Compaction of, and drug release from, coated drug pellets mixed with other pellets

Tablets have been prepared at known compaction force from three types of pellets in different proportions: (1) pellets containing 80% theophylline as a model drug coated with different thicknesses of a polymer film coat, (2) pellets containing glyceryl monostearate as a deformable material, and (3) pellets containing a disintegrant. The breaking load, friability, disintegration and drug release properties were evaluated, the latter as a mean dissolution time (MDT) and its variance (VDT). The mechanism of dissolution was assessed from the value of the relative dispersion (RD) of the mean dissolution time. The possible relationship between the properties of the pellets and those of the tablets was evaluated by canonical analysis followed by multiple regression analysis. It was found that only about 51% of the tablet properties could be predicted from the properties of the pellets. The quantitative relationship between pellet properties and tablet properties was found to vary in type and level of quality. Reduction of breaking load, friability and disintegration was less predictable than that of dissolution represented as the MDT. The values of RD for the different preparations clearly identified those preparations where the film coat still retained control of the dissolution process. Such formulations contained at least 40% of soft pellets and coated pellets with at least a weight gain of 8%.