Hybrid Ear Cubes for local controlled dexamethasone delivery to the inner ear

• Published in: European journal of pharmaceutical sciences Vol. 126; pp. 23 - 32
• Main Authors: Gehrke, M., Verin, J., Gnansia, D., Tourrel, G., Risoud, M., Vincent, C., Siepmann, F., Siepmann, J.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.01.2019
• Series: European journal of pharmaceutical sciences . official journal of the European Federation for Pharmaceutical Sciences
• Subjects: Cochlea; Dexamethasone; Dexamethasone - administration & dosage; Drug Compounding; Drug Implants; Drug Liberation; Humans; Implant; Kinetics; Life Sciences; Local controlled drug delivery; Perilymph; Silicone; Silicones - chemistry; Cochlea; Local controlled drug delivery; Dexamethasone; Implant; Silicone
• ISSN: 0928-0987; 1879-0720; 1879-0720
• DOI: 10.1016/j.ejps.2018.04.045

A new type of miniaturized implants for local controlled drug delivery to the inner ear is proposed: Hybrid Ear Cubes. They are composed of two main parts: (i) a cylinder, which is placed into a tiny hole (<0.4 mm) drilled into (or close to) the oval (or round) window, and (ii) a cuboid, which is placed into the middle ear. The drug is released at a pre-programmed rate into the perilymph: (i) via the cylindrical part of the implant, which is in direct contact with this liquid, and (ii) via diffusion from the cuboid through the oval/round window. Importantly, the cylindrical part assures a reliable fixation of the drug delivery system at the site of administration. Furthermore, the cuboid provides a relatively “large” drug reservoir, without expulsing perilymph from the cochlea. The required surgery is minimized compared to the placement of an intracochlear implant. In contrast to previously proposed Ear Cubes, which are mono-block systems, Hybrid Ear Cubes consist of two halves, which can: (i) be loaded with different drugs, (ii) be loaded with the same drug at different concentrations, and/or (iii) be based on two different matrix formers. This offers a substantially increased formulation flexibility. Different types of silicone-based Hybrid Ear Cubes were prepared, loaded with 10% dexamethasone in one half and 0–60% dexamethasone in the other half. Importantly, tiny drug crystals were homogeneously distributed throughout the respective implant halves. The observed drug release rates were very low (e.g., <0.5% after 2 months), which can be attributed to the type of drug and silicone as well as to the very small surface area exposed to the release medium. Importantly, no noteworthy implant swelling was observed. [Display omitted]