Bulk Powder Properties PHA114 2024 PDF

MPharm Programme Preformulation- Bulk Powder Properties Dr Paul Carter Slide 1 of 30 MPharm Preformulation- Bulk Powder Properties  Powder packing powders can take up a variety of packing states...

MPharm Programme Preformulation- Bulk Powder Properties Dr Paul Carter Slide 1 of 30 MPharm Preformulation- Bulk Powder Properties  Powder packing powders can take up a variety of packing states loosely packed powders – contain a maximum of airspace between particles and minimum of contact points tightly packed powders – minimum air entrapped & maximum interparticulate contact powders expand and contract between these limits term ‘porosity’ refers to relative amount of air entrapped between particles porosity depends on shape and size (small particles fill voids between large particles) roughly 75 % coarse and 25% fine gives densest packing arrangement Slide 2 of 30 MPharm Preformulation- Bulk Powder Properties  powder packing (isotropic shapes) Cubical packing, Rhombohedral packing, Porosity approx. 48% Porosity approx. 26% Slide 3 of 30 MPharm Preformulation- Bulk Powder Properties  Influence of shapes (cubes) Porosity, approx 55% Porosity, 0% Slide 4 of 30 MPharm Preformulation- Bulk Powder Properties  Coarse & fine particles Increase in packing density Slide 5 of 30 MPharm Preformulation- Bulk Powder Properties  Determination of porosity powder placed in measuring cylinder without any vibration or disturbance – loosest packing state. this volume known as3‘poured bulk volume’ or ‘maximum bulk volume’ = Vb (cm /g) recipricol known 3as ‘poured bulk density’ or ‘minimum bulk density’ ρb (g/cm ) assume particles have no internal pores or capillaries void volume = v = vb - vp where vp is the particle volume (cm3/g, assuming solid particle – no pores/capillaries) porosity given by ε = (Vb – Vp)/ Vb = 1- (Vp/ Vb) also, ε = 1− k, where k = packing fraction (bulk density/true density) porosity often expressed as % since often don’t know if particles have internal pores/capillaries, ε better termed ‘apparent porosity’. True density difficult to assess Slide 6 of 30 MPharm Preformulation- Bulk Powder Properties  Determination of tapped density Tap volumeter Measuring cylinder Holder/clamp Cam to provide tapping Slide 7 of 30 MPharm Preformulation- Bulk Powder Properties  Bulk density poured powder Consolidated powder Lowest bulk density Highest bulk density Highest volume Lowest volume Slide 8 of 30 MPharm Preformulation- Bulk Powder Properties  Determination of tapped density powders placed in cylinder on tapping volumeter tapped until volume constant rotating cam at base lifts cylinder then drops it down during fall, particles will have all interparticulate forces removed and hence rearrange position final volume = minimum bulk volume’ or ‘tapped volume’ = Vt recipricol values will be ‘maximum bulk density’ or ‘tapped density’ ρt. use to measure dynamic powder packing i.e. monitor change of packing density with time (no. of taps) Slide 9 of 30 MPH116 Preformulation- Bulk Powder Properties  Powder flow properties Packing and flow are closely related interparticulate forces will give: - a larger difference between poured and tapped densities - increase in number of taps required to give tightest packing state Carr’s compressibility index and Hausner ratio use powder packing data to estimate powder flow Carr’s compressibility index (%) = (Tapped density – bulk density) x100 Tapped density note: (Initial volume – final tapped volume) x100 Initial volume Slide 10 of 30 MPH116 Preformulation- Bulk Powder Properties  Carr’s compressibility index Carr’s index (%) Type of flow 5 – 15 Excellent 12 – 16 Good 18 –21 Fair to passable* 23 –35 Poor 33 –38 Very poor > 40 Extremely poor * may be improved by glidant. (e.g. 0.2% Aerosil) Slide 11 of 30 MPharm Preformulation- Bulk Powder Properties  Hausner ratio Hausner ratio = tapped density poured density value less than 1.25 indicates good flow (= 20% Carr), value greater than 1.5 indicates poor flow (= 33% Carr). between 1.25 and 1.5, added glidant normally improves flow. >1.5 added glidant doesn’t improve flow Slide 12 of 30 MPharm Preformulation- Bulk Powder Properties  example Table 1. Bulk powder characteristics (n=3). 100g used for bulk density measurements Slide 13 of 30 MPharm Preformulation- Bulk Powder Properties  Description of results in table 1 lactose good flow and others poor Corn starch has 35% drop in volume on tapping, suggests cohesive powder (low aspect ratio) Lactose has low volume drop and particles large enough not to be cohesive (i.e. too large for attractive forces to be significant. Also lactose not hygroscopic – moisture not influencing flow) Microcrystalline cellulose has 33% volume drop, probably due to rod shaped particles (AR>1.7) - gives very low poured bulk density (0.29 g/ml) – characterised as ‘bulky’ (anything