Characterization of physico-chemical properties and pharmaceutical performance of sucrose co-freeze–dried solid nanoparticulate powders of the anti-HIV agent loviride prepared by media milling

In order to improve the dissolution and absorption properties of loviride, a poorly soluble antiviral agent, sucrose co-freeze–dried nanopowders were prepared, characterized and evaluated. Tween 80/poloxamer 188-stabilized nanosuspensions were produced on a laboratory scale using media milling. The milling process was monitored by dynamic light scattering (DLS) and resulted in particles with a mean size of 264 ± 14 nm and a distribution width of 59 ± 6 nm after 4 h of milling. Co-freeze–drying of the nanosuspensions with sucrose had an inhibiting effect on nanoparticle agglomeration and yielded solid “nanopowders” that were resuspendable and homogeneous with respect to loviride content. X-ray powder diffraction (XRPD) confirmed the presence of small loviride crystallites and indicated that sucrose and poloxamer 188 were crystalline. Differential scanning calorimetry (DSC) showed melting peaks of poloxamer 188, sucrose and loviride. Time-resolved XRPD indicated that sucrose crystallization was complete within 24 h of storage. Scanning electron microscopy (SEM) suggested the formation of sheet-like matrix structures. The dissolution rate of loviride from the nanopowders was excellent. A Caco-2 experiment on the nanopowder showed a significantly higher cumulative amount transported after 120 min (1.59 ± 0.02 μg) compared to the physical mixture (0.93 ± 0.01 μg) and the untreated loviride (0.74 ± 0.03 μg).