Frequency analysis of stress relaxation patterns reveals the effect of formulation and process history on tablet disintegration

Abstract

Tablets are the most common pharmaceutical dosage form. Being compressed from smaller particles or granules, the disintegration rate of tablets in the gastro-intestinal tract is a key property that strongly influences the rate of drug release. While established methods for in vitro tablet disintegration measurement provide information about the final disintegration time, a more detailed analysis of the disintegration process can be a rich source of additional information. In this work, a new method of tablet disintegration monitoring based on real-time recording of stress relaxation curves in tablets after immersion in the dissolution medium is presented. The signal is recorded using a texture analyzer with a needle probe, and then processed to reveal structural changes in the disintegrating tablet. It is shown that the frequency and amplitude of fluctuations on the stress relaxation curve are uniquely able to capture parameters such as the disintegrant content and the particle size of the drug and excipients from which the tablet was made. Moreover, the method is highly sensitive to variations in the composition of dissolution media; it can therefore be used during formulation development, biopharmaceutical analysis and for the general understanding of process-property relationships of compacted granular materials.