Albendazole solid dispersions prepared using PEG6000 and Poloxamer188: formulation, characterization and in vivo evaluation

Pharm Dev Technol. 2020 Nov;25(9):1043-1052. doi: 10.1080/10837450.2020.1783553. Epub 2020 Jul 3.

Abstract

This study aimed to optimize the preparation process of albendazole (ABZ) solid dispersion (SD) and enhance its dissolution rate and oral bioavailability in dogs. The ABZ-SD formulations were prepared by a fusion method with ABZ and polyethylene glycol 6000 (PEG 6000), poloxamer 188 (P 188) polymers at various weight ratios or the combination of PEG 6000&P 188. The characterizations of the optimal formulations were performed by scanning electron microscopy (SEM), powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy (FTIR), in vitro dissolution test and molecular docking. The in vivo pharmacokinetic study was conducted in beagle dogs. As a result, ABZ solid dispersion based on PEG 6000&P 188 (1:2) was successfully prepared. The ABZ-SD formulation could significantly improve the apparent solubility and dissolution rate of ABZ compared with commercial tablets. Furthermore, the water solubility of ABZ-SD was improved mainly based on hydrogen bond association. Besides, at an oral dosage of 15 mg/kg ABZ, the SDs had higher Cmax values and areas under the curve (AUCs) compared to those of commercial ABZ tablets. Preparation of ABZ-loaded SDs by PEG 6000&P 188 is a promising strategy to improve the oral bioavailability of ABZ.

Keywords: Albendazole; dissolution; molecular docking; oral bioavailability; solid dispersion.

MeSH terms

  • Albendazole / chemistry*
  • Albendazole / pharmacokinetics
  • Animals
  • Calorimetry, Differential Scanning / methods
  • Chemistry, Pharmaceutical / methods
  • Dogs
  • Male
  • Molecular Docking Simulation / methods
  • Poloxamer / chemistry*
  • Polyethylene Glycols / chemistry
  • Polymers / chemistry
  • Powders / chemistry
  • Powders / pharmacokinetics
  • Solubility / drug effects
  • Spectroscopy, Fourier Transform Infrared / methods
  • Tablets / chemistry
  • Tablets / pharmacokinetics
  • X-Ray Diffraction / methods

Substances

  • Polymers
  • Powders
  • Tablets
  • Poloxamer
  • Polyethylene Glycol 6000
  • Polyethylene Glycols
  • Albendazole