Effect of Particle Size and Viscosity of Suspensions on Topical Ocular Bioavailability of Budesonide, a Corticosteroid

Purpose: To determine the effect of particle size and viscosity of suspensions on topical ocular bioavailability of budesonide, a corticosteroid drug. Methods: Budesonide microparticle and nanoparticle (MP and NP) suspensions were prepared with or without homogenization and microfluidization. Using different grades of hydroxyl propyl methyl cellulose, low viscosity NP (NP-LV) and low and high viscosity MP (MP-LV and MP-HV) were prepared. Suspensions were characterized for particle size, viscosity, and osmolality. Budesonide suspensions were administered topically to rabbits and aqueous humor was collected and analyzed for budesonide. Budesonide C max , t max , and the area under the concentration time curve (AUC (0–6h) ) values were determined. The geometric mean ratio of AUC and bioequivalence was evaluated using a bootstrap method. Results: The particle sizes for NP and MP were ∼700 and 2,000 nm. The viscosities for low and HV formulations were ∼5 and 50 cP. The geometric mean budesonide C max values for the suspensions NP-LV, MP-LV, and MP-HV were 0.22, 0.22, and 0.31 μg/g, t max values were 0.67, 0.60 and 0.53 h, and AUC 0–6h values were 0.72, 0.53, and 0.95 μg h/g, respectively. Bootstrap analysis indicated that the 90% confidence intervals of the geometric mean ratio of AUC 0–6h values were 1.00–1.74 (MP-HV vs. NP-LV), 0.57–0.96 (MP-LV vs. NP-LV), and 0.45–0.70 (MP-LV vs. MP-HV). Conclusions: The 3 budesonide suspensions assessed in this study were not bioequivalent. Results suggested that an increase in viscosity improves the bioavailability of budesonide from the microsuspension formulation.