Assessment of Resonant Acoustic Mixing for Low-Dose Pharmaceutical Powder Blends

Abstract

Obtaining a homogeneous low-dose pharmaceutical powder blend without multi-step processing remains a challenge. One promising technology to address this risk is resonant acoustic mixing (RAM). In this study, the performance of a laboratory resonant acoustic mixer (LabRAM) was studied at low active pharmaceutical ingredient (API) concentrations (0.1-0.5% w/w), using three commercial grades of a model API (Acetaminophen) and diluents with varying physical properties. The performance was assessed by evaluating blend uniformity (BU) and capsule content uniformity (CU) as a function of mixing time. Overall, the LabRAM achieved acceptable BU in a single step even at 0.1% w/w drug loading. A reduction in API primary particle size led to improved mixing efficiency and uniformity. Moreover, the presence of surface cavities in the diluents used appeared to have led to improved uniformity. The results demonstrated that RAM could achieve uniform powder blends without multi-step processing, for low-dose formulations.

Keywords: API particle size; Blend uniformity; Diluent surface; Low dose; Resonant acoustic mixing (RAM).