(98b) Using the Conical Screen Mill As a Practical and Effective Dry-Coating Process to Enable Direct Compaction for High Drug Loading Formulations

Direct compaction is the simplest and most preferred process route in the manufacturing of tablets. Unfortunately, direct compaction cannot often be developed without severely restricting drug loading due to the poor flow and compaction properties typical of the active pharmaceutical ingredient (API). Dry-coating processes, which coat API or excipients with glidant (nano-sized silicon dioxide), have been shown effective to improve the manufacturability of formulations containing APIs with poor flowability and tabletability. Accordingly, dry-coating has been considered an enabling technology for direct compaction. Despite the advantages of dry-coating at the lab-scale using a wide variety of equipment such as powder blenders/mixers and mills, manufacturing-scale processes have yet to gain significant acceptance. This may be due to the poor scalability of dry-coating processes or presumably due to the aversion of risk associated with adopting new technology in the pharmaceutical industry.

One particularly attractive dry-coating device which has high relevance to the pharmaceutical industry is the conical screen mill (comill). The comill is a continuous process which is frequently employed in the production of tablets as a screening/de-lumping or particle size reduction process. Several lab-scale studies have shown that the comill is capable of dry-coating, but typically not as effective or efficient as batch processing equipment due to the very short residence time.

As a major novelty, this study makes a simple and easy modification to the comill screen in order to improve the effectiveness and efficiency of the comill used as a dry-coating device. The effect of screen properties and processing conditions are evaluated for a model cohesive material, Avicel PH 105. It is shown that the flowability of Avicel PH 105 can be improved equally as well as a benchmark batch dry-coating device known as the LabRAM (Resodyn Acoustic Mixer). The comill process with the modified screen is applied to a micronized grade of acetaminophen as well as several in-house APIs. The API’s are formulated into 50% drug loading blends which are all shown to have adequate flowability and tabletability. The industry’s familiarity with the comill combined with its improved effectiveness may allow it to be adopted as a dry-coating process in order to enable direct compaction for high drug loading formulations.

AbbVie funded and participated in the study design, research, data collection, analysis and interpretation of data, as well as writing, reviewing, and approving the publication. Maxx Capece, is an AbbVie employees and may own AbbVie stock/options. Arun Jayaraman and Christian Borchardt are former employee of AbbVie and have no conflicts of interest to report.