Development of Matrix Controlled Release Beads by Extrusion-Spheronization Technology Using a Statistical Screening Design

Abstract

The objective of this study was to develop beads with inherent modified release characteristics requiring no subsequent controlled release coating. Extrusion-spheronization was chosen to accomplish this goal. The model drug was a zwitterion (isoelectric point ∼pH 5.2) with poor solubility and low bulk density. Preliminary studies indicated that matrix beads with modified micro-environmental pH would result in sustained release of the drug. A Nica extruder and spheronizer were used to manufacture the beads. A Plackett-Burman screening design was employed to isolate critical variables influencing the bead characteristics and drug release. Variables studied included the type of polymeric dispersion, polymer concentration, acid type, acid concentration, plasticizer content, drug concentration and spheronizing time. Responses evaluated included capsule fill weight, drug release rate, micro-environmental pH, yield and friability. Beads were successfully manufactured according to the screening design and exhibited different dissolution characteristics. Polymer type (Eudragit RS 30 D over Aquacoat ECD-30), polymer concentration and acid concentration significantly retarded drug release. However, increasing acid concentration increased bead friability. In addition to drug concentration, higher polymer concentration, appropriate acid selection and longer residence times afforded maximum capsule fill weights and increased bead density.