(T1430-11-70) Assessing the Impact of Dry Particle Coating with Nano-Silica on Compaction Properties of Cohesive Active Pharmaceutical Ingredients

Purpose: Dry particle coating with nano-silica (Aerosil) has been employed to improve the flow properties of cohesive APIs. However, its impact on powder compaction properties has not been extensively studied. The purpose of this work is to assess the impact of dry particle coating with silica on powder compaction properties of very cohesive active pharmaceutical ingredients (APIs).

Methods: Four model cohesive Genentech APIs with varying particulate and bulk properties were used. Dry coating was performed for blends of APIs with Aerosil 200 using a LabRAM Acoustic Mixer. Particle size distribution, particle morphology, BET specific surface area, surface energy, bulk and tapped density were characterized for coated APIs. A Huxley Bertram compaction simulator with an instrumented die was used to assess powder compaction properties. After compaction at pressure ranging from 50 to 250 MPa, tablet weight, thickness and hardness were determined by a semi-automatic tablet tester. Based on the measurements, compressibility, compactability, tabletability, and residual die wall pressure of the coated APIs were determined.

Results: The data shows that dry coating with increasing levels of either Aerosil 200 produced higher surface area and lower surface energy values across all tested APIs. Compaction data revealed that dry coating didn’t have significantly impact on compressibility of APIs coated with Aerosil 200 up to 2%, while compactability either remained similar or increased as compared to uncoated APIs (Figure 1). SEM analysis showed that the significant increase of compactability of GDC-4 likely due to its plate-like morphology with more uniform distribution of Aerosil particles on the API particles.

Conclusion: This work has shown that dry coating resulted in comparable or improved compaction properties of various APIs coated with Aerosil 200, which suggests that particle dry coating technology can be utilized to improve both flow and compaction properties. Future work will be performed to study more model APIs and different grade of nano-silica (e.g. Aerosil 972).

Figure 1. Compactability plots for GDC APIs after dry particle coating with Aerosil 200

Figure 2. SEM analysis of APIs after dry particle coating with 2% of Aerosil 200 a) GDC-1, b) GDC-2, c) GDC-3, d) GDC-4