Tailored Sugar-Mediated Porous Particle Structures for Improved Dispersion of Drug Nanoparticles in Spray-Freeze-Drying.

We fabricated porous particles incorporating sugars (mannitol, sucrose, or dextran) and fenofibrate nanoparticles (FNPs) by using spray-freeze-drying (SFD). The type of sugar significantly influenced the pore architecture of the resulting SFD particles. Rapid freezing of droplets containing dextran produced ice encapsulation within a dextran matrix, forming porous dextran particles. In the presence of FNPs, the particle size (approximately 4 µm) and pore volume (0.3 cm3/g) of SFD dextran were barely affected. In contrast, SFD particles derived from mannitol and sucrose exhibited denser structures with a lower pore volume than dextran. SFD mannitol incorporating FNPs produced porous structures. FNPs containing surfactant and polymer, which reduced surface tension and increased viscosity, promoted the formation of small droplets with a polymeric structure and porous particles with a relatively sharp size distribution with a median around 5 µm. FNPs were uniformly distributed in SFD dextran, which featured large pore structures, whereas in SFD mannitol, the Raman signal of FNPs was more broadly distributed across the powder samples. Both morphologies contributed to enhancing the FNP dispersibility within a redispersed suspension of SFD particles. FNPs in SFD mannitol and dextran matrices maintained their particle size distribution from before SFD, showing no aggregation upon redispersion. Dextran formed a highly porous network irrespective of the presence of FNPs, whereas mannitol tended to alter the particle attributes upon FNP inclusion. In conclusion, SFD particles derived from dextran and mannitol might help to increase FNP dispersibility by increasing the formation of porous architectures.

Improved water dispersibility and photostability in folic acid nanoparticles with transglycosylated naringin using combined processes of wet-milling and freeze-drying.

We successfully prepared folic acid (FA) nanoparticles with excellent dispersibility and photostability using a combination of bead milling and freeze-drying with transglycosylated naringin (Naringin-G), a newly developed transglycosylated food additive. Poly-vinyl pyrrolidon (PVP) was used for comparison with Naringin-G. Water dispersibility and photostability of the freeze-dried formulations were assessed. The dispersibility and physicochemical properties of nanoparticle formulations were evaluated using dynamic light scattering, powder X-ray diffraction (PXRD), and small-angle X-ray scattering (SAXS). Results indicated that the median particle size of FA in the slurry bead milled with Naringin-G decreased notably with time and fell below 100 nm after milling for 300 min. Further, FA nanoparticles with Naringin-G were stable without aggregation following re-dispersion of freeze-dried FA formulations in water. Contrarily, the addition of PVP did not prevent the aggregation of FA nanoparticles following re-dispersion of freeze-dried FA formulations. Solid structures of freeze-dried FA formulations with Naringin-G or PVP were assessed using PXRD and SAXS. PXRD patterns of all freeze-dried formulations highlighted broadening and weakening of peaks, indicating a decrease in FA crystallinity following bead milling, regardless of the additive concentration of Naringin-G and PVP. The scattering intensity profiles of FA formulations with PVP dramatically decreased after milling, whereas FA formulations with Naringin-G did not exhibit changes in SAXS patterns. FA formulations with Naringin-G registered faster enhancement in release rate than PVP in pH 1.2 buffer solutions. The release rate of freeze-dried FA formulation with Naringin-G exhibited at least five-fold enhancement when compared to untreated FA. FA formulation with Naringin-G was stable to photodegradation under fluorescent light. Naringin-G prevented photodegradation of FA due to its antioxidant effect and scavenged radicals. These findings indicated that freeze-dried FA formulation with Naringin-G can improve its water-dispersibility and photodegradation due to the effectiveness of Naringin-G as a dispersant and cryoprotectant.

Inhibition of Photodegradation of Highly Dispersed Folic Acid Nanoparticles by the Antioxidant Effect of Transglycosylated Rutin.

We developed highly dispersible and photostable nanoparticles of vitamin, folic acid (FA). FA was wet bead milled with milling and dispersing adjuvants and transglycosylated compounds such as α-glucosyl hesperidin (Hesperidin-G) and rutin (Rutin-G), which solubilized FA. The milled slurries of FA particles with transglycosylated compounds consisted of nanosized particles with a median diameter of <100 nm. The lyophilized formulations of these slurries retained their nanometer size after resuspension in water with no aggregation. The apparent solubility of FA in these formulations was 100-fold higher than that of untreated FA. The solubilizing effect of Rutin-G may affect the particle size reduction and dispersibility of FA. The photostability results showed that the strong antioxidant activity of Rutin-G substantially increased the photostability of FA solution. On the basis of these results, bead milling of FA with Rutin-G is a promising technique for developing highly dispersible, photostable nanoparticle FA formulations.