INVESTIGATION OF THE COCRYSTALLIZATION AND COAMORPHIZATION OF ALBENDAZOLE WITH TRYPTOPHAN

MARCOS VALDES M.; BRUNO F.; FANDIÑO O.; SPERANDEO N.

Rosario

Congreso; 4° Reunión Internacional de Ciencias Farmaceuticas (RICiFa); 2016

IntroductionPharmaceutical cocrystallization and coamorphization are a relatively recent technology, which offers an alternative platform to improve the physicochemical properties of active pharmaceutical ingredients (APIs), such as the melting point, solubility, stability, and dissolution rate. The improved properties of these systems, were attributed to molecular interactions between the drug and its coformers.The aim of this study was to prepare systems binary of albendazole (ABZ), an antiparasitic to Class II of the Biopharmaceutical Classification System, to enhance aqueous solubility and obtain a new therapeutic alternatives for the treatment of parasitic diseases.Materials and MethodsAlbendazole (purity >99.5%) and Arginine, Tryptophan (Sigma-Aldrich) were mixed in 1:1 molar ratio and subjected to Liquid Assisted Grinding (LAG)3 for 20 minutes, Liquid Assisted Sonication (LAS)3 for 30 minutes or to freeze-drying. Ethyl acetate (AEt) and methanol (MeOH) were purchased from commercial sources and were of analytical reagent grade. The obtained samples were analyzed by Hot Stage Microscopy (HSM, Leitz, Wetzlar), Powder X-ray Diffraction (PXRD, Bruker D8 Advance, Cu-anode) and Fourier Transform Infrared (FTIR, Nicolet-Avatar 360).Results and discussionTen ABZ-coformer 1:1, 1:2 and 2:1 samples were prepared by LAG, LAS and freeze-drying methods. The results of the screening are summarized in Table 1. According to HSM, the samples 1, 2, 4, 6, 7 and 8 showed melting point (mp) similar to ABZ, within to the experimental error of the Kofler method, discarding the formation of coamorphous. The samples 5 (ABZ-ARG 1:1) and 9 (ABZ-TRP 1:1) had different mp´s, which fell between those of ABZ and the ARG/TRP, and this suggests the formation of cocrystals or coamorphous. Therefore, two potential hits were identified in the HSM screening and analysed by DRIFT and PXRD. The DRIFT spectra of the samples 5 and 9 showed showed a generalized broadening in the characteristic absorption bands of ABZ-ARG and ABZ-TRP respectively, and the shifts of signals near 1600-1700 cm-1 indicating that ABZ-ARG 1: 1 presents changes in the vibrational modes with respect to the starting materials. Furthermore, in the patterns corresponding to PDRX ABZ-ARG 1:1 and ABZ-TRP 1:1 the disappearance of characteristic reflection planes of ABZ and partial amorphization of the samples was observed. ConclusionsThe coamorphization of ABZ with ARG and TRP was tested using LAG, LAS and freeze-drying methods and two solvents. FTIR and PXRD spectra of the remaining samples showed difference with those of the starting compounds, revealing that ABZ interact with ARG and TRP under the conditions tested. This study demonstrates that the freeze-drying of ABZ-ARG 1:1 and ABZ-TRP 1:1 produces a higher degree of crystalline disorder regarding their precursors, leading to a partially amorphous binary system.