Probing The Source Of An Unstable Impurity And Controlling Its Formation At Release

By Geraldine Su, Ken Strassberger, Craig Kramer, Xinqun Huang, Mike Markham, Adare Pharma Solutions

APT-76 is an anti-neoplastic agent and currently being developed as an extended-release formulation (enteric coating) for an ongoing early Phase 1 clinical trial. The finished drug product is a capsule filled with mini tablets. Two major issues related to impurities were encountered during the formulation and analytical stages.

Objectives

A critical step in an extended-release drug product analysis is the extraction during impurity and assay sample preparation. When both the drug substance and the impurity are unstable, this is especially challenging. This study is divided into three parts:

1. Identification of the unstable impurity by LC/MS, and its mechanism of the formation.
2. Probing the source of impurity formation during the extraction and manufacturing process.
3. Improving the processing and extraction method to eliminate the formation of the impurity.