PRODUCTION OF ALBENDAZOLE NANOSUSPENSIONS BY HIGH PRESSURE HOMOGENIZA TION USING BILE SAL TS

P. NATALINI; N. CALAMANTE; W. STARKLOFF; M. F. RAZUC; M. V. RAMIREZ RIGO

Rosario

Congreso; 4ta. Reunión Internacional de Ciencias Farmacéuticas; 2016

Albendazole (ABZ) is an antiparasitic agent widely used in medicine. Due to its low oral bioavailability, many strategies were developed to improve drug dissolution rate. 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. However, ABZ formulations containing bile salts have not been reported. 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 and the influence of the number of homogenization cycles on the particle size distribution. 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 suspensions and NSs were determined by laser diffraction and photon correlation spectroscopy, respectively.The median volumetric diameters (D50) of the 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, respectively). ABZ NSs had mean hydrodynamic diameters between 0.45-0.68 μm after10 homogenization cycles, and no significant changes were observed when more cycles were applied. The NSs 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 the application of 10 homogenization cycles at 800 bar is a suitable technique for the development of ABZ NSs.