Design and evaluation of ocular hydrogel containing combination of ofloxacin and dexamethasone for the treatment of conjunctivitis

Abstract Conjunctivitis is an inflammation of the conjunctiva, which covers the white part of the eyeball. It can be caused by allergies, bacterial or viral infection. In situ hydrogels are three-dimensional hydrophilic cross-linked network of polymers. In situ hydrogel provided better therapeutic index when compared to conventional treatment. The present work describes the formulation and evaluation of ofloxacin and dexamethasone based on the concept of pH triggered in situ gelation. Carbopol 934p was used as the gelling agent in combination with HPMC, as a viscosity-enhancing agent, benzalkonium chloride as preservative, sodium chloride as tonicity adjusting agent. The prepared formulations were liquid at the low pH and underwent rapid transition into viscous gel at the pH of the tear fluid. Formulations were evaluated for various rheological, in vitro and in vivo release characteristics. Infrared spectroscopy studies showed that there were no interactions between the drug and polymers. Viscosity of the prepared hydrogels lies in the optimum range and drug was released up to 85 % as the end of 13 h. The prepared in situ hydrogel was sterile, non-irritant to the eye. The present study indicated that it is possible to develop safe and physiologically effective in situ hydrogel which is patient compliant.

摘要 结膜炎是覆盖眼球巩膜（眼白部分）的结膜发生的炎症反应，可由过敏反应、细菌或病毒感染诱发。原位水凝胶（in situ hydrogel）是一类具备三维亲水性交联聚合物网络的高分子材料。相较于传统治疗手段，原位水凝胶可展现更优异的治疗指数。本研究基于pH触发原位成胶的理念，阐述了氧氟沙星与地塞米松复方制剂的制备与评价方法。本研究以卡波姆934p（Carbopol 934p）作为胶凝剂，辅以羟丙基甲基纤维素（HPMC）作为黏度增强剂，苯扎氯铵作为防腐剂，氯化钠作为渗透压调节剂。所制备的制剂在低pH环境下呈液态，在接触泪液pH时可快速转变为黏性凝胶。对所得制剂开展了多项流变学、体外及体内释放特性评价。红外光谱法研究显示，药物与聚合物之间未出现相互作用。所制备水凝胶的黏度处于最优区间，13小时终末期药物累积释放率可达85%。所得原位水凝胶无菌、对眼部无刺激性。本研究表明，开发安全合规、生理适配性良好且患者依从性佳的原位水凝胶制剂具备可行性。