A discriminatory intrinsic dissolution study using UV area imaging analysis to gain additional insights into the dissolution behaviour of active pharmaceutical ingredients

Abstract

For efficient and effective drug development it is desirable to acquire a deep understanding of the dissolution behaviour of potential candidate drugs and their physical forms as early as possible and with the limited amounts of material that are available at that time. Using 3–10mg sample quantities, the ability of a UV imaging system is investigated to provide deep mechanistic insight into the intrinsic dissolution profiling of a range of compounds and physical forms assessed under flow conditions. Physical forms of indomethacin, theophylline and ibuprofen were compressed and their solid-state form confirmed before and after compression with X-ray methods and/or Raman spectroscopy. Intrinsic dissolution rates (IDRs) were determined using the compact's UV-imaging profile. The ratio in the IDRs for theophylline anhydrate over hydrate was 2.1 and the ratio for the alpha form of indomethacin over the gamma form was approximately 1.7. The discriminatory power of the novel UV area visualisation approach was shown to be high in that process-induced solid-state dissolution differences post-micronisation could be detected. Additionally, the scale-down system was able to visualise a previously observed increase in ibuprofen IDR with an increase in concentration of sodium dodecyl sulphate. The mechanistic dissolution insights from the visualisation approach are evident.