Modulating Sticking Propensity of Pharmaceuticals Through Excipient Selection in a Direct Compression Tablet...

Prior research has shown that punch sticking during tablet compression affects production efficiency and product quality. Established knowledge includes the role of excipient properties in tablet mechanical strength and flow behavior. However, the specific relationship between bonding interactions within the formulation and sticking propensity remains unclear. No prior work had resolved how API-excipient interactions influence sticking severity. This gap motivated a focused investigation into how excipient matrices modulate sticking behavior. Existing studies have not directly compared sticking trends across multiple excipient types and APIs. The need arises to clarify whether mechanical strength or bonding strength is the dominant factor in mitigating sticking. This paper's contribution lies in systematically evaluating excipient effects on both API-API and API-excipient bonding. The study bridges a gap in understanding how excipient choice can be leveraged to control sticking in direct compression.

The aim of this study was to evaluate how excipient matrix influences punch sticking propensity of active pharmaceutical ingredients. The specific problem addressed is the lack of clarity on whether API-API or API-excipient bonding interactions dominate in determining sticking behavior. The motivation stems from the need to optimize excipient selection for reduced sticking in tablet production. The study focused on two APIs—celecoxib and ibuprofen—within five distinct excipient matrices. The goal was to determine if excipient-induced mechanical strength correlates with reduced sticking. The research sought to clarify whether higher bonding strength or higher mechanical strength mitigates sticking. The study also aimed to compare sticking trends across different excipient types. This approach provides actionable insights for excipient selection in direct compression tablet formulations.

The study used a compaction simulator with a removable punch tip to assess sticking kinetics. Formulations contained 20% of either celecoxib or ibuprofen in five excipient matrices: Avicel PH102, Avicel PH105(n), K15 M, and S3P1. Sticking was measured gravimetrically after every 10 compressions up to 50. The excipient matrices varied in composition and surface modification, including dry-coated silica. The punch tip was cleaned and reweighed after each set of compressions to quantify material transfer. The study compared sticking propensity across APIs and excipient types. The bonding interactions between API-API (F2) and API-excipient (F3) were analyzed. The method allowed direct comparison of sticking severity under identical compaction conditions.

Celecoxib showed higher API-API bonding (F2) than ibuprofen under identical conditions. Celecoxib also exhibited greater sticking in the same excipient matrix. Sticking propensity increased in the order: PH105(n) < PH102 < K15 M < S3P1 for both APIs. This order was opposite to the API-excipient bonding (F3) strength ranking. Higher bonding strength in the formulation correlated with lower sticking severity. The results suggest that formulation bonding strength is more critical than mechanical strength in mitigating sticking. The 3:1 starch-Avicel mixture (S3P1) showed the highest sticking propensity. The dry-coated Avicel PH105(n) exhibited the lowest sticking for both APIs.

The authors propose that excipient choice influences punch sticking through formulation bonding strength. Greater API-excipient interactions (F3) reduce sticking severity in direct compression. The study confirms that higher bonding strength correlates with lower sticking propensity. The results support the use of excipients that enhance formulation bonding to mitigate sticking. The observed order of sticking propensity aligns with the bonding strength rankings. The findings suggest that excipient selection should prioritize bonding interactions over mechanical strength. The authors conclude that judicious excipient use can reduce sticking in formulations prone to this issue. The study provides evidence that excipient matrices can be strategically chosen to control sticking behavior.