Abstract
Disulfiram (DSF) is an approved treatment for chronic alcoholism by inhibiting acetaldehyde dehydrogenase to increase ethanol sensitivity. It is also being explored for treatment of autoimmune, inflammatory, and viral diseases. As a Biopharmaceutics Classification System Class II drug, DSF has low solubility (4.09 mg/L at 25 °C) but high permeability, which limits its dissolution and bioavailability. This study aimed to improve DSF solubility and dissolution using particle size reduction and spray-dried solid dispersions.
Solid dispersions of DSF were prepared using a commercial graft amphiphilic co-polymer carrier, Soluplus (SOL), at different weight ratios of 1:5, 1:1, and 5:1 of DSF:SOL. The powder samples were characterised using scanning electron microscopy (SEM) to assess particle morphology, Fourier-transform infrared spectroscopy (FTIR) for molecular interactions and dynamic scanning calorimetry (DSC) to analyse solid-state properties. Drug content and water solubility tests were conducted at room temperature. The dissolution test was performed using the US Pharmacopeia Apparatus 2.
According to SEM analysis, the 1:5 DSF-SOL powder particles were smooth and non-spherical, with an average size of 10.087 ± 6.931 μm. In FTIR results, the dipole-dipole interactions between DSF and SOL in DSF-SOL powder led to decreased transmittance spectra at the chemical bond of both DSF and SOL molecules. DSC data showed crystalline events for spray-dried DSF, while DSF-SOL displayed amorphous events, confirming the solid dispersion of DSF-SOL particles. The 1:5 DSF-SOL spray-dried powders showed up to an 8.7-fold increase in the DSF solubility and showed rapid dissolution, releasing over 80% DSF within 5 minutes.
This study successfully developed DSF-SOL solid dispersions with enhanced solubility and dissolution of DSF. The powder formulations can be developed into solid dosage forms to improve DSF bioavailability. Future studies, such as permeation through dialysis membranes, can determine if the solid dispersions have unchanged permeability for improved bioavailability from the solid dosage form.