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

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, P(y)), strain rate sensitivity (SRS), elastic recovery (ER), and total work of compression (TWC) studies were conducted using a Presster(TM) linear rotary tablet machine simulator operating at several combinations of speed and force.

Results: The GMS-placebo beads exhibited the lowest P(y) 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 P(y) 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 P(y), 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 P(y), 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.