Investigating a Soluble Pharmaceutical Salt: Albendazole Hydrochloride

Abstract

Albendazole is an effective antihelmintic drug, which has an unpredictable therapeutic response due to its low solubility in biological fluids that limits its oral absorption. In an attempt to improve solubility, albendazole hydrochloride, a soluble pharmaceutical salt, was obtained and characterized by X-ray diffraction together with magic angle spinning solid-state nuclear magnetic resonance spectroscopy, Raman and Fourier transform infrared spectroscopies, thermal analysis, energy-dispersive X-ray spectroscopy, and scanning electron microscopy. These studies revealed that the crystalline habit of albendazole hydrochloride is different from that of the albendazole solid forms previously reported. The full structure was elucidated by performing single-crystal X-ray diffraction. The characterization studies showed the participation of the carbamate moiety in the salt formation. In addition, the solubility studies showed a significant increase in the solubility with respect to forms I and II of albendazole. In conclusion, our results indicate that albendazole hydrochloride can be an auspicious salt to be used as a new product in an attempt to counteract unfavorable pharmaceutical properties.

Amino–Imino Tautomerism in the Salt Formation of Albendazole: Hydrobromide and Nitrate Salts

“…Regardless of which ABZ tautomer is formed from the hydrolysis process, its precipitation is expected due to the poor aqueous solubility of both desmotropic forms. According to the solubility value found for pure ABZ (0.0029 mg mL –1 ), it agrees with the assumption that ABZ form I (amine tautomer) predominates in the dissolution medium, since ABZ form II (imine tautomer) is more soluble than form I. , These findings are consistent with the results from PXRD and DSC analyses, which indicated that the ABZ commercial form used as the starting material is composed of the aminic tautomer (form I).…”

“…Understanding the relative tautomeric stability and the most favorable path for protonation of each tautomer guided the screening of the solid form for the ABZ case, resulting in three pharmaceutical salts: namely, ABZ HCl, ABZ HBr, and ABZ HNO 3 . During the course of this investigation, the crystal structure of ABZ HCl was reported by another group, 27 in which solid-state and solubility improvement relations have been explored. A structural description was obtained, and a physical−chemical characterization of these salts is depicted below.…”

“…The IR spectra provide crucial information about vibrational modes in a molecule and are sensitive to the structure, molecular conformations, and environment of the API . ABZ exhibits IR stretching frequencies at 3340 cm –1 (amide and imidazole NH stretches), 1710 cm –1 (carbamate CO stretch), 1633 and 1623 cm –1 (imidazole C–N stretches and N–H bendings), and 1358 and 1095 cm –1 (ester C–O–C and C–S stretches). , Some of these functional groups showed significant changes in their vibrational patterns on salt formation. The FT-IR spectra of ABZ and its salts are presented in Figure S2.…”

“…20 Also, it is a drug that exhibits poor flow properties and low compression ability. 21,22 Because of this unfavorable pharmaceutical profile, several technologies have been employed to attempt to solve the drawbacks, which include solid dispersions, 23 microencapsulation, 24 cyclodextrin complexation, 25 cocrystallization and salt formation, 26,27 and spherical agglomeration. 28 The compound is considered an important representative of the imidazole drugs.…”

“…ABZ is a class II drug according to the biopharmaceutical classification systems (BCS), as it is practically insoluble in water (0.0228 mg mL –1 at 25 °C) and is poorly absorbed in the gastrointestinal system . Also, it is a drug that exhibits poor flow properties and low compression ability. , Because of this unfavorable pharmaceutical profile, several technologies have been employed to attempt to solve the drawbacks, which include solid dispersions, microencapsulation, cyclodextrin complexation, cocrystallization and salt formation, , and spherical agglomeration . The compound is considered an important representative of the imidazole drugs.…”