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.