Department of Pharmaceutical Technologies, Faculty of Pharmacy, Medical University - Varna "Prof. Dr. Paraskev Stoyanov", 84 Tsar Osvoboditel Str., 9000 Varna, Bulgaria.
Department of Pharmaceutical Sciences and Social Pharmacy, Faculty of Pharmacy, Medical University - Pleven, Bulgaria.
Int J Pharm. 2020 Dec 15;591:120010. doi: 10.1016/j.ijpharm.2020.120010. Epub 2020 Oct 22.
The present study was focused on the development of doxycycline niosomal thermosensitive in situ gel for ophthalmic application. For this purpose, in situ gel formulations based on Poloxamer 407 alone and in combination with hydroxypropyl methylcellulose were prepared by cold method and evaluated in terms of sol-gel transition temperature, gelling time and capacity. The addition of hydroxypropyl methylcellulose to the composition led to decrease in the phase transition temperature of the systems. Conversely, the inclusion of doxycycline niosomes to the formulations didn''t have a significant influence on their gelling and rheological properties. Doxycycline niosomal in situ gel based on 15%w/w Poloxamer and 1.5% w/w hydroxypropyl methylcellulose was characterized with gelation temperature of 34 °C, appropriate for ophthalmic application, pseudoplastic flow behavior and very good physical stability. In vitro release studies indicated slower and sustained doxycycline release from the developed in situ gel as compared to niosomes. The conducted microbiological studies revealed its enhanced antibacterial activity with respect to doxycycline solution and doxycycline in situ gel. The obtained results indicate that the elaborated niosomal in situ gel may serve as a promising system for ophthalmic delivery of doxycycline, ensuring sufficient therapeutic concentration and sustained drug release.
本研究专注于开发用于眼部应用的盐酸多西环素囊泡温敏原位凝胶。为此，通过冷法制备了基于泊洛沙姆 407 单独和与羟丙基甲基纤维素组合的原位凝胶制剂，并从溶胶-凝胶转变温度、胶凝时间和胶凝能力方面进行了评价。向组合物中添加羟丙基甲基纤维素会降低体系的相变温度。相反，将盐酸多西环素囊泡加入到制剂中对其胶凝和流变性能没有显著影响。基于 15%w/w 泊洛沙姆和 1.5%w/w 羟丙基甲基纤维素的盐酸多西环素囊泡原位凝胶的胶凝温度为 34°C，适用于眼部应用，具有假塑性流动行为和非常好的物理稳定性。体外释放研究表明，与囊泡相比，开发的原位凝胶中盐酸多西环素的释放更缓慢且更持久。进行的微生物研究表明，与盐酸多西环素溶液和盐酸多西环素原位凝胶相比，其具有增强的抗菌活性。所得结果表明，所阐述的囊泡原位凝胶可用作眼部递送盐酸多西环素的有前途的系统，确保足够的治疗浓度和持续的药物释放。
