Improving the Solubility, Stability, and Bioavailability of Albendazole through Synthetic Salts

• Published in: Molecules (Basel, Switzerland) Switzerland), 2024-08, Vol.29 (15), p.3571
• Main Authors: Yan, Haiying, Zhong, Xueping, Liu, Yao
• Format: Article
• Language: English
• Subjects: Adsorption; Albendazole; Albendazole - administration & dosage; Albendazole - chemistry; Albendazole - pharmacokinetics; Amino acids; Animals; Bioavailability; Biological Availability; Calorimetry, Differential Scanning; Cancer; Drug approval; Drug Stability; FDA approval; Fourier transforms; Humidity; Investigations; NMR; Nuclear magnetic resonance; oral bioavailability; Parasitic diseases; Pharmaceutical industry; Raw materials; salt; Salts - chemistry; Scanning electron microscopy; solid-state properties; Solubility; Spectroscopy, Fourier Transform Infrared; Spectrum analysis; stability; Water; X-Ray Diffraction
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules29153571

Albendazole (ABZ) is a highly effective yet poorly water-soluble antiparasitic drug known to form salts (ABZ-FMA, ABZ-DTA, and ABZ-HCl) with fumaric acid (FMA), D-tartaric acid (DTA), and hydrochloric acid (HCl). This research utilized a range of analytical techniques, including Fourier transform infrared spectroscopy (FT-IR), nuclear magnetic resonance hydrogen spectroscopy ( H NMR), powder X-ray diffraction (PXRD), dynamic vapor sorption (DVS), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), and scanning electron microscopy (SEM), to validate and characterize the solid-state properties of these drug salts. This study also assessed the solubility and intrinsic dissolution rate (IDR) of these salts under different pH conditions compared to the active pharmaceutical ingredient (API) and conducted stability studies. Moreover, the in vivo pharmacokinetic performance of ABZ salt was evaluated. The results of this study reveal that the new solid form of ABZ is primarily associated with amino acid esters and benzimidazole groups, forming intermolecular interactions. All three ABZ salts significantly improved the solubility and dissolution rate of ABZ, with ABZ-HCl demonstrating the optimal performance. Importantly, the drug salt exhibited robust physical stability when exposed to adverse conditions, including strong light irradiation (4500 ± 500 lux), high humidity (92.5 ± 5% relative humidity), elevated temperatures (50 ± 2 °C), and accelerated test conditions (40 °C/75 ± 5% relative humidity). Lastly, the in vivo pharmacokinetic analysis demonstrated that ABZ salt led to a substantial increase in AUC and C compared to ABZ. This elevation in solubility in aqueous solvents signifies that ABZ salt exhibits characteristics that can enhance oral bioavailability and pharmacokinetics. These findings provide potential solutions for the development of more effective and innovative drug formulations.