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Its all about small particles


Chaitanya swaroop mata

October 02, 2012


  1. Micromeritics I T ’ S   A L L  

    A B O U T   S M A L L   P A R T I C L E S  
  2. What  is  Micromeritics?   •  The  Science  and  Technology  of

     small  particles  is   known  as  Micromeritics.                 Micromeritics  deals  with:   •  Particle  size  and  Size  Distribution     •   Methods  of  Determining  particle  size   •   Particle  shape  and  surface  area   •   Pore  size  
  3. Micromeritics   •  Units  of  particle  size  is  Micrometers  (μm)

      •  μm  =  μ  =  10-­‐6m   •  As  particle  size  decreases,  surface  area  increases   •  Can  be  related  to  physical,  chemical  and  pharmacological   properties  of  drugs.    
  4. Micromeritics   1.  Release   &   Dissolution   :

      Higher   surface   area   allows   intimate   contact  of  the  drug  with  the  dissolution  fluids  in  vivo  &  increases   the  drug  solubility  &  dissolution.     2.  Absorption   &   Drug   action:   Higher   the   dissolution,   faster   the   absorption  &  hence  quicker  &  greater  the  drug  action.        
  5. Micromeritics   3.  Physical  stability:  Smaller  the  size  of  the

     particle,  better   the  physical  stability  of  the  dosage  form.     4.  Dose   uniformity:   Good   flow   properties   of   granules   &   powders   are   important   in   the   manufacturing   of   tablets   &   capsules.      
  6. Particle  size  determination  by  Microscopic   Method   Size  group

     of  counted   particles  /  µm   Middle  value  µm    “d”   Number  of  particles  per   group  “n”   “nd”   40-60 50 15 750 60-80 70 25 1750 80-100 90 95 8550 100-120 110 140 15400 120-140 130 80 10400 ∑n=355   ∑nd=36850   8 . 103 355 36850 n nd d av = = = ∑ ∑
  7. Particle  size  determination  by  Sieving  Method   Sieve  number  

    Arithmatic  mean   opening  (mm)   Weight  Retained     “G”   %  Retained   %  Retained     X  mean  opening   20/40 0.630 15.5 14.3 9.009 40/60 0.335 25.8 23.7 7.939 60/80 0.214 48.3 44.4 9.502 80/100 0.163 15.6 14.3 2.330 100/120 0.137 3.5 3.3 0.452 108.7 100.0 29.232 ( ) ( ) mm 2923 . 0 100 232 . 29 100 size avg retained % d avg = = × = ∑
  8. None
  9. None
  10. Micromeritics  -­‐  Methods   Methods  of  determining  particle  size:  

    •  Optical  Microscopy     •  Sieving  Methods   •  Sedimentation  Methods   Particle  volume  measurement:   •  Coulter  Counter  Method  (Electrical  stream  sensing  method)   •  Laser  light  scattering  methods.     Methods  of  determining  surface  area:   •  Adsorption  method   •  Air  permeability  method  
  11. Microscopy       0.2  to  100  μm  provide  information

     of  shape  also     Principle  of  operation   1.  Optic  or  electronic  measures   2.  Two  dimensional  projection   3.  Projection  screen  or  circles   4.  Image  analysing  programs   5.  Measures   6.  Feret  diameters     7.  Equal  circles   8.  Size  range-­‐  0.001-­‐1000  µm   9.  Gives  number  average,  or  area   average  
  12. Benefits   •  “Simple”  and  intuitive   •  Give  shape

     information   •  Reasonable  amount  of  sample   Drawbacks   •  Statistic  relevance  “tedious”  if  image  analyse  can  not  be  used   •  Risk  for  bias  interpretation   •  Difficult  for  high  concentrations   •  Sample  preparation  might  be  difficult  
  13. Sieving  Method   Sieving  method  is  an  ordinary  and  simple

     method.  It  is  widely  used  as  a  method  for  the  particle   size  analysis.   Range  of  analysis:   The  International  Standards  organization  (ISO)  sets  a  lowest  sieve  diameter  of  45  µm  and  since   powders   are   usually   defined   as   having   a   maximum   diameter   of   1000   µm,   this   could   be   considered  to  be  the  upper  limit.     In  practice  sieves  can  be  obtained  for  size  analysis  over  a  range  from  5  to  125  000  µm.                                                                                                                  0.001                              0.01                                    0.1                                              1                                                      10                                                      100                                              1000   ISO  Range   Particle  diameter      (µm)  
  14. Sample  preparation  and  analysis  condition   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   Advantages:       1.  This  method  is  very  simple   2.  Not  expensive   3.  Easy  to  operate                                   Disadvantages:     1.  Not  too  much  precise  method.   2.  Not  applicable  for  all  disperse  systems.      
  15. Sedimentation  Methods     Sedimentation Method is also an ordinary

    and simple method. It is widely used as a method for the particle size analysis. Range of analysis: 0.001 0.01 0.1 1 10 100 1000 Centrifugal    sedimentation   Gravitational   Particle  diameter  (µm)  
  16. Principle  of  Measurement   Particle size analysis by sedimentation method

    Can be divided into two main categories according to the method of measurement used. 1. One of the type is based on measurement of particle in a retention zone. 2. Another type uses a non-retention measurement zone. One of the most popular of the pipette methods was that developed by Andreasen and Lundberg and commonly called the Andreasen pipette.
  17. Coulter  Counter  Method  (Electrical  stream  sensing  zone  method)   Coulter

