Extruded and spheronized beads containing no microcrystalline cellulose: influence of formulation and process variables.

The purposes of this study were to investigate the use of chitosan in the manufacture of beads by extrusion-spheronization without inclusion of microcrystalline cellulose, and to study the effect of formulation and process variables on the characteristics of the beads. Beads containing chitosan, fine particle ethylcellulose, hydroxypropyl methylcellulose (HPMC), and caffeine as the model drug were manufactured. Bead size, yield, shape, friability, density, porosity, and release studies were determined. Spherical beads with good mechanical properties could be manufactured without microcrystalline cellulose. Release studies showed that there was immediate release of drug from the beads. A five factor, half fraction screening design was employed to study the effect of formulation variables and process variables on the properties of the beads. Statistical analysis indicated that formulation variables such as the chitosan content, HPMC content, and water content, and process variables such as the spheronizer speed and extruder speed significantly affected the physical properties of the beads. The bead size decreased with an increase in chitosan content. Significant two-factor interactions exist between the variables for several of the measured responses. Beads with high percentage yield and high sphericity can be obtained at high chitosan content, and low HPMC content, water content, spheronizer speed, and extruder speed. Less friable beads can be obtained at high levels of studied formulation variables and low levels of studied process variables. Beads of high density and low porosity can be manufactured at high levels of the studied formulation and process variables. Regression equations were generated using Statgraphics Plus software that can be used to develop formulations with desired bead properties. Chitosan was useful to provide beads of acceptable physical properties using water as a granulating fluid in the extrusion-spheronization process.