4D study of liquid binder penetration dynamics in pharmaceutical powders using synchrotron X-ray micro computed tomography.

The properties of pharmaceutical powders, and the liquid binder, directly influence the penetration behavior in the wet granulation process of the pharmaceutical industry. Conventional methods encounter challenges in understanding this fast process. In this work, an emerging synchrotron-based X-ray imaging technique (having fast imaging capability) was employed to investigate the internal process from 2D and 3D to real-time (in-situ with ms time intervals) 3D (also considered 4D) perspectives. Two commonly used excipients (lactose monohydrate (LMH) and microcrystalline cellulose (MCC)) were used to make binary mixtures with acetaminophen (APAP) as the active pharmaceutical ingredient (API). Isopropanol and water were employed as liquid binders in the single droplet impact method. Results showed that for most of the mixtures, the porosity increased at higher fractions of APAP. MCC mixtures experienced less agglomeration and more uniform pore distribution than LMH ones, resulting in a faster droplet penetration with isopropanol. Moreover, the imbibition-spreading studies showed that isopropanol penetration in MCC powders followed more unidirectional vertical movement than horizontal spreading. Our results also demonstrated that simultaneous granulation of LMH with water resulted in much slower penetration. This study revealed that synchrotron X-ray imaging can investigate 3D internal pore structures and how they affect the quantitively real-time internal penetration dynamics.