Release Rates of Prednisolone-21-Hydrogen- Succinate from 3D-Printed Silicone as Material for Patient-Individualized Drug Releasing Implants

Abstract For treating idiopathic sudden sensorineural hearing loss, prednisolone is commonly used. However, systemic or middle ear injections often lead to insufficient drug delivery to the inner ear, causing ineffective treatment and systemic side effects. An implant inserted into the middle ear and delivering the drug directly to the inner ear offers a promising solution, providing controlled, long-term drug release with potentially better efficacy and fewer side effects. Individualized implants made of prednisolone-containing silicone can optimize inner ear treatment by fitting the patient's middle ear anatomy. To gauge the properties of prednisolone-21- hydrogen succinate containing silicone, samples with different geometries and drug concentrations have been 3D-printed. The shore hardness of samples with three different drug concentrations was assessed. Three different shapes with four different drug concentrations were incubated in artificial perilymph for up to 56 days to evaluate the release rates. The resulting eluates were analyzed via Ultra high precision liquid chromatography coupled with a time-of-flight micro-mass spectrometer. Samples were softer when a higher drug concentration was used. A high burst release of prednisolone after one hour was measured. Afterward, the release rates decreased and reached a relatively constant rate after ten days and stayed there for at least another 46 days. The release rates were multiple times higher when the samples had a higher surface-to-volume ratio. The softer the sample, the higher the release rate, unproportional to the concentration increase.