

8. 1. Optical Microscopy According to optical microscopic method, an emulsion or suspension, diluted or undiluted is placed on the slide which is then mounted on a mechanical stage. The eye piece has a micrometer scale by which the particle size can be measured. This method is used for the particle size measurement in the range between 0.2- 100 μ m. The particle size can be determined in terms of various diameter as shown in Fig.2.

9. Fig.2.Optical Microscopy 1. Martin’s diameter: Is the length of line that bisect the particle image. The line can be drawn in any direction, but must be in the same direction for all particle measurement. 2. Feret’s Diameter: Is the distance between two tangent on opposite site sides of particle parallel to same fixed direction. 3. Projected Area Diameter: Is the diameter of circle with same area as that of particles.

10. Disadvantages This method gives diameter of particles in 2D image. the length, width and thickness of the particles can’t be determined. The no. of particles that must be counted are in the range of 300-500 to obtain a good estimation. Thus the method is slow.

11. 2. Sieving/ Sieve Analysis (range: 40-9500 μ m) According to the method of US Pharmacopoeia for testing fineness of powder, the sieves are arranged in nest with coarsest sieve on the top i.e. the smallest sieve no. at the top. A carefully weighed sample of powder is placed on the topmost sieve and then the sieve are shaken for predetermined period of time. The powder retained on each sieve is then weighed and the right distribution curve of powder sample can be plotted.

12. Disadvantage: In this technique, if the vigorous shaking is done, the particle may break leading to generation of time and creating errors in the result.

13. 3. Sedimentation (Range: 0.08-300 μ m) In this method the terminal settling velocity of particles through a sample medium in gravitational centrifugal environment is to be measured by Andreasen Apparatus. This method is based on Stoke’s law, V= h/t = ( ƍ - ƍ o ).g 18 ɳ o V = Velocity of settling h = Distance of fall of particle in time ‘t’ d = Mean diameter of particle based on velocity of sedimentation ƍ = Density of particle ƍo = Density of dispersion medium g = Acceleration due to gravity ɳo = Viscosity of dispersion medium  

14. Fig.3. Andreasen Apparatus It consist of 550 ml vessel containing 10 ml pipette placed in cylinder its lower tip is 20 cm below the surface of suspension.

15. Particle Volume Measurement ( Range: 0.5-300 μ m) This instrument operates on the principle that when a particle is suspended in conducting liquid passes through a small orifice on side of electrode, a change in electric resistance occurs.

16. = Fig.4. Particle Volume Measurement

17. Derived Properties Of Powder Porosity Packing Arrangement Densities of Powder Bulkiness

18. 1. Porosity: V= V b - V p Bulk Volume (V b ) True Volume (V p ) It is defined as ratio of void volume to the bulk volume Expressed by equation, ϵ = V b – V p / Vb = 1 – V p /V b 2. Packing Arrangement : Two types of packing arrangements- Closest or rhombohedral packing Open or Loosest packing

19. 3. Bulkiness : The reciprocal of bulk density is called as bulkiness. It plays an important role in packing of the powders. As the bulkiness increases with decrease in particle size.

20. Factors affecting flow properties of powders Particle Size Shape of particles Density Surface texture

21. Application of Micromeritics 1. Release and Dissolution: Particle size and surface area influences the release of drug from dosage form. Higher surface area allows intimate contact of the drug with the dissolution fluids in vivo and increase the drug solubility and dissolution. 2. Absorption and Drug action: Particle size and surface area influences the drug absorption and subsequently the therapeutic action. Higher the dissolution, faster the absorption and hence quicker and greater the drug action.

22. 3. Physical Stability: The particle size in a formulation influences the physical stability of the suspension and emulsion. Smaller the size of particles, better the physical stability of dosage form. 4. Dose Uniformity: Good flow properties of granules and powders are important in the manufacturing of tablet and capsules.

23. Case Study

24. ABSTRACT The present study enlightens to enhance the dissolution profile, absorption efficiency and bioavailability of water insoluble drugs like lovastatin. A novel “Powder Solution Technology” involves absorption and adsorption efficiency, which makes use of liquid medications admixed with suitable carriers and coating materials and formulated into a free flowing, dry looking, non adherent and compressible powder forms. Based upon a new mathematical model expression improved flow characteristics and hardness of the formulation has been achieved by changing the proportion of carrier and coating material.

