Development of albendazole nanocrystals through Microsphere-Assisted Milling

Rosario

Congreso; 7 MA REUNIÓN INTERNACIONAL DE CIENCIAS FARMACÉUTICAS; 2023

Albendazole (ABZ) is a key antiparasitic agent in the treatment of many neglected tropical parasitic infections. However, despite being considered an essential medication by the World Health Organization, this drug has extremely low aqueous solubility. As a result, ABZ is classified as Class II in the Biopharmaceutical Classification System. Pharmaceutical sciences employ a variety of strategies to overcome the problems associated with poorly soluble active ingredients, and one alternative of particular interest is the application of nanotechnology. In this context, the aim of the present study was to synthesize and characterize ABZ Nanocrystals using the Nanomilling Assisted by Microspheres (NAM) technique with Poloxamer® 407 (P407) and Maltodextrin (MD) as milling stabilizer agents. a laboratory-scale NanoDisp® mill (NanoDisp®, Córdoba, Argentina) was used to prepare nanosuspensions utilizing a reference method described in the literature. Initially, nanosuspensions with different proportions of the drug and milling stabilizer agents were prepared: ABZ:MD in a 50:50 %w/w and 75:25 %w/w ratio, and ABZ:P407:MD in a 50:25:25 %w/w and 75:12.5:12.5 %w/w ratio. The optimal nanosuspension was found to be composed of ABZ:P407:MD in a 75:12.5:12.5 %w/w ratio. It was then lyophilized with a yield of 94.4%, suggesting that there were no significant material losses during milling. The resulting Nanocrystals exhibited a particle size of (448 ± 8) nm, a polydispersity index of 0.30 ± 0.03, which was consistent with monodisperse samples, and a zeta potential of (-26.9 ± 0.4) mV. Furthermore, the developed Nanocrystals were characterized using Powder X-ray Diffraction (PXRD), Fourier Transform Infrared Spectroscopy (FT-IR), Scanning Electron Microscopy (SEM), and Energy-Dispersive X-ray Spectroscopy (EDS). The biopharmaceutical properties were also studied through Solubility and in vitro Dissolution studies. The FT-IR and PXRD results demonstrated that the ABZ structure was not altered during the milling process, indicating that the stabilizers are working as intended without causing the formation of a new solid phase through drug-stabilizer interaction or polymorphic transformation. Additionally, milling process was successful in dispersing ABZ in the sample since SEM and EDS studies revealed a morphology distinct from that of ABZ and a homogeneous distribution of the drug, In addition, the Nanocrystals also showed significant improvements in the unfavorable properties of ABZ, such as solubility and dissolution percentage. In particular, the solubility was X times higher than ABZ free, and the dissolution percentage at 2 hours was 15 times higher than it was for the free drug. In conclusion, it was confirmed that the used synthesis technique is a rapid, simple, reproducible, cost-effective, and highly scalable tool. As a result, NAM is a useful technique for developing innovative formulations for the treatment of neglected diseases.