Investigation of Drug–Excipient Interactions in Biclotymol Amorphous Solid Dispersions
Résumé
The effect of low molecular weight excipients on drug–excipient interactions, molecular mobility, and propensity to recrystallization of an amorphous active pharmaceutical ingredient is investigated. Two structurally related excipients (α-pentaacetylglucose and β-pentaacetylglucose), five different drug:excipient ratios (1:5, 1:2, 1:1, 2:1, and 5:1, w/w), and three different solid state characterization tools (differential scanning calorimetry, X-ray powder diffraction, and dielectric relaxation spectroscopy) were selected for the present research. Our investigation has shown that the excipient concentration and its molecular structure reveal quasi-identical molecular dynamic behavior of solid dispersions above and below the glass transition temperature. Across to complementary quantum mechanical simulations, we point out a clear indication of a strong interaction between biclotymol and the acetylated saccharides. Moreover, the thermodynamic study on these amorphous solid dispersions highlighted a stabilizing effect of α-pentaacetylglucose regardless of its quantity while an excessive concentration of β-pentaacetylglucose revealed a poor crystallization inhibition. Finally, through long-term stability studies, we also showed the limiting excipient concentration needed to stabilize our amorphous API. Herewith, the developed procedure in this paper appears to be a promising tool for solid-state characterization of complex pharmaceutical formulations.