[Correlation study on structure, surface free energy, and key direct compression properties of co-spray drying...

This study investigated the effects of different modifiers on the structural characteristics, surface free energy, and key direct compression properties of co-spray drying composite particles, and it established the correlations among particle structure, surface free energy, and direct compression properties. Andrographis Herba extract concentrate was selected as the model drug, and silica(SiO_2), hydroxypropyl-β-cyclodextrin(HPCD), hydroxypropyl cellulose(HPC), and cross-linked polyvinylpyrrolidone(PVPP) were selected as modifiers. Composite particles were prepared by using co-spray drying technology. The particle structure, surface free energy, and direct compression properties of composite particles were systematically characterized. The results show that, compared with unmodified particles, composite particles exhibit significantly improved roundness and surface smoothness; the median particle size(d_(0.5)) of composite particles increases by 7.2%-49.1%, and roundness approaches an ideal spherical morphology. Surface free energy and polarity index of composite particles increase by 0.9%-29.9%, while cohesion work increases by 0.9%-11.7%; Carr's index(CI) and Hausner ratio(HR) of composite particles decrease by 7.3%-26.4% and 7.3%-20.4%, respectively; the angle of repose(AR) of composite particles decreases by 0.4°-6.8°, indicating significantly enhanced powder flowability of composite particles. Tablet tensile strength(TS) of composite particles increases by 20.8%-185.5%, while the disintegration time of composite particles is shortened by 2.2%-24.4%. Pearson correlation analysis reveals that surface free energy is positively correlated with roundness, but negatively correlated with uniformity, cohesiveness, resilience, and red-green chroma(a~*). The dispersive component is positively correlated with a~*, but negatively correlated with particle size distribution(Span) and roundness. The polar component is positively correlated with roundness, but negatively correlated with uniformity, cohesiveness, and a~*. The polarity index is positively correlated with roundness, but negatively correlated with a~*. Cohesion work is positively correlated with roundness, but negatively correlated with uniformity, cohesiveness, resilience, and a~*. Glass transition temperature(T_g) is positively correlated with d_(0.5), specific surface area, and roundness, but negatively correlated with Span. CI and HR are positively correlated with T_g, but negatively correlated with surface free energy and cohesion work. AR is positively correlated with surface free energy, polar component, polarity index, and cohesion work, while negatively correlated with the dispersive component. TS is positively correlated with the dispersive component, but negatively correlated with the polar component and polarity index. Disintegration time of direct compression tablets is negatively correlated with T_g. This study elucidates the intrinsic correlation among structure, surface free energy, and key direct compression properties of co-spray drying composite particles, providing a theoretical basis for the optimization and development of direct compression processes for TCM powders.