Evaluating Polymer Influence on Resuspendability of Indomethacin Suspensions Produced by Microfluidization.

Abstract

Long-acting injectables improve treatment outcomes for chronic diseases by reducing dosing frequency. Long-acting injectables may be formulated as nano- or microsuspensions produced by wet bead milling and homogenization often facing physical instability. This study investigates different stabilizers' ability to prevent particle growth, caking and the influence on resuspendability. Eight different stabilizers; polysorbate 20 (PS20), polysorbate 80, poloxamer 188, poloxamer 338 (P338), polyvinylpyrrolidone K17 (PVP K17), polyvinylpyrrolidone K30 (PVP K30), vitamin E-TPGS, and sodium lauryl sulphate and one potential resuspending agent (polyethylene glycol 4000) was used to assess the stability and resuspendability of indomethacin suspensions. The stability and resuspendability was assessed during four weeks of storage at three different temperatures for all stabilizers at five different concentrations. PVP K30, PVP K17 and P338 yielded stable indomethacin suspensions with minor particle growth. Statistical and machine learning modelling identified stabilizer type as a critical factor influencing resuspendability. Increased storage temperature was found to negatively impact resuspendability, particularly in formulations containing polysorbates. Addition of the resuspending agent PEG4000 did not have significant impact on the resuspendability of vitamin E-TPGS and PS20 formulations while it had a negative effect on the resuspendability of formulations with PVP K30 and P338.