Enhancement of the bioavailability of poorly water-soluble compounds via amorphisation is of high interest. In this study a promising therapeutic polyphenol, the mangiferin was processed via ball milling in combination with mesoporous silica or a mixture of a polimer and mesoporous silica. The compound required a novel technology without the use of organic solvents due to its poor solubility not only in water, but also in organic solvents.
The amorphous samples were prepared using a Pulverisette 6 planetary ball mill (Fritsch, Oberstein, Germany). The compound and mesoporous silica (Syloid XDP3050) were mixed in a 1:1 weight ratio (total mass: 8 g) and this mixture was placed in a 250 ml zirconium dioxide vessel with 50 zirconium dioxide balls (diameter: 10 mm). The milling speed was varied between 400 and 600 rpm, and the milling time was 1 to 20 minutes according to an experimental design. The prepared samples were characterized for dissolution profile, particle size distribution, thermal characteristics using DSC and molecular interactions using FTIR and ss-NMR. The samples were tested for stability at stress conditions (40°C/75%RH) for up to 6 months in open and closed containers. To evaluate the stability improvement by addition of polymers, samples of mangiferin, polymer (HPMC or Soluplus) and mesoporous silica were prepared in a ratio of 1:1:2 respectively.
Amorphisation of the poorly soluble compound was possible via dry amorphisation in ball mill in combination with mesoporous silica in already 10 minutes at high rotational speed. The amorphisation rate of the samples was correlated with the energy input during the milling process. The samples prepared with high energy input resulted in fully amorphous samples which showed a good stability at the stress conditions for up to 3 months. Solubility of these samples increased from 0.3 to 0.5 mg/ml and the particle size decreased from 35.5 µm to around 7 µm. The spectral analysis suggested that molecular interactions occurred between the silica material and the compound. Addition of polymer did improve the stability of samples, after 3 months one sample was still amorphous in open condition.
The results showed that – depending of the settings during ball milling - molecular interaction could be induced between mesoporous silica and the compound, resulting in an amorphous system with increased solubility and stability was improved by addition of polymer.