(198i) Investigating Role of Surfactants in the Wetting Behavior of Pharmaceuticals and the Resulting Impact on Dissolution Performance

Poor API wettability is a recurring challenge in formulation development. Even in APIs with high solubility (thermodynamic factor), presence of hydrophobic facets in API crystals can lead to poor wettability, negatively impacting disintegration and dissolution rate (kinetic factor). This is particularly exacerbated in highly sought-after tablets with high drug-loading. Surfactants are routinely incorporated in tablets to improve dissolution behavior as they are known to decrease the interfacial tension between drug particles and the dissolution media. While the choice of type/levels of surfactants can greatly impact the wettability and ultimate dissolution performance of the drug product, this selection is often made on a trial-and-error basis, which is inefficient in terms of resources and formulation development timeline. Hence, systematic study on the impact of surfactants on wettability and dissolution is crucial to delivering new drug products to market as quickly and efficiently as possible.

Herein, we investigate role of surfactants in wettability of pharmaceutical tablets and its impact on disintegration time and dissolution of two poorly wettable APIs. Specifically, we systematically modulate wettability of powder blends and tablets by incorporating different surfactants at varying concentrations. The wettability of tablets is quantified by determining the contact angle of a sessile droplet interacting with the surface of powder blends and tablets. By utilizing both experimental methods and molecular dynamics (MD) simulation, we investigate the impact of a) molecular structure of surfactants, b) their levels, as well as c) their interactions with API, on the wettability and dissolution rate of the API. Initial results have indicated substantial impact of surfactant molecular structure and levels on the wettability and dissolution performance of the APIs which is further investigated by using MD simulation. We anticipate that the results from this study will provide significant insights on the relationship between surfactants, wettability, and crucial tablet properties such as disintegration and dissolution. Moreover, the study will provide guidance on systematically incorporating surfactants in formulations ultimately aiding efficient formulation development of poorly wettable APIs. Furthermore, learnings from the study will be leveraged in other unit operations such as film coating, where tablet surface wettability might dictate resulting critical quality attributes.