A Study of the Effects of Curing and Storage Conditions on Controlled Release Diphenhydramine HCl Pellets Coated with Eudragit® NE30D

The objective of this study was to investigate the possible impacts of curing and storage conditions on dissolution of controlled release diphenhydramine HCl pellets coated with EUDRAGIT NE30D. The accumulative percentage of dissolved active drug was used as the response in three statistical experimental design studies: 32 full factorial, Box-Behnken and 2(3) designs. By only considering curing temperature and curing time, both factors were found to significantly affect the dissolution rate, but curing temperature had greater impact than curing time. When considering polymer coating level, curing temperature and curing time together, polymer coating level and curing temperature had important effects on dissolution rate, but curing time became insignificant among these three factors. The addition of the water-soluble additives hydroxypropyl methyl cellulose and mannitol made coating films less sensitive to curing, and there was little or no difference in their effect in the model studied. Lower levels of a water-insoluble additive (kaolin) had little impact on dissolution; however, when the level of water-insoluble additive increased, the coating film became more sensitive to curing, especially at the lower curing temperature of 30 degrees C.