Effect of Amount of Added Water During Extrusion-Spheronization Process on Pharmaceutical Properties of Granules

Abstract

In order to clarify mechanism of spherical granulation using a spheronizer and its pharmaceutical properties, crystalline lactose, corn starch and theophylline were used as pharmaceutical powders, with an aqueous solution of hydroxypropylcellulose as a binder. The granules were prepared by extruding wet masses containing various amounts of water (150, 200 and 250 ml/kg). They were treated in a spheronizer for 0–10 min, and dried at 60°C for 12 min in a fluidized-bed dryer. The elongation ratio was used as an index of spheronization, and the arithmetic mean granules diameter were used as mean daimeter. The elongation ratio of the granules decreased from 5–8 to around 1.5 after 2-min spheronization. The angle of repose of spheronized granules was lower than that of the intact granules, suggesting that they had better flowability. The yield of granules obtained from addition of 250 ml/kg of water was much higher than that by adding 150 ml/kg of water, indicating that the former had a larger mean particle size than the latter. The result of mercury porosimetry showed that the amount of water in the binder solution affected the internal porosity of the spherical granules; it increased with decreasing internal porosity. The friability test suggested that the weight loss after the test was affected by the amount of water added, and it increased with decreasing amounts of water. Therefore, the quantity of water added to the granules influenced the mechanical strength of the granules. On the other hand, the hardness of tablets prepared by using a compressor at 2500 kg/cm² seemed to increase with a decrease in the mechanical strength of intact granules. And, tablets prepared from harder granules showed a capping tendency. Practical tabletting simulation using an eccentric type tabletting machine yielded the same results as those obtained by static compression.