Methodology

Table 2 - Process conditions for Precision-Granulation™, top spray fluid bed granulation and high shear granulation trials

a) Precision-Granulation™ (PG) b) Top Spray Fluid Bed Granulation (TS-FBG)
Equipment MP 2/3, Aeromatic-Fielder Equipment MP 2/3, Aeromatic-Fielder
Batch size 5 kg Batch size 12 kg
Amount of granulating liquid 1.7 kg (15% povidone solution)unless otherwise stated Amount of granulating liquid 4 kg (15% povidone solution)
Inlet air flow volume rate 250 m3/h unless otherwise stated Inlet air flow volume rate 300 m3/h
Inlet air temperature 80°C unless otherwise stated Inlet air temperature 70°C
Column diameter 150 mm unless otherwise stated Atomizing air pressure 1 bar
Insert diameter 60 mm Spray rate 125 g/min; 162 g/min—> 120g/min (start with fast spray rate and then reduce spray rate)
Air cap area / opening Full/standard unless otherwise Drying time 8 min; 10.3 min

c) High Shear Granulation (HSG)
Granulation Drying
Equipment PMA 65, Aeromatic-Fielder Equipment MP-2/3, Aeromatic-Fielder
Batch size 18 kg Inlet air flow volume rate 500 m3/h
Amount of granulating liquid 2.7 kg (water) Inlet air temperature 70°C
Phase during granulation Impeller speed Chopper speed Drying time 18 min
Premix 300 rpm 1500 rpm Final loss on drying (LOD) 2.8%
Liquid addition 350 rpm 1500 rpm -
Wet massing 400 rpm 1500 rpm -

Settings chosen for TS-FBG and HSG were fairly typical settings for obtaining good TS-FBG and HSG/drying processes.

Table 3 - Settings for the PG trial batches
a) Lactose 200M PG trials with povidone as a wet binder
PG Batches Atomizing air pressure (bar) Column diameter (mm) Inlet air temperature Air flow volume rate (m3/h) Column velocity (m/s) Spray rate (g/min) Drying time (min) Final LOD (%)
PG 19 0.5 150 80 250 3.9 130 - 4.9
PG 23 0.25 150 80 250 3.9 140 3.3 2.5
PG 24 0.25 150 80 250 3.9 140 3.4 2.1
PG 26 0.5 150 80 250 3.9 139 4 1.9
PG 30 0.25 100 50 300 10.6 79 4 2.0

b) PG trials with 2 grades of lactose and powdered sugar
PG Batches Material Atomizing air pressure (bar) Air cap area / opening Granulating liquid - water (kg) Spray rate (g/min) Drying time (min) Final LOD (%)
PG 17 Lactose 200M 0.25 full/standard 2.53 109 3 2.8
PG 41 Lactose 450M 0.25 full/standard 3 118 2.7 2.6
PG 39 Lactose 450M 0.25 1/4 3 119 5.3 3.0
PG 44 Powdered sugar 0.25 1/4 1.5 81 2.4 2.2

Table 4 - System for ranking the quality of the lactose 200M PG, TS-FBG and HSG tablet batches

Tablet Characteristics Ranking system
Weight variation With "1" for batch with the smallest weight variation and "8" for batch with the largest weight variation.
Friability With "1" for the least friable batch (i.e. with least % weight loss) and "8" for the most friable tablet batch.
Disintegration time With "1" for batch with the shortest disintegration time and "8" for batch with the longest disintegration time.
Coefficient of variation for disintegration time With "1" for batch with the smallest coefficient of variation and "8" for batch with the largest coefficient of variation.
Coefficient of variation for hardness With "1" for batch with the smallest coefficient of variation and "8" for batch with the largest coefficient of hardness.

  • The 5 tablet characteristics were assigned equal weightage.
  • For each tablet batch, ranks of the 5 tablet characteristics were summed to determine its composite rank.
  • Tablet batches with the smallest and largest sum were assigned ratings of  "1" and "8", respectively.
  • The batch with the smallest composite rank was considered to be the most ideal batch, i.e. with the best overall tablet quality, within the group of 8 tablet batches.

Results

Granule characteristics

  • HSG granules had the widest size distribution.
  • Granule porosity increased and granule strength decreased for HSG, PG and TS-FBG.
  • Poured bulk and tapped densities decreased for milled HSG, PG and TS-FBG.
  • Angle of repose values for the granulation batches ranged from 32.5 to 35.6°.

Tablet characteristics

  • Group mean hardness and weight of the 8 tablet batches : 105.9 (±15.1) N and 282.6 (±15.3) mg.
  • PG 19 tablet batch ranked "1" in the composite ranking.
  • TS-FBG 33 batch ranked "2". TS-FBG 34, HSG 46 and PG 30 tablet batches shared the same ranking of "4".

PG feasibility trials on fine particles (lactose 450M) and powdered crystalline material (powdered sugar) with poor flow properties

Table 5 - Granule and tablet characteristics of lactose and powdered sugar PG batches
a) Granule characteristics
Granulation batches Material Mass median  dia. D50%(mm) Span Porosity (mL/g) Granule strength (N) Poured bulk density (g/mL) Tapped density (g/mL) Carr index (%) Hausner ratio Angle of repose (°)
PG 17 Lactose 200M 0.496 1.16 42.8 0.87 0.55 0.59 5.83 1.06 33.2
PG 41 Lactose 450M 0.326 1.49 43.02 0.92 0.57 0.66 13.25 1.15 34.5
PG 39 Lactose 450M 0.419 1.20 43.77 0.73 0.55 0.61 9.75 1.11 32.2
PG 44 Powdered Sugar 0.336 0.76 44.11 1.08 0.47 0.52 8.67 1.10 37.4

b) Tablet characteristics
Tablet batches Material Tablet weight (mg) Weight variation (%) Friability (%) Disintegration time (s) Coefficient of variation for disintegration time tablet hardness (N) Coefficient of variation for hardness
PG 17 Lactose 200M 282.1 3.1 0.23 158 20.4 113.1 5.4
PG 41 Lactose 450M 268.5 1.8 0.40 529 7.6 98.9 7.8
PG 39 Lactose 450M 302 1.5 0.38 640 12.1 116.0 6.0
PG44 Powdered Sugar 279.2 2.2 0.42 332 4.8 116.0 6.4

  • Both lactose 450M and powdered sugar could be granulated by PG.
  • A greater amount of granulating liquid (water) was used for preparing lactose 450M PG granules.
  • Tablets prepared from lactose 450M and powdered sugar PG granules with similar tablet weight and hardness had longer disintegration times than tablets made from the lactose 200M PG granules.
 Back  Top of page