    Counter Method (Electrical stream sensing zone method) is a sophisticated method. It is a precise and accurate method. Range of analysis:            0.001                            0.01                          0.1                                          1                                                      10                                                          100                                              1000   Coulter  counter   Particle  diameter  (µm)  
  18. None
  19. Other  Methods  to  Determine  Particle  Size   •  Laser  Light

     Scattering   •  X-­‐ray  Sedimentation   •  Electrical  Sensing  Zone   •  Particle  Size  by  Surface  Area  
  20. Particle  properties  &  Flow:   Particle  size  :  Larger  than

     250µ  are  free  flowing  but  as  size  falls  below  100µ  it  is   cohesive;  collection  of  powder  will  be  either                  A.  Monodisperse  (  having  particles  of  same  size  )  or                    B.  Polydisperse  (having  particles  of  more  than  one  size)   Particle  shape  :  Spheres  have  minimum  contact  &  hence  optimal  flow;  particle   flakes  have  high  surface  to  volume  ratio  &  poor  flow   Packing  geometry  :   •  Characterization  by  porosity  &  bulk  density   •  Bulk  density  is  always  less  than  true  density-­‐  due  to  interparticle  pores/voids  
  21. Derived  properties  of  powders    :        

     Apart  from  fundamental  properties,  there  are  derived  properties.  These  are   based  on  fundamental  properties.       1.  Porosity   2.  Packing  arrangements   3.  Densities   of   particles:   Dense   particles   are   less   cohesive   than   less   dense   particles  of  the  same  size  &  shape   4.  Particle  volume:  Bulk  volume,  Tap  volume,  Void  volume.  Instrument  used  for   measurement  is  coulter  counter  
  22. 5.  Particle  surface  area:  is  important  characteristic  for  understanding  surface

      adsorption  and  dissolution  rate  studies  and  can  be  studied  by                                    A.  Adsorption  method      B.  Air  permeability  method   Here  the  principle  is  “resistance  to   the  flow  of  a  fluid  through  a  plug  of   powder   is   the   surface   area   of   powder.   “Greater   the   surface   area,   the  greater  will  be  the  resistance  to   flow.   The   instrument   used   is   Fisher   subsieve  sizer.   when   a   mixture   of   helium   and   nitrogen   is   passed   through   the   cell,   containing   powder.   Here   nitrogen   is   absorbate   gas   and   helium   is   inert   and   is   not   adsorbed  on  surface.     An  instrument  used  to  obtain  data   for  calculation  of  surface  area    is     Quantasorb    
  23. 6.  Bulkiness:  Reciprocal  of  bulk  density,     7.  Flow

     properties:  Powders  may  be  free-­‐flowing    or    cohesive.                  Factors  those  affect  flow  properties  are                                      a)  particle  size,  b)  shape,  c)  porosity,    d)  density,  e)  texture.   8.        Compaction                        9.  Angle  of  repose:  [θ  =  tan-­‐(h/r)]     10.      Carr’s  Index:  (Tapped  density  -­‐  Poured  density)  x  100                                                                                                                                                                Tapped  density   11.  Hausner’s  ratio:  Tapped  density                                                                            Poured  density  
  24. Characterization  of  powder  flow   Indirect  Methods:   1.  Angle

     of  repose   2.  Shear  cell  determinations  which  gives  relationship  between  flow   factors  &  powder  flowability   3.  Bulk  density  measurements  like  %  compressibility  &  flow,  Carr’s   index   4.  Critical  orifice  diameter-­‐direct  measure  of  powder  cohesion  &   arch  strength  
  25. Direct  Methods:   1.  Hopper  flow  rate   2.  Recording

     with  flowmeter     How  to  improve  flow?   1.  Alter  particle  size  &  size  distribution   2.  Alter  particle  shape  or  texture   3.  Alter  surface  forces   4.  Formulation  additives   5.  Vibration  assisted  hoppers   6.  Force  feeders  
  26. Angle  of  Repose Estimates  the  flowability  of  a  powder.  

    µ = = r h θ tan h r θ 1.  Shape: Spherical particles flow better than needles. 2.  Size: Very fine particles do not flow as freely as large particles. a.  250-2000 µm: flow freely if the shape is amenable b.  75-250 µm: may flow freely or cause problems c.  less than 100 µm: flow is problem with most substances.
  27. Angle  of  Repose

  28. •  Hausner  ratio  greater  than  1.25  is  considered  to  be

     an  indication  of   poor  flowability.     •  The  Hausner  ratio  (H)  is  related  to  the  Carr  index  (C),  another   indication  of  flowability,  by  the  formula  H  =  100  /  (100  −  C)   •  A  Carr  index  greater  than  25%  is  considered  to  be  an  indication  of   poor  flowability,  and  below  15%,  of  good  flowability  
  29. Porosity  is  a  measure  of  the  void  spaces  in  a

     material,  and  is  measured  as  a   fraction,  between  0–1,  or  as  a  percentage  between  0–100%.     It  is  defined  by  the  ratio:    Vv   Φ  =      -­‐-­‐-­‐-­‐    VT   where  VV  is  the  volume  of  void-­‐space  (such  as  fluids)  and  VT  is  the  total  or   bulk  volume  of  material,  including  the  solid  and  void  components.    
  30. Other  characteristics  of  Micromeritics   100 Void Porosity × =

    bulk bulk V V V Void − = bulk a V sample the of weight ) (ρ density Apparent = a ρ 1 (B) Bulkiness = 100 V V V Porosity bulk bulk × − = V sample the of weight ) (ρ density True t =
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