Development of Paclitaxel Injection Concentrate for Nanodispersion.

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery Systems
• Nanotechnology

Background:

• Paclitaxel is a crucial chemotherapeutic agent with limited solubility.
• Existing formulations often contain Cremophor EL, which can cause hypersensitivity reactions.
• Development of stable, protein-free paclitaxel formulations is clinically relevant.

Purpose of the Study:

• To develop and characterize a novel paclitaxel injection concentrate for nanodispersion (PICN).
• To evaluate the excipient system, nanodispersion properties, and stability of the PICN formulation.
• To demonstrate PICN as a viable, protein-free alternative to existing paclitaxel formulations.

Main Methods:

• Systematic screening and optimization of excipients including fatty acids, sterols, polymers, and solvents.
• Characterization of nanodispersion particle size, morphology (TEM), crystallinity (DSC, XRD), and phase behavior (SAXS).
• Stability studies under ICH conditions and reconstitution studies in dextrose solution (D5W).

Main Results:

• A synergistic excipient system (sodium cholesterol sulphate, caprylic acid, povidone K12 in PEG 400/ethanol) was identified for PICN.
• PICN reliably formed amorphous, non-crystalline nanoparticles (50-150 nm) with a sponge-like coacervate phase.
• The formulation exhibited excellent stability (24 months) and consistent in-vitro release, with minimal impact from reconstitution.

Conclusions:

• The developed PICN formulation is stable, scalable, and protein-free.
• PICN demonstrates self-assembly of paclitaxel into nanoparticles driven by selected lipids and polymers.
• This novel formulation presents a promising alternative for clinical paclitaxel administration.