Production of albendazole nanosuspensions by high pressure homogenization using bile salts

STARKLOFF W; RAZUC M; RAMÍREZ RIGO M; NATALINI P; CALAMANTE N

Rosario

Congreso; 4ta Reunión Internacional de Ciencias Farmacéuticas; 2016

Universidad Nacional de Rosario - Universidad Nacional de Córdoba

Albendazole (ABZ) is an antiparasitic agent, widely used in human and veterinary medicine. Due to its low oral bioavailability, many strategies were developed to improve drug dissolution rate. Among others, ABZ nanocrystal production by high pressure homogenization (HPH) is a promising technique to overcome this issue, and a set of excipients were proposed as stabilizers. It was demonstrated that, compared to other surfactants, bile salts enhance drug absorption constant. However, ABZ formulations containing bile salts have not been reported. For this reason, the purpose of this work was to study the performance of taurocholate (STC) and glycocholate (SGC) sodium salts as stabilizers of ABZ nanosuspensions (NSs) prepared by HPH. The effect of the bile salt used and the number of the homogenization cycles on particle size distribution were evaluated. ABZ was dispersed in STC or SGC solutions (1% ABZ, 0.03% bile salt, w/v) using a rotor?stator homogenizer at 30000 rpm and ultrasonic cavitation (10 min each). Pre-homogenized samples were processed by HPH (10, 20, 30, 40 cycles at 800 bar). Particle size distribution of feed suspensions and NSs were determined by laser diffraction and photon correlation spectroscopy, respectively.The median volumetric diameters (D50) of the coarse dispersions were 48 μm and 15 µm when STC or SGC were used as stabilizer, respectively. The pre-homogenization procedure significantly reduced D50 (11.9 and 6.08 μm for ABZ-STC and ABZ-SGC samples, respectively). ABZ NSs had mean hydrodynamic diameters (Z-size) between 0.45-0.68 μm after 10 homogenization cycles, and no significant changes were observed when more cycles were applied. The nanosuspension stabilized with SGC was the most promising one, since it had a Z-size of 0.46 ± 0.01 μm and the lowest polydispertity index (0.26 ± 0.01).The results demonstrated that SGC is a better stabilizer, compared with STC, and that the application of 10 homogenization cycles at 800 bar is a suitable technique for the development of ABZ NSs.