Quantification of Excipients Proportion Effects on the Wettability of Formulations with a High-Dose of Hydrophobic Drug

Powder wetting and liquid penetration dynamics are critical in wet granulation, particularly for formulations containing poorly wettable drugs such as ibuprofen. So that, it is necessary to understand water-powder interactions if an optimized granulation process is required. In the present study we investigate the capillary wetting of a simplified model formulation composed of 60wt% of ibuprofen (a hydrophobic drug), 3wt% of polyvinylpyrrolidone (a binder) and different ratios of two common excipients, lactose and microcrystalline cellulose (MCC). In particular, we focus on the effects produced by three specific ratios of lactose to MCC, 50:50, 70:30, and 90:10.In order to quantify the effects of lactose:MCC ratios, drop penetration experiments using water and polydimethylsiloxane were performed on porous powder beds. The results are analyzed through a previously developed capillary imbibition model that was adapted to address the specific complexities introduced by the formulations. The main modification is the definition of the strength of interaction parameter, β, which captures microscopic wetting effects and structural changes (e.g., swelling). Thereby, our model gives microscopic information by using macroscopic measurements without requiring detailed knowledge of internal porous properties.It was observed that water failed to penetrate pure ibuprofen, whereas the addition of excipients enabled liquid penetration. The parameter β showed that MCC content plays an important role in penetration dynamics, with increasing MCC proportions leading to higher water penetration rates. The same trend was qualitatively observed in highly compacted tablets, but penetration times are considerably enlarged so, dissolution effects cannot be discharged.The proposed capillary imbibition model and the parameter β effectively characterize liquid-powder interactions using simple macroscopic experiments. This approach enables penetration times to be tuned to the residence times of granulation process, providing a cost-effective tool for formulation design and optimization. Consequently, it can significantly reduce the need for the extensive trial-and-error studies that are traditionally used during formulation screening.