Comparison of Regular Tablets With Mini-Tablets Prepared As An
Alternative To Pellets.
Stuart C. Porter, Gary Bubb, Dev K. Mehra, and Robert Sedlock
Purpose: To use a D.o.E. approach to examine
the influence of three formulation variables on drug release from
matrix modified-release tablets coated with various levels of
a modified-release film coating, and to explore the merits of
using mini-tablets, as an alternative to pellets, as a multiparticulate
delivery system.
Methods: Tablets (both regular 10mm standard
concave tablets, and 2mm mini-tablets) containing chlorpheniramine
maleate were produced using a Piccola 10 station, instrumented
rotary tablet press at a nominal applied pressure of 150 MPa.
Tablets of each size were film coated with an aqueous ethylcellulose
dispersion (Surelease), modified with a water-soluble polymer
system (Opadry), using a laboratory-scale fluid-bed coater fitted
with a Wurster insert. Tablet samples, selected at various levels
of applied coating, were tested for their drug-release characteristics
in deionized water, at 37ºC, using USP Apparatus 1. Resultant
drug-release profiles were examined to determine lag times, release
rates, and release kinetics.
Results: Generally, it was noted that all three
formulation variables (quantity of HPMC used in the tablet cores;
amount of film coating applied; and amount of water-soluble modifier
used in the coating) had a statistically significant effect on
the three drug-release characteristics studied. Optimized formulations,
exhibiting zero-order release kinetics and minimal lag times,
were obtained for the standard 10mm tablets, and used as the basis
for preparing, and comparison with, mini-tablets. For equivalent
values of applied compaction pressures, mini-tablets exhibited
lower tensile strength values and higher friabilities. As expected,
mini-tablets required higher levels of applied coatings, compared
to the standard 10mm tablets, in order to achieve equivalent drug-release
rates.
Conclusions: The results obtained illustrate
the value of using a statistical design of experiments approach
to optimize drug release characteristics from modified-release
matrix tablets coated with a modified-release film-coating, and
also confirm the usefulness of mini-tablets as a viable multiparticulate
drug-delivery system. |
