Paul Susanta, Majumdar Subhabrota, Chakraborty Mainak, Mukherjee Swarupananda, Sarkar Nilanjan, Prajapati Bhupendra, Ali Nemat, AlAsmari Abdullah F, Nishat Shamama
Department of Pharmaceutical Technology, NSHM Knowledge Campus, Kolkata- Group of Institutions, 124, B.L Saha Road, Kolkata, West Bengal, 700053, India.
Calcutta Institute of Pharmaceutical Technology & Allied Health Sciences, Uluberia, Howrah, West Bengal, 711316, India.
BMC Pharmacol Toxicol. 2025 May 13;26(1):102. doi: 10.1186/s40360-025-00934-y.
Ocular drug delivery is challenging due to the eye's unique anatomy and physiology, which limit drug absorption and distribution. Traditional methods like eye drops have poor bioavailability and often require frequent dosing. In-situ gel systems, liquid formulations that transform into a gel upon contact with physiological conditions (pH, temperature, or ions in tear fluid), offer several advantages for ocular drug delivery. Ganciclovir was incorporated into a thermoresponsive in situ gel base. Nine formulations were prepared using the cold technique and a 3² full factorial design. The physical properties of ganciclovir gel, including clarity, pH, viscosity, gelation temperature, and gelation time, were scrutinized. In vitro drug release was assessed using a dialysis membrane method, and ocular toxicity was evaluated in a rabbit model. Poloxamer 407 and HPMC E-50 LV were used to prepare the gel, with the 3² factorial design analyzing the effects of varying concentrations on the gel's viscosity, gelation temperature, and gelation time. The optimized in-situ gel formulation (Batch B5) contained 15% w/v poloxamer 407 and 1% w/v HPMC E-50 LV, achieving a viscosity of 64.81 cPs, with a gelation temperature of 39.0 °C and a gelation time of 183 s. This formulation demonstrated better permeability and sustained ganciclovir release than a commercial formulation. Ocular toxicity studies confirmed that the formulation was non-irritating and well-tolerated. Overall, the gel showed suitable physical properties, sustained drug release over 12 h, and significant potential for enhancing drug bioavailability and treatment efficacy for ocular infections. These findings confirm that the optimized ganciclovir in situ gel preparation improves eye permeation and prolongs ocular retention time, thus enhancing its therapeutic efficacy. Its sustained release and prolonged retention time make it a promising alternative to conventional eye drops, offering better patient compliance and efficacy.
由于眼睛独特的解剖结构和生理功能限制了药物的吸收和分布，眼部给药具有挑战性。像眼药水这样的传统方法生物利用度差，且通常需要频繁给药。原位凝胶系统是一种在与生理条件（pH值、温度或泪液中的离子）接触时转变为凝胶的液体制剂，为眼部给药提供了几个优点。更昔洛韦被掺入一种热响应性原位凝胶基质中。采用冷技术和3²全因子设计制备了九种制剂。对更昔洛韦凝胶的物理性质，包括澄清度、pH值、粘度、胶凝温度和胶凝时间进行了仔细研究。使用透析膜法评估体外药物释放，并在兔模型中评估眼部毒性。泊洛沙姆407和羟丙甲纤维素E-50 LV用于制备凝胶，3²因子设计分析了不同浓度对凝胶粘度、胶凝温度和胶凝时间的影响。优化后的原位凝胶制剂（批次B5）含有15% w/v泊洛沙姆407和1% w/v羟丙甲纤维素E-50 LV，粘度为64.81厘泊，胶凝温度为39.0℃，胶凝时间为183秒。该制剂比市售制剂表现出更好的渗透性和更昔洛韦的持续释放。眼部毒性研究证实该制剂无刺激性且耐受性良好。总体而言，该凝胶显示出合适的物理性质，在12小时内持续释放药物，并且在提高眼部感染药物的生物利用度和治疗效果方面具有巨大潜力。这些发现证实，优化后的更昔洛韦原位凝胶制剂改善了眼部渗透并延长了眼部滞留时间，从而提高了其治疗效果。其持续释放和延长的滞留时间使其成为传统眼药水的有前途的替代品，具有更好的患者依从性和疗效。
