(W1030-01-01) Investigating the Relationship between Material Attributes of API and the Extent of Powder Property Enhancement via Dry Particle Coating with Nano-Silica

Purpose: Dry particle coating with nano-silica has been employed to improve the flow properties of cohesive APIs. However, the extent of powder flow enhancement can be case-dependent, relating to a variety of factors. The purpose of this work is to investigate the relationship between material attributes of API and potential improvement in bulk powder properties.

Methods: Eight model cohesive Genentech APIs with varying particulate and bulk properties were used. Dry coating was performed for blends of APIs with Aerosil 200 or Aerosil R972 at a 20 gram scale, using a LabRAM Acoustic Mixer (60 G, 5 minutes). Particle morphology (SEM), specific surface area (BET), surface energy (IGC with dispersive/non-polar and acid-base/polar probes), flow function coefficient (FFC), and bulk density were characterized for coated API with different levels of each grade of Aerosil (0, 0.5, 1, 1.5, 2% w/w).

Results: The extent of powder flow improvement differed greatly for coated APIs, ranging from insignificant up to 2-3 fold increases (Figures 1, 2). Aerosil R972 generally showed greater propensity for improvement as compared to Aerosil 200. Changes in bulk density after dry coating did not correlate strongly with powder flow improvement across all APIs, including cases where values decreased slightly to 1.3-fold increases. However, those APIs with the greatest powder flow improvement also showed the greatest improvement in bulk density values. SEM analysis revealed a strong correlation between greater powder flow improvement and the uniform distribution of Aerosil particles on the API particles. After dry coating, more Aerosil R972 particles remained associated with API particles and spread more uniformly across API particles, whereas Aerosil 200 appeared as agglomerates unevenly associated with API particles. The SEM-related observations correlated strongly with powder flow improvement. In one case, higher levels of Aerosil were detrimental to powder flow, as this correlated with multiple Aerosil layers (visible by SEM, Figure 3) associated with the API surface. Theoretical calculations for the amount of Aerosil required for powder coating of various Genentech APIs correlated with tested ranges (0.5% to 2% w/w).

Conclusion: It is important to investigate the impact of material attributes on the effectiveness of the dry particle coating approach, which provides insight and understanding on the selection of suitable technology and excipients to improve the flow properties of cohesive powders. This work has shown that API properties can be significantly improved and should be further investigated to determine more suitable cases for the successful application of this technology.

Figure 1. Bulk powder flow (FFC) for GDC APIs after dry particle coating with Aerosil 200

Figure 2. Bulk powder flow (FFC) for GDC APIs after dry particle coating with Aerosil R972

Figure 3. SEM analysis of GDC-4 after dry particle coating with various levels of Aerosil 200 or R972