Formulation of Thermo-Sensitive In Situ Gels Loaded with Dual Spectrum Antibiotics of Azithromycin and Ofloxacin

Polymers (Basel). 2024 Oct 22;16(21):2954. doi: 10.3390/polym16212954.

Abstract

In situ gels have been developed as an innovative strategy to prolong corneal residence time and enhance drug absorption compared to traditional eye drops. Our study aimed to formulate an ophthalmic in situ gel with a combination of two thermosensitive poloxamers, P407 and P188, in an optimal ratio not only to increase the time of action but also to increase the solubility of selected antibiotics for the treatment of ophthalmic infections. Two BSC II class substances, Azithromycin and Ofloxacin, with different mechanisms of action, have been incorporated into the in situ gel system after determining their solubility. The antibiotics-loaded in situ gel formulation was evaluated for its clarity, pH, rheological properties, and gel characteristics of gelling time, temperature, and capacity. The formulation demonstrated satisfactory clarity, appropriate pH, effective gelation properties in simulated tear fluid, and suitable rheological characteristics. In addition, APIs release insight has been studied through a dissolution test, and the effectivity against sensitive and resistant bacterial strains has been proved through the antimicrobial study. Therefore, our in situ gel system based on thermosensitive poloxamers, with two hydrophobic antibiotics, AZM and OFX, can be considered a valuable approach for ophthalmic drug delivery with an enhancement of the antibiotics bioavailability through increasing the contact time with the ocular surface and enhancing patient compliance.

Keywords: Azithromