Preservative-Free Triamcinolone Acetonide Suspension Developed for Intravitreal Injection

摘要

Objectives: All commercially available triamcinolone acetonide (TACA) suspensions, used for intravitreal treatment, contain retinal toxic vehicles (e.g., benzyl alcohol, solubilizer). Our aim was to find a convenient and reproducible method to compound a completely preservative-free TACA suspension, adapted to the intraocular physiology, with consistent quality (i.e., proven sterility and stability, constant content and dose uniformity, defined particle size, and 1 year shelf life).nnMethods: We evaluated two published (Membrane-filter, Centrifugation) and a newly developed method (Direct Suspending) to compound TACA suspensions for intravitreal injection. Parameters as TACA content (HPLC), particle size (microscopy and laser spectrometry), sterility, and bacterial endotoxins were assessed. Stability testing (at room temperature and 40°C) was performed: color and homogeneity (visually), particle size (microscopically), TACA content and dose uniformity (HPLC) were analyzed according to International Conference on Harmonisation guidelines.nnResults: Contrary to the known methods, the direct suspending method is convenient, provides a TACA suspension, which fulfills all compendial requirements, and has a 2-year shelf life.nnConclusions: We developed a simple, reproducible method to compound stable, completely preservative-free TACA suspensions with a reasonable shelf-life, which enables to study the effect of intravitreal TACA—not biased by varying doses and toxic compounds or their residues.