Spheronization of Theophylline-Avicel Combinations Using a Fluidized-Bed Rotogranulation Technique

Abstract

A tangential-spray rotary fluidized-bed granulator was used to test the spheronization potential of microcrystalline cellulose in a process using anhydrous theophylline as a model drug. Three grades of theophylline and three grades of microcrystalline cellulose (MCC) were used together to form spherical pellets in drug potencies up to 90%. Water was used as the granulating agent. The purpose of the investigation was to identify differences between raw materials in the formation of spheres and the effects of increasing levels of drug loading on pellet quality. The materials were judged by their ability to spheronize, while the pellets themselves were characterized by size, density, friability, flowability, drug content, and shape. There were marked differences in the ability of some combinations to form spheres. A qualitative scale of spheronization potential describes the ability of the process to go to completion without rescue. The potential for spheronization of binary systems using anhydrous theophylline and microcrystalline cellulose depended primarily on the choice of theophylline and the level of drug loading. The choice of MCC grade was less important. In concentrations of 50% drug and below, all nine combinations of drug and excipient formed spheres, although often with difficulty. The two finer grades of theophylline were substantially more difficult to spheronize than the coarse grade. Only the coarsest grade of theophylline formed spheres containing 90% drug. Despite substantial differences in spheronization potential, the pellets themselves showed similarities in true density, friability, or flowability. Other properties showed significant differences. Sphericiv declined when drug loading exceeded 70%. The actual drug content of the pellets declined slightly with increasing theoretical potency and did not vary across sieve fractions.