J Pharm Sci. 2026 Oct 28:104570. doi: 10.1016/j.xphs.2026.104570. Online ahead of print.
ABSTRACT
Sticking of active pharmaceutical ingredients (APIs) to punches and dies remains a significant challenge in direct compression, particularly for highly adhesive compounds such as trazodone hydrochloride. This study investigated influence of lubricant type, premix design, and mixing sequence on lubrication efficiency and sticking mitigation. Binary mixtures containing trazodone hydrochloride and either magnesium stearate or amorphous porous silica (Syloid) were compared with ternary systems combining both excipients. Magnesium stearate provided effective boundary lubrication and markedly reduced sticking propensity, whereas Syloid alone showed poor lubrication efficiency and in some cases increased sticking behavior. Conversely, ternary systems exhibited strong dependence on the order of component incorporation. SEM/EDS analysis revealed Syloid can preferentially occupy API surfaces when introduced during early mixing stages, limiting access of magnesium stearate to critical interfacial regions and reducing lubrication efficiency. Conversely, premixing strategies favoring early adsorption of magnesium stearate promoted formation of effective lubrication layer and resulted in synergistically improved compaction performance. Surface etching experiments indicated pressure-dependent redistribution of magnesium stearate during compaction, consistent with its pronounced plastic deformability. Findings demonstrate lubrication efficiency is determined not only by lubricant selection but also by sequence-dependent microstructural organization established during premixing, highlighting premix design as a critical parameter for mitigating sticking.
PMID:42950988 | DOI:10.1016/j.xphs.2026.104570
Share Evidence Blueprint
Save to Google Notes
Search Google Scholar
Save as PDF
⭐ My Revision List
