Influence of solid phase and formulation processing on stability of Abbott-232 tablet formulations

Area of Science:

• Pharmaceutical Sciences
• Solid-State Chemistry
• Drug Formulation

Background:

• Abbott-232, a potent uroselective alpha(1A) agonist, was selected for development.
• Initial solid-state characterization identified anhydrate, monohydrate, and amorphous phases.

Purpose of the Study:

• Investigate chemical instability in prototype immediate-release (IR) tablets.
• Determine the cause of instability, hypothesized to be process-induced phase transformation.
• Develop a stable formulation for clinical trials.

Main Methods:

• Solid-state characterization of Abbott-232 polymorphs.
• Excipient compatibility studies for immediate-release (IR) tablets.
• Investigation of wet granulation process using model systems and analytical techniques.
• Development and evaluation of a direct compression (DC) formulation.
• Polarized light microscopy (PLM) for solid-phase analysis.

Main Results:

• Wet granulation induced a solution-mediated phase transformation from anhydrate to amorphous Abbott-232, causing chemical instability.
• A direct compression formulation using dry processing prevented phase transition.
• PLM confirmed the anhydrate form remained unchanged in DC tablets.
• Stability studies validated the successful development of IR and extended-release (ER) tablets for clinical trials.

Conclusions:

• Process-induced phase transformation during wet granulation is a critical factor affecting Abbott-232 stability.
• Direct compression offers a viable manufacturing method to maintain the stable anhydrate form.
• Stable IR and ER formulations of Abbott-232 were successfully developed for clinical use.