Exploring Stabilizing Agents to Prevent Crystal Growth or Aggregation in PTX-NCs Generated via Diverse Nanocrystallization Technologies

This study aimed to prepare paclitaxel nanocrystals (PTX-NCs) for the development of a delivery platform for this poorly water-soluble drug. Herein, using biocompatible polymers as stabilizers, paclitaxel (PTX) was formulated as a nanosuspension using two preparation techniques: (I) ultrasonication followed by freeze-drying and (II) melt-based precipitation (MBP) approach. The effectiveness of various stabilizers in inhibiting the crystal growth and agglomeration of PTX-NCs was discussed. Nanosuspensions developed using the MBP method by employing polyethylene glycol (PEG) derivatives offered superior results compared to the ultrasonication method. Among the various polymers, stabilizers such as Pluronic F-68 and myrj 52 were more efficient against particle size enlargement. The optimized formulation containing PTX/PEG/Pluronic F-68/myrj 52 produced re-dispersible particles of about 74 nm with a smooth spherical morphology, which were stable for approximately 8 h in water, indicating good physical stability following reconstitution. The particles obtained after redispersion of MBP-PTX-NCs powder enhanced the dissolution of PTX compared to plain crystals and had superior chemical stability. A 6-month stability test showed no significant changes in drug content or X-ray powder diffraction (XRPD) pattern. These findings highlighted the potential of forming fine particles from MBP method using biocompatible polymers as a promising method for producing drug nanocrystals (NCs) for poorly soluble drugs without expensive and time-consuming freeze-drying steps.