Case Study 603 Wet-granulation behaviour I
This case study, authored by Dan Burnett of Surface Measurement Systems Ltd., investigates how the work of adhesion between model drugs (acetaminophen and ibuprofen) and common binders (hydroxypropylcellulose – HPC, hydroxypropyl‑methylcellulose – HPMC, and polyvinylpyrrolidone – PVP) can be predicted from surface‑energy measurements obtained via Inverse Gas Chromatography (SMS‑iGC SEA 2000). The theoretical framework links surface energy components (dispersive and specific, expressed as γd, γ+, γ−) to the work of adhesion (Wadh) using classic thermodynamic equations. Materials were characterized by measuring dispersive contributions with a series of alkanes and specific contributions with toluene and chloroform under infinite‑dilution conditions. Wet‑granulation was performed with 4 % binder solutions, followed by drying, milling, and tabletting at 25 kN. Tablet mechanical properties (crushing strength, friability) were measured. Results show that HPC provides the highest Wadh for both drugs, followed by HPMC and PVP, and that higher Wadh correlates with higher tablet hardness and lower friability. The ratio Wadh/Wcoh (work of adhesion to work of cohesion) is identified as a robust predictor of tablet performance, illustrating that thermodynamic compatibility between drug and binder is essential for successful wet‑granulation. The study concludes that IGC‑derived surface‑energy data can be used to forecast drug‑excipient interactions and guide formulation design.
Topics
Thermodynamic Basis for Predicting Drug‑Binder Adhesion
Presentation of the surface‑energy theory, including dispersive and specific components, and the equations linking them to work of adhesion (Wadh) and work of cohesion (Wcoh).