25. MATERIAL AND METHODS MATERIAL Lovastatin conc. in PEG, Micro crystalline cellulose, Aerosil , Crospovidone , Sodium starch glycolate , Magnesium stearate METHODS 1. Angle of repose The angle of repose physical mixtures of liquisolid compacts were determined by fixed funnel method. The accurately weighed physical mixtures of liquisolid compacts was taken in a funnel. The height of the funnel was adjusted in such a way that the tip of the funnel just touches the apex of the heap of the powder. The powder was allowed to flow through the funnel freely into the surface. The height and diameter of the powder cone was measured and angle of repose was calculated . Tan θ= h/r Where , θ is the angle of repose h is the height in cms r is the radius in cms .

26. Standard Values for Angle of Repose 25-30 Excellent flow 31-35 Good flow 36-40 Fair flow 41-45 Passable flow

27. 2. Bulk Density The loose bulk density and tapped density were determined by using bulk density apparatus. Apparent bulk density was determined by pouring the blend into a graduated cylinder. The bulk volume (Vb) and weight of the powder (M) was determined. The bulk density was calculated using the formula, Db =M/Vb Where , M is the mass of powder Vb is bulk volume of powder 3. Tapped Density The measuring cylinder containing a known mass of blend was tapped for a fixed time. The minimum volume ( Vt ) occupied in the cylinder and the weight (M) of the blend was measured. The tapped density was calculated using the formula, Dt = M/ Vt Where , M is the mass of powder Vt is tapped volume of powder

28. 4. Carr’s Index (%) The compressibility index has been proposed as an indirect measure of bulk density, size and shape, surface area, moisture content and cohesiveness of material because all of these can influence the observed compressibility index. The simplest way for measurement of free flow of powder is Carr’s Index, a indication of the ease with which a material can be induced to flow is given by Carr’s index (I) which is calculated as follows: CI (%) = [(Tapped density – Bulk density ) / Tapped density]x100 1-10 % Excellent flow Characteristic 11-15% Good flow 16-20% Fair to passable 21-25% Passable

29. 5. Hausner’s ratio Hausner’s ratio is an indirect index of ease of powder flow. It is calculated by the following formula. Hausner’s Ratio=Tapped density / Bulk density Standard Values of Hausner’s ratio: Less than 1.25 Better flow 1.25 to 1.5 Moderate flow More than 1.5 Poor flow

30. RESULTS AND DISCUSSION: F1 , F3, F5 and F7 angle of repose is between 30 ᵒ to 35ᵒ. carr’s index range between 12 to 15. Housner’s ratio1.12 to 1.18. it indicates the good flow properties. F2,F4 and F6 angle of repose in between 35ᵒ to37ᵒ. Carr’s index Between 16 to 20. Housner’ratio1.19 to 1.25. It indicates passable flow properties . Parameters F1 F2 F3 F4 F5 F6 F7 Angle of repose 33.1±0.2 37.9±0.7 35.5±0.6 37.9±0.7 35.5±0.6 37.9±0.7 33.1±0.2 Bulk density ( gm /cc3) 206.5±1.6 303.7±1.6 308.3±1.4 303.7±1.6 308.3±1.4 303.7±1.8 308.3±1.4 Tapped density ( gm /cc3) 235.7±0.2 379.6±1.2 359.7±1.6 379.6±1.2 359.7±1.6 379.6±1.4 359.7±1.6 Carr’s index(%) 12.5±0.6 19.9±0.3 14.2±0.3 19.9±0.3 14.2±0.3 19.9±0.5 14.2±0.3 Hausner’s ratio 1.14±0.02 1.24±0.02 1.16±0.01 1.24±0.02 1.16±0.01 1.24±0.01 1.14±0.04

31. CONCLUSION The present study gives an idea about the determination or evaluation of micromeritic properties of lovastatin drug and the basic idea about the methods which were used to determine the particle size of powder and the granules. Also the flow properties and the factors which affect on the flow of the powders and granules.

32. References M artin’s Physical P harmacy and Pharmaceutical S ciences, P atrick J. S inko , Sixth E dition. Y . D ivya bharathi and V. B. R ajesh, World J ournal of Pharmaceutical R esearch, Enhancement S olubility of Lovastatin D rug by using liqui -solid technique, volume 6, issue 17, 567-587.