Evaluation of the mechanical properties of extrusion-spheronized beads and multiparticulate systems

Abstract

Background: The mechanical properties of extrusion-spheronized beads as part of multiparticulate systems has not been adequately studied. Aim: The purpose was to study the mechanical properties of such drug beads and blends of drug beads and glycerol monostearate (GMS)-placebo beads. Method: Heckel analysis (mean yield pressure, Py), strain rate sensitivity (SRS), elastic recovery (ER), and total work of compression (TWC) studies were conducted using a PressterTM linear rotary tablet machine simulator operating at several combinations of speed and force. Results: The GMS-placebo beads exhibited the lowest Py values (9.1 ± 1.6 MPa) and TWC (1.9 ± 0.3 J) overall and these values steadily increased with increases in both applied speed and force. Although the placebo beads had the lowest ER values of 3.8 ± 0.7%, these beads showed significant time-dependent deformation behavior based on their SRS value of 70.2%. Heckel analysis showed that uncoated theophylline beads containing 58% ethylcellulose were more compressible than control beads containing 58% dicalcium phosphate dihydrate, the latter having the highest overall Py of 79.3 ± 3.8 MPa for the low speed/low force condition. Heckel plots also showed that 50:50 ratios of blends containing drug beads coated with either Surelease® or Eudragit® NE30D behaved similarly under increasing force and speed. Surelease®-coated cimetidine beads gave the highest Py, TWC, and ER values and these values were higher than Eudragit® NE30D-coated beads. The 50:50 blend ratios containing coated cimetidine beads showed higher Py, TWC, and ER values than the 60:40 ratios. Conclusion: Variation in the compressibility of different beads and blends can be attributed to excipients used in their formulation as well as to the drug bead-to-placebo bead ratio.