Increased dissolution of disulfiram by dry milling with silica nanoparticles

Abstract

The purpose of this study was to find a suitable method to increase the dissolution of disulfiram (DSF) which is easily decomposed. The dissolution of DSF within 1 h was significantly increased from 37% to >90% by co-milling with Aerosil® 200 pharm (Aerosil) and the increased dissolution remained stable during long-term storage while there was no significant degradation of DSF. By monitoring the changes in particle size of the grinding mixture, a mosaic DSF-in-Aerosil structure was demonstrated. The core size of the mosaic DSF/Aerosil system was 3.625 µm. The particle size of DSF was reduced from 20.75 µm to ∼200 nm and the size of the mosaic DSF/Aerosil system (3.625∼7.956 µm) increased on increasing the drug-loading content. Differential scanning calorimetry and X-ray powder diffraction analysis confirmed the largely amorphous state of DSF in the mosaic drug/carrier system. Fourier transform infrared spectroscopy confirmed the presence of hydrogen bonding between DSF and Aerosil. Scanning electron microscopy and transmission electron microscopy verified the DSF-in-Aerosil relationship in the particle size determination at different size levels. The possible mechanisms of dry milling included the hypothesis that during impact and collision, DSF particles melted into the surface of Aerosil turning them into an amorphous state or they became inlayed into the interspaces of the Aerosil structure with a much smaller size.

• Aerosil 200 pharm
• amorphous
• disulfiram
• dry milling
• hydrogen bond
• increased dissolution
• mosaic
• stable

Declaration of interest

The authors report no declarations of interest. This work is supported by the National Science & Technology Major Project “Key New Drug Creation and Manufacturing Program” (2013ZX09301305), National High-tech R&D Program of China 863 Program (2012AA020305), Program of International S&T Cooperation and the Doctoral Start-up Fund Program of Liaoning Province, China (20111141), National Natural Science Foundation of China (No. 81102399).