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.


OBJECTIVE
The purpose was to study the mechanical properties of such drug beads and blends of drug beads and glycerol monostearate (GMS)-placebo beads.


METHODS
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.


CONCLUSIONS
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.
Cantor
Stuart L
SL
School of Pharmacy, University of Maryland, Baltimore, MD 21201, USA.
Hoag
Stephen W
SW
Augsburger
Larry L
LL
D002482:Cellulose / Q000031:analogs & derivatives / Q000737:chemistry; D002927:Cimetidine / Q000008:administration & dosage / Q000737:chemistry*; D005079:Excipients / Q000737:chemistry*; D005989:Glycerides / Q000737:chemistry*; D008689:Methacrylates / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D013607:Tablets; D013678:Technology, Pharmaceutical / Q000379:methods; D013806:Theophylline / Q000008:administration & dosage / Q000737:chemistry*; D013997:Time Factors
C477853:Eudragit NE 30-D; D005079:Excipients; D005989:Glycerides; D008689:Methacrylates; D011108:Polymers; D013607:Tablets; C048159:glyceryl monostearate; C013517:ethyl cellulose; D002927:Cimetidine; D002482:Cellulose; D013806:Theophylline