Investigating Poloxamer Drug Delivery Systems via Small-Angle Neutron and X-ray Scattering: Effects of Drug Type and Concentration on Structure

In this study, we employed Small-Angle Neutron and X-ray Scattering (SANS/SAXS) to analyze the structural properties of poloxamer-based drug delivery systems. Measurements were conducted using the VSANS-V16 instrument at the Helmholtz-Zentrum Berlin (HZB), Germany. The formulations contained 20% poloxamer (P407) and 0.1%-1% of Nystatin, Prednisolone, Resveratrol, Doxycycline, Rambutan, Mangosteen, Diclofenac, Ketoprofen, Ibuprofen, or Paracetamol in deuterated water (D₂O). Samples were measured under different drug concentrations and temperatures (25 °C, 37 °C, and 40 °C). Given the strong correlation between their thermal properties and molecular structure, a detailed investigation using well-established techniques is essential for advancing new applications. Further measurements explored macrostructure formation, with and without drugs, using the SANS2D instrument at the ISIS Neutron and Muon Source in the UK. These experiments examined P407 concentrations ranging from 6% to 20% in 2% increments at 25 °C. Separate tests were conducted incorporating 0.2% of Ibuprofen, Ketoprofen, or Diclofenac. Small-angle X-ray scattering (SAXS) measurements were performed at the B21 beamline (Diamond Light Source, UK) using a temperature ramp (10 to 80 °C) to analyze phase transitions. Data modeling was performed using a Python-based approach. Scattering intensity as a function of the scattering vector was described as the product of the form factor and the interparticle structure factor within the local-monodisperse approximation. An additional scattering contribution was identified, possibly linked to crystalline macrostructure where micelles organize into a cubic phase. Extracting structural parameters and studying phase transitions in drug carriers can significantly benefit the pharmaceutical industry, providing insights into micellar organization. These insights enable better formulation design, enhancing drug stability, solubility, and bioavailability to advance drug delivery systems.