Solid dispersions of drugs in hyaluronan matrix: The role of the biopolymer in modulating drug activity in vivo
Résumé
It was demonstrated in this study that the treatment of physical mixtures of hyaluronic acid (HA) and oncology drugs raloxifene, letrozole, and irinotecan in solid state under shear stress and deformation induces amorphization of the drug component. Such loss of crystallinity favors dispersion of drugs in HA matrix at a molecular level. Upon dissolution, the composites of poorly soluble raloxifene and letrozole form various solvated species that may include drug-HA composites, large agglomerates, and possibly free drug nanoparticles. Amorphous character of drug component and their stabilization in solution by HA leads to improved oral bioavailability of raloxifene and letrozole, but not irinotecan, as demonstrated in pharmacokinetics studies in rats.