(703a) Evaluating Different Dry Coating Processes for Preparing Fine-Grade High Functional Microcrystalline Cellulose

Previous studies (1, 2) showed that dry particle coating can be used to develop new excipients through a batch process using LabRAM (a high intensity mixer) and a continuous process using fluid energy mill (FEM). In addition, another device that is continuous in its operation can also be used, called a conical mill or comil (3). Although these processes share the same mechanism of dry coating that small guest particles get coated onto the big host particles via high intensity mechanical forces, there are subtle differences which could mean that the properties of the excipients prepared from these methods would be different from each other. Therefore, this work aims to evaluate the relative effectiveness of different dry coating methods for developing fine grade high functional excipients. In order to achieve a head-to-head comparison, the starting material in all cases was Avicel PH-102 milled down using FEM to ~30 µm size. The milled Avicel PH-102 was dry coated with 1.0 wt% A200 using both LabRAM and Comil. In parallel, Avicel PH-102 was also milled and simultaneously dry coated with 1.0 wt% A200 to obtained dry coated fine excipient of ~30 µm size. The properties of the excipients prepared via three different methods were compared, and the ability to improve the processability of blends with a challenging API (model BCS II drug, Ibuprofen) at 60% drug loading was also investigated. The results show that all the three dry coating techniques allow significant property enhancement of fine grade MCC. Moreover, all the excipients prepared from the three processing methods demonstrated significant processability enhancement as compared to other commercial grade MCC based excipients. In addition, the prepared excipients from FEM showed the best overall performance on improving the properties of Ibuprofen blends and tablets, followed by Comil and then LabRAM. Overall conclusions are: (1) LabRAM processing had the best overall coating quality, achieved through a simple batch process, (2) Comil processing was deemed to be a promising continuous dry coating process but required an intensive pre-blending process, especially for cohesive materials, to achieve good processability, and (3) FEM processing was found to be a most feasible continuous dry coating process for both cohesive and good flowing materials. This study therefore highlights the importance of selecting a robust method for dry particle coating that will deliver the desired functionality in tableting.

1. Chen L, Ding X, He Z, Huang Z, Kunnath KT, Zheng K, et al. Surface engineered excipients: I. improved functional properties of fine grade microcrystalline cellulose. International Journal of Pharmaceutics. 2018;536(1):127-37.
2. Chen L, Ding X, He Z, Fan S, Kunnath KT, Zheng K, et al. Surface engineered excipients: II. Simultaneous milling and dry coating for preparation of fine-grade microcrystalline cellulose with enhanced properties. International Journal of Pharmaceutics. 2018;546(1):125-36.
3. Chattoraj S, Shi L, Sun CC. Profoundly improving flow properties of a cohesive cellulose powder by surface coating with nano‐silica through comilling. Journal of Pharmaceutical Sciences. 2011;100(11):4943-52.