Rheology and filling characteristics of particulate dispersions in polymer melt formulations for liquid fill hard gelatin capsules.

The rheology and capsule filling properties of molten excipients, Dynafill, Dynasan-114. Lutrol-F68, and polyethylene glycols (PEG) 6000, 8000, 10,000, and 20,000 have been investigated. Lactose (alpha-monohydrate) was selected as a model particulate solid with low solubility in PEG in order to investigate the effects of disperse phase particle size, concentration, and PEG molecular weight on rheology and capsule filling properties of these systems. All excipients behaved as Newtonian fluids between 65 and 90 degrees C, which was chosen as a possible temperature range for liquid filling of hard gelatin capsules. The excipients, apart from Dynasan-114 and PEG 20,000, showed satisfactory capsule filling properties at 70 degrees C using a semi-automatic filling machine. Dynasan-114 (viscosity = 0.012 Pa.s at 70 degrees C) leaked from the seals between the hopper and pump of the filling machine, whereas PEG 20,000 (viscosity = 24 Pa.s at 70 degrees C) showed bridging of the molten polymer between successive capsule bodies during the filling process. The effect of disperse phase (lactose) particle size and concentration, and continuous phase (PEG) molecular weight on the apparent viscosity and filling properties of the non-Newtonian dispersions were investigated at 70 degrees C. Satisfactory filling of the dispersions was achieved at 70 degrees C up to a limiting concentration of disperse phase which was dependent upon disperse phase particle size and continuous phase molecular weight, and corresponded to a pronounced increase in apparent viscosity of the dispersion.