Investigating the heat sensitivity of frequently used excipients with varying particle sizes

Abstract

During tablet manufacturing an increase in the production temperature can lead to an alteration of tablet characteristics. In the present study, the influence of the initial particle size on the tableting behavior of ductile polymers upon temperature rise was investigated. Different grades of the respective materials were tableted at temperatures ranging from 22 to 70 °C. Alterations in tableting behavior were affected by the initial particle size. Smaller particle sizes led to a more pronounced decrease in yield pressure and net work of compaction during compressibility analysis. The results were confirmed in the tabletability studies. Tablets from binary mixtures with lactose containing smaller polymer particles yielded a stronger increase in tensile strength. Differences in the tensile strength increase of two grades from the same material correlated with the ratio of their median particle sizes. The alteration of compactibility profiles was also particle size dependent. The increase in solid fraction was more prominent for binary mixtures containing polymers with smaller particle sizes. However, the ratio of the median particle sizes of the compared grades showed no systematic effect. The results underline the importance of controlling the structural properties of a material carefully during formulation development and production. If a formulation responds to temperature variations, an increase in particle size might be beneficial to decrease its heat sensitivity.

Keywords: Compactibility; Energy analysis; Heated tableting; Heckel analysis; Particle size; Tabletability.