Innovative triamcinolone acetonide microsuspension for Non-Invasive ocular management of inflammation.

Abstract

Enhancing the bioavailability of insoluble active agents in the eye through topical administration is a key focus in formulation science. This study aims to develop a microsuspension-based drug delivery system to effectively deliver anti-inflammatory drugs to deeper ocular tissues, offering a non-invasive alternative to intraocular injections.

Methods: To improve the bioavailability of the hydrophobic drug triamcinolone acetonide (TA), we reduced its particle size using the wet ball milling method with zirconium oxide beads. To enhance mucus penetration, we coated the TA microsuspension with the non-ionic surfactant Poloxamer 407. The microsuspension was characterized for morphology, particle size, zeta potential, and dissolution properties in various ocular media. We also modeled TA distribution in different ocular compartments using GastroPlus™ software and evaluated the impact of formulation parameters such as particle size and viscosity.

Results: Reducing the particle size to 250 nm significantly increased the dissolution rate of the microsuspension. The model indicated that viscosity and particle size are critical for enhancing the ocular concentration of eye drops in various tissues. Optimizing these parameters could lead to a nearly 40-fold reduction in the required TA eye drop dosage (from 4.0% w/v to 0.1% w/v).

Conclusion: Our findings suggest that a TA formulation with a particle size of 1.0 μm or less and a viscosity of about 72.0 cp. can be as effective as a larger particle size formulation while delivering significantly higher TA concentrations. The enhanced uniformity, re-dispersibility, and improved distribution to ocular tissues position this microsuspension as a novel approach to overcoming ocular drug delivery challenges and reducing the need for intraocular injections.