(694a) Enhancing Drug Processibility through Improved Dry Coating Techniques: A Comparative Study of Lab and Pilot Scale Methods

Dry coating of pharmaceutical powders is a promising technique that can enhance their bulk properties and downstream processibility during tablet manufacturing. By applying a thin, sparse layer of nano-silica onto the surface of the powders, various beneficial effects such as improved flowability, reduced cohesion, and enhanced tabletability can be achieved. This process can be performed using different dry coating techniques, including acoustic mixing, milling, and diffusive blending. Comprehensive previous studies have investigated the efficacy of nano-silica dry coating and emphasized the importance of optimized coating parameters and specific silica types. However, further exploration is needed to understand the implementation of dry coating at different scales and its impact on downstream drug product attributes. This work focuses on evaluating the benefits of dry coating in four industrially-relevant investigations: (1) comparing the addition of nano-silica using surface area coverage (SAC) and weight percent-based approaches, (2) assessing the impact of scale-up on dry coating operations, (3) examining the benefits of dry coating on feedability of powders, and (4) investigating the enhancements of dry coating on tabletability and sticking.

Determining the appropriate amount of nano-silica needed for dry coating is critical to obtain desired processability enhancements. This study compared the traditional 1 wt.% silica addition methodology with a SAC-based approach at the lab-scale using a LabRAM acoustic mixer. A lab-scale study evaluated six materials consisting of three APIs and three excipients with particle sizes ranging from 2-40μm (d50). It was observed that dry coated powders are distinguishable and well characterized when such tests are employed which require external consolidation like FFC. Hence flow function coefficient (FFC) was found to be a reliable indicator of flowability enhancement after coating. The SAC-based approach was shown to be superior to the arbitrary 1 wt.% silica blending approach, as materials coated to 50% SAC with nano-silica content ranging from 0.5-4 wt.% displayed better flow performance. However, practical challenges were identified in determining the varying composition of nano-silica during industrial drug product development. Recommendations were provided for specific silica amounts tailored to host particle size ranges, considering the variability in size and density of host and guest particles. This workflow establishes an industrially feasible approach that provides weight percent ranges based on host particle attributes, resulting in significant flow improvements.

For scalability analysis from lab to pilot scale, a COMIL-U10 was utilized as a continuous dry coating device, focusing on three materials that required 1 wt.% silica for adequate coverage. The study aimed to investigate the efficacy of silicon dioxide dry coating techniques using COMIL-U10 and lab scale LabRAM to enhance bulk properties and evaluate their impact on downstream API processibility for tableting. Two silica variants, Cab-O-Sil M5P (hydrophobic) and Aerosil R972P (hydrophilic), were examined in terms of bulk property improvement and downstream processibility. The results indicated that the performance of pilot-scale equipment was not as efficient as lab-scale equipment, although it still provided measurable improvement in powder flow properties. Feeding tests conducted on pilot-scale coated materials (using the COMIL-U10) showed excellent improvement in feeding uniformity.

Lastly, the processability benefits of dry coating were evaluated during the tableting stage. Two studies were performed: a tabletability assessment at varying compression speeds and a sticking assessment. Compaction trials were conducted with varying drug loads of 10%, 30%, and 60% to compare the dry coating effectiveness of LabRAM and COMIL with the traditional 1 wt.% silica blending approach. The analysis revealed significant impacts on tablet attributes, with the highest tensile strength observed in LabRAM-coated API cases, intermediate in COMIL-coated cases, and the lowest in traditional silica blended formulation tablets. This highlights the critical role of shear in silica dispersion and coating effectiveness. Moreover, both LabRAM and COMIL facilitated high-speed tableting at higher drug loads (30% and 60%), while the silica added cases failed beyond a drug load of 10%. Importantly, the enhanced tablet properties observed in LabRAM and COMIL coated API formulation cases were achieved with significantly lower silica content (ranging from 0.1 wt.% for a 10% drug load to 0.6 wt.% for a 60% drug load), indicating that uniform coating with less silica effectively improved tabletability.

This investigation provides valuable insights into the superiority of the SAC-based approach over the traditional 1 wt.% silica addition method. It also highlights the limitations of conventional metrics in capturing improvements in flow properties of dry coated materials and demonstrates the impact of coating processibility on feedability and tablet attributes. The findings support the benefits of the dry coating process in enhancing tablet processibility at an industrially relevant scale.