Evaluation of pentablock co-polymer (PTSsol) for sustained topical ocular drug delivery

The purpose of this study is to evaluate ocular retention, tolerability, and sustained pharmacodynamics of a clear topical formulation of brinzolamide (BRZ) in PTSsol pentablock co-polymer. To test for ocular retention, PTSsol or saline containing near infrared dye-labeled (NIR) IgG was applied to the corneal surface of mice and monitored by in vivo imaging. To evaluate pharmacodynamics, dogs were dosed for 3 consecutive days with PTSsol once daily (qd) at doses of 1% and 2.5% and compared to PTSsol qd, or commercial BRZ 1% (Azopt®) three times daily (tid). Intraocular pressure (IOP) and ocular exams were performed each treatment day and two additional days post-treatment. The NIR-IgG saline remained on the ocular surface for <3 h, while NIR-IgG in PTSsol remained for >21 h. All formulations were well tolerated in dogs and by day 3 of dosing, IOP was significantly lower in 2.5% BRZ PTSsol qd dosed eyes compared to vehicle or baseline (p < 0.014). On day 5, 48 h after dosing, IOP remained significantly lower in eyes treated with 2.5% BRZ PTSsol qd compared to those dosed with Azopt (p = 0.036). This suggests that drugs in PTSsol may allow for once a day or less frequent dosing.