Chemical and Process Parameters Influencing Gelling during Pharmaceutical Wet Media Milling

Abstract

Attributed with improved patient adherence, reduced dosing frequency, and potential for reduced side effects, long-acting therapeutics (including suspension formulations) have increased in popularity as a novel dosage form. Yet, although there are appreciable patient benefits for suspension formulations, the complex top-down manufacturing process train may be derailed with unanticipated outcomes. One such outcome is a sharp increase in suspension viscosity, referred to as gelling. The scope of this commentary is a comprehensive roadmap of the literature associated with the gelling phenomenon during suspension manufacture when wet bead milling is used as the manufacturing modality. The article will examine case studies that highlight attributable parameters including formulation, process, and operator actions that directly correlate with observed manufacturing outcomes. Scientifically validated terminology and carefully selected analytical characterization of the resultant gel product have been identified as avenues for increased understanding and awareness for improved manufacturing outcomes.