Redispersible triclabendazole nanocrystals with enhanced dissolution and in vitro mucin interaction

Fascioliasis is a neglected tropical disease caused by the parasitic flatworms Fasciola hepatica and Fasciola gigantica. Triclabendazole (TCBZ) is the first-line treatment; however, its poor aqueous solubility and high lipophilicity limit its dissolution in gastrointestinal fluids, which may compromise oral performance. TCBZ can be considered a BCS Class II or BCS II-like compound, since its biopharmaceutical behavior is mainly limited by low aqueous solubility and dissolution rate. In this study, TCBZ nanocrystals (TCBZ-NCs) were produced by microsphere-assisted nanomilling and subsequently converted into a redispersible powder by spray drying. The resulting formulation displayed an average hydrodynamic diameter of approximately 355 nm after redispersion, a polydispersity index of approximately 0.3, a zeta potential of approximately - 24 mV, and colloidal stability for up to 90 days at room temperature. SEM and STEM analyses supported the formation of nanosized particles, while FTIR and XRPD analyses indicated no detectable chemical modification and preservation of the crystalline state after processing. TCBZ-NCs exhibited markedly improved dissolution compared with raw TCBZ under acidic non-sink and sink conditions, and retained a clear advantage in phosphate buffer at pH 6.8. In addition, mucin interaction studies and in vitro detachment-force measurements using hydrated model surfaces suggested in vitro mucin-interaction potential. Overall, these results support TCBZ-NCs as a high-drug-load crystalline formulation strategy for improving the dissolution behavior of TCBZ. Further studies using biorelevant dissolution media, cellular, ex vivo, and in vivo models are required to determine whether these in vitro findings translate into improved oral absorption or therapeutic performance.