Effects of powder particle size and binder viscosity on intergranular and intragranular particle size heterogeneity during high shear granulation.
A study was performed in order to elucidate the effects of powder particle size and binder viscosity on intergranular and intragranular particle size heterogeneities. Granules were produced by melt granulation in a high shear mixer from each of four calcium carbonates having mean particle sizes in the range of 5.5-63.1 microm. Each of three polyethylene glycols (PEGs) having viscosities in the range of approximately 40-14,000 mPas were applied as meltable binders. The size distribution of the calcium carbonate particles in three granule size fractions (125-250, 355-500, and 800-1000 microm) was measured after disintegration of the granules. Intragranular particle size heterogeneities were evaluated qualitatively by means of scanning electron microscopy. A preferential growth of the smaller particles was found to give rise to a higher content of small particles in large granules when calcium carbonates with mean particle sizes of 11.7, 34.5, and 63.1 microm were granulated with a binder of low viscosity. The use of a binder of medium or high viscosity leads to a marked reduction of these heterogeneities. A preferential growth of larger particles was seen when calcium carbonates with mean particle sizes of 5.5 and 11.7 microm were granulated with a highly viscous binder. The use of a binder with low or medium viscosity resulted in an increased homogeneity. Intragranular particle size heterogeneities were primarily seen when 5.5 and 11.7 microm calcium carbonate particles were granulated with a highly viscous binder.
Department of Pharmaceutics, The Danish University of Pharmaceutical Sciences, 2 Universitetsparken, DK-2100 Copenhagen, Denmark. ds@dfuni.dk
Torben
T
Schaefer
Dorrit
D
Johnsen
Anita
A
Johansen
D005079:Excipients / Q000737:chemistry*; D008855:Microscopy, Electron, Scanning; D010316:Particle Size; D011208:Powders / Q000737:chemistry*; D033081:Shear Strength; D014783:Viscosity
D005079:Excipients; D011208:Powders