Searching for Evidence of Changes in Interparticle Bonding in Comressed Pellets

Abstract

This study surveys the relationships found between dissolution, hardness and disintegration characteristics of formulated sucrose tablet compacts in an attempt to determine the effects of interparticle bonding on these physicochemical parameters. In general, dissolution stability is defined as the retention of the dissolution characteristics of a solid oral dosage form from the time of manufacture to its expiration date. It is a critical parameter from the standpoint of quality control, regulatory compliance and its potential impact on the bioavailability of a product. To elucidate our understanding of the role of moisture and initial compressional force on tablet hardness and their subsequent effects on important tablet parameters, most commonly used placebo excipients like Mendell's Sugartab, microcrystalline cellulose and magnesium stearate were used. The data suggests that moisture and compressional force clearly play a significantly important role in controlling hardness of compressed tablets after storage. As a consequence of partial moisture gain from humidity exposure, an increase in hardness was observed. Such hardness increases also decrease the disintegration time as well as the in vitro drug dissolution half-time. Since the important parameter, in vitro dissolution of the tablets, is related to the moisture content of the exposed formulation with high correlation, an in vitro dissolution specification would ensure that the tablets did meet moisture, disintegration and hardness requirements as well. Similar results were found in the compressional force experiments, yet these results showed even higher correlations. Finally, the data suggests that the magnitude of the moisture related hardness increase depends on the physical properties of the drug and/or excipient combinations.