Extended Sustained Release of Propranolol Hydrochloride from Siloxane-Poly(propylene Oxide) Hybrid Material: A Multistep Mechanism

Si NMR. The coupling of the hydrophobic character of the polymer with the hydrophilic nature of the siloxane nanoparticles and the urea groups located at the polymer chain extremities enabled prolonged drug release, extending up to two months. A shift from near-continuous delivery to a stair-type profile was observed when the drug loading was increased from 5 to 30 wt %. This was due to a significant increase in the fraction of drug crystallites dispersed between the hydrophobic polymer chains, as revealed by XRD, DSC, and TGA measurements, with XRD and DSC analyses also showing that penetration of water into the hybrid matrix was very slow. This caused the formation of a wet surface and a dry core within the material, leading to release according to several non-Fickian mechanisms, involving only the drug crystallites in the first steps of the process. Small-angle X-ray scattering (SAXS) analysis revealed nanoscale structural variations associated with oscillatory polymer chain expansion and contraction during the release. These pump-like changes, together with the morphological evolution of the surface and core of the hybrid material, confirmed a slow process of dissolution-diffusion of the embedded drug crystals. This generated a self-refilling reservoir effect, which maintained a steady drug flux at the interface, with the mechanisms of anomalous transport and Fickian diffusion allowing the release of the drug molecules located in the more hydrophilic nanodomains of the hybrid network after longer times. This extended the therapeutic availability of the drug, without burst release or external refilling.