Development and characterization of olopatadine and verbascoside-loaded thermoresponsive in situ gels for ocular drug delivery: a factorial design approach for allergic conjunctivitis.

内容摘要

Allergic conjunctivitis is one of the most prevalent conditions affecting the eyes, and various medications are used in its treatment. In this study, olopatadine and verbascoside were used in combination. A factorial design was employed to evaluate the effects of Poloxamer 407 and sodium alginate. The impact of polymer concentration on parameters such as viscosity, gelation time, mucoadhesion, pH, and gelation temperature - considered indicators of ideal formulations - was assessed. The optimal formulation, determined through the factorial design, included 0.5% sodium alginate and 20% poloxamer 407. The obtained values were viscosity at 25 °C = 7451.8 cP, viscosity at 35 °C = 11367.3 cP, pH = 7.12, gelation temperature = 30 °C, gelation time = 52 s, and mucoadhesion = 0.301 N. Cytotoxicity tests on ARPE-19 and L929 cells, along with irritation studies, indicated acceptable safety profiles. In vitro release tests demonstrated an initial burst release of verbascoside and olopatadine during the first 2 h, followed by a controlled release over the subsequent 8 h. Mathematical analysis of the release kinetics revealed a good fit with the Weibull model. No adverse effects were observed in rats during Draize's in vivo test. Consequently, the drug-loaded in situ gel formulation may be a promising option for treating allergic conjunctivitis.