Dry amorphisation of mangiferin, a poorly water-soluble compound, using mesoporous silica

• Published in: European journal of pharmaceutics and biopharmaceutics Vol. 141; pp. 172 - 179
• Main Authors: Baán, Adrienn, Adriaensens, Peter, Lammens, Joris, Delgado Hernandez, René, Vanden Berghe, Wim, Pieters, Luc, Vervaet, Chris, Kiekens, Filip
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.08.2019
• Subjects: Co-milling; Drug formulation; Dry amorphisation; Mesoporous silica; Solid dispersions; Solubility improvement; Solubility improvement; Solid dispersions; Drug formulation; Dry amorphisation; Mesoporous silica; Co-milling
• ISSN: 0939-6411; 1873-3441
• DOI: 10.1016/j.ejpb.2019.05.026

[Display omitted] Mangiferin, a poorly water soluble compound, was processed via a dry amorphisation technique (ball milling) in combination with mesoporous silica to enhance the solubility of mangiferin. The amorphous samples were prepared by mixing 1:1 (w/w) Syloid® XDP 3050 silica-mangiferin mixtures using a planetary mono mill at different milling speeds and milling times according to a 32 full factorial experimental design. The prepared samples were characterized for dissolution profile, particle size distribution using laser diffraction particle size analyzer, thermal characteristics using DSC, crystalline characteristics using XRD 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 improve stability of the samples, mixtures of 1:1:2 mangiferin-polymer (Soluplus or HPMC)-silica samples were also prepared and analyzed. Amorphisation of mangiferin is possible using dry amorphisation by ball milling with mesoporous silica in a short amount of time. The amorphisation rate of the samples improved with the energy input of the milling process. The samples prepared with high energy input resulted in amorphous samples and showed a better stability at the stress conditions for up to 3 months. Solubility of these samples increased from 0.32 to 0.50 mg/ml and the particle size decreased from 35.5 µm to around 7 µm. The spectral analysis suggest presence of interactions between the silica material and the compound. The amorphous stability was improved with addition of polymer, even though the solubility of the samples was lower.