Enhancing drug processibility through dry coating: Comparison at lab and pilot scales

• Published in: International journal of pharmaceutics Vol. 678; p. 125724
• Main Authors: Tripathi, Siddharth, Escotet-Espinoza, M. Sebastian, Tarabokija, James, Klinzing, Gerard, DiNunzio, James, Davé, Rajesh
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 10.06.2025
• Subjects: Chemistry, Pharmaceutical - methods; Comiling; Drug Compounding - methods; Dry coating processibility; Excipients - chemistry; Flowability enhancement; Particle Size; Permeability; Pilot Projects; Powder characterization; Powder feedability; Powders - chemistry; Silicon Dioxide - chemistry; Tabletability; Tablets - chemistry; Technology, Pharmaceutical - methods; Comiling; Powder feedability; Tabletability; Flowability enhancement; Dry coating processibility; Powder characterization
• ISSN: 0378-5173; 1873-3476; 1873-3476
• DOI: 10.1016/j.ijpharm.2025.125724

[Display omitted] •Dry coating with two different silica led to flow enhancements of six fine powders.•Silica amount selection via SAC-based normalization validated as a better option.•Single-pass pilot scale continuous comilling led to one flow regime improvements.•Dry coated powders exhibited significant improvements in feeding and its uniformity.•API-only dry coating yielded better tablet properties at lesser silica in the blend. Dry coating fine pharmaceutical powders with nano-silica has been shown to enhance their bulk properties and their blend processability at lab-scale, potentially facilitating tablet manufacturing. This study critically investigates key aspects of dry coating from industrial applicability perspective: (1) evaluating the selection of silica amount based on the host particle surface area coverage (SAC) against the industry standard 1 wt% addition, (2) assessing the feasibility of continuous dry coating using a pilot-scale conical screen mill (comil-U10) compared to the lab-scale batch high-intensity vibratory mixer (HIVM), and (3) investigating downstream processing improvements from dry coating via feedability and tabletability studies. Results from six different pharmaceutical powders (d50 ∼ 3–35 μm) demonstrated that SAC-based silica wt.% selection outperformed 1 wt% silica for bulk properties enhancements. Multi-faceted characterization revealed that FFC was the most reliable amongst Hausner’s ratio, compressibility, and permeability tests. Three selected materials (d50 ∼ 16–26 μm) for comil processing showed remarkable one-flow category improvement, though two finer materials fell short of the HIVM performance. The dry coated materials demonstrated superior feed rate stability, demonstrating reduced flow variability, attributed to enhanced flowability and lower compressibility. Tablets of formulations containing dry-coated API using either comil or HIVM outperformed formulations with blended silica at three drug loads, 10 %, 30 %, and 60 %, likely due to better silica dispersion. These outcomes demonstrate the benefits of potentially scalable comil-based dry coating to continuous manufacturing of tableting, potentially eliminating the need for granulation.