Use of Resonant Acoustic Mixing Technology for Ultra-Low-Dose Blending in a Single-Step Mixing Process

Area of Science:

• Pharmaceutical Technology
• Materials Science
• Chemical Engineering

Background:

• Achieving blend uniformity (BU) for low-dose active pharmaceutical ingredients (APIs) with challenging morphologies is critical in pharmaceutical manufacturing.
• Traditional mixing methods often struggle with achieving homogeneity at very low concentrations (<0.1% w/w).
• Resonant Acoustic Mixing (RAM) technology offers a potential solution for advanced powder mixing challenges.

Purpose of the Study:

• To evaluate the efficacy of RAM technology for homogenous blending of a morphologically challenging model API at low concentrations (<0.1% w/w).
• To assess the potential for optimizing blend uniformity (BU) using RAM.
• To determine the capacity for microscale mixing and reproducible dosing of single-digit microgram drug amounts.

Main Methods:

• Utilized a LabRAM I benchtop mixer employing resonant acoustic mixing (RAM) technology.
• Caffeine (CAF) was used as a model API, mixed at concentrations of 0.05% and 0.0125% w/w.
• Optimized mixing conditions and sample preparation procedures to assess system performance and BU.

Main Results:

• RAM successfully produced homogenous mixtures of <0.1% CAF, achieving dilutions up to 1 part per 8,000.
• A 0.0125% w/w CAF blend accurately prepared 25 μg of CAF with 99.3% accuracy (98.7% label claim).
• Microscale mixing was confirmed, with blend uniformity criteria failing only at 2 μg CAF, demonstrating suitability for microgram dosing.

Conclusions:

• This study demonstrates the first successful homogenous blending of <0.1% (w/w) API using RAM technology.
• RAM technology is suitable for reproducible dosing of single-digit microgram drug amounts, even with challenging APIs.
• The achieved uniformity for API amounts is significantly smaller than previously reported for caffeine (CAF) and other methods.