Impact of the hydrophobic blocks of poloxamers in long-term stability and size of fenbendazole nanocrystals

BEDOGNI, GR; SEREMETA, KP; OKULIK, NB; SALOMON, CJ

CABA

Workshop; Workshop Internacional: Fronteras en Nanobiotecnología III; 2022

Facultad de Farmacia y Bioquímica - UBA

Fenbendazole is a highly hydrophobic antiparasitic drug and, as a consequence, the low aqueous solubility and dissolution rate may compromise its absorption and efficacy. To overcome this drawback, the aim of this work was to apply a nanotechnological approach in order to improve drug solubility and dissolution in aqueous media. Thus, fenbenzadole nanocrystals using poloxamers with 70% of polyoxyethyleneoxide (PEO, hydrophilic fraction), but different concentration of polyoxypropylene (PPO, hydrophobic fraction) were developed. Nanosuspensions were prepared by adding dropwise fenbendazole dissolved in a hydrochloric-acid ethanolic solution over a 0.1% aqueous solution of each poloxamer (P237 and P407, with 2300 g/mol and 4000 g/mol of PPO, respectively). Nanocrystals (P237-NC and P407-NC) were recovered by freeze-drying and a physicochemical characterization was performed. Particle characterization by dynamic light scattering showed a hydrodynamic diameter (Hd) of 185.0 ± 17 nm/372.80 ± 34 nm before/after freeze-drying and polydispersion index (PdI) under 0.501 for P407-NC. Zeta potential (ζ) remained around -31.03 ± 1.47 mV. When P237 was used as stabilizer higher particles with lower negative ζ were obtained, Hd was 339.79 ± 32 nm/438.33 ± 18 nm, before/after freeze-drying, PdI under 0.715 and ζ of -19.37 ± 1.38 mV. After three years of storage at room temperature, an Hd of 378.97 ± 43 nm (PdI= 0.60 ± 0.03) was measured for P407-NC and 609.87 ± 36 nm (PdI= 0.95 ± 0.04) for P237-NC. No changes in ζ were observed. Analysis by differential scanning calorimetry indicated that fenbendazole was in a crystalline state, while FTIR-ATR spectra revealed the characteristic peaks of the raw drug. Release profiles were obtained in HCl pH 1.2 and phosphate buffer pH 7 applying the dialysis membrane method at 37 ± 0.5 °C. Release rate obtained for the nanosuspensions and raw drug showed that statistically significant differences were obtained in HCl (p