Technical note on the impact of particle flocculation on the dissolution and bioavailability of triamcinolone...

Ensuring drug product quality depends on understanding and controlling the variability of quality attributes that can have a clinically relevant impact. Triamcinolone acetonide (TA) suspension for injection constitutes a widely-used class of long-acting injectables (LAIs) that can exhibit considerable variability in systemic pharmacokinetic (PK) response after intra-articular (i.a.) or intra-muscular (i.m.) administration. Syringe-induced shear (caused by needle gauge and infusion rate variations) during the administration of the injectable drug product is known to impact the dissolution of the suspended TA particles. In this work, clinical data from several regulatory submissions for TA suspensions were drawn on to demonstrate that appreciable systemic PK variability was still observed in cases where syringe needle gauge size was controlled for. Factors that might explain the observed PK variability, the injectability of LAI suspensions and shear viscosity measurements were also discussed.