The present study involves the development of Dipivefrin hydrochloride (DV) containing Poloxamers (P407 and P188)-Carbopol-934 (CP) based thermoresponsive-gels for the management of elevated intraocular pressure (IOP). Optimal formulation was evaluated for gelation temperature (T_gel), physicochemical and viscoelastic properties, in-vitro gel dissolution and drug release studies. The in-vivo safety, precorneal retention, ocular pharmacokinetics and efficacy in reducing IOP were also evaluated. T_gel of DV-containing thermoresponsive-gels were between 35.1 and 38.9 °C and it was Poloxamers and CP concentrations dependent. The optimal formulation (F8), composed of 20% P407, 5% P188 and 0.15% CP (w/v), had a T_gel of 35 °C. Its viscosity indicated good flow at room temperature and ability to convert to gel at ocular temperature and the rheology studies revealed favorable characteristics for its ocular use. In precorneal retention experiment, F8 indicated significantly higher area under concentrations curves as compared to DV-aqueous suspension (DV-AqS). In-vivo ocular pharmacokinetics indicated a significant improvement in ophthalmic bioavailability of epinephrine (active form of DV). F8 was non-irritant to the eyes and showed a successful, continuous and superior ability to reduce IOP compared to DV-AqS in rabbits. In conclusion, our developed system could be an appropriate substitute to the conventional DV eye preparations in the management of elevated IOP.

本研究涉及开发含有泊洛沙姆（P407和P188）-Carbopol-934（CP）的热响应性凝胶的盐酸地比夫林（DV），用于治疗眼内压升高（IOP）。评估了最佳制剂的胶凝温度（T _gel），理化和粘弹性，体外凝胶溶解和药物释放研究。该被检体内的安全性，角膜前保留，眼药代动力学和药效降低眼压也进行了评价。含DV的热敏_凝胶的T_凝胶在35.1至38.9°C之间，且与泊洛沙姆和CP浓度有关。由20％P407、5％P188和0.15％CP（w / v）组成的最佳配方（F8）具有T_凝胶35°C。它的粘度表明在室温下具有良好的流动性，并且在眼温下具有转化为凝胶的能力，流变学研究表明其在眼内使用具有良好的特性。在角膜前保留实验中，与DV悬浮液（DV-AqS）相比，F8浓度曲线下的面积明显更高。体内眼药代动力学表明肾上腺素（DV的活性形式）的眼用生物利用度有显着改善。与兔的DV-AqS相比，F8对眼睛无刺激，并显示出成功，连续且出色的降低IOP的能力。总而言之，我们开发的系统可以替代传统的DV眼部制剂，以治疗高眼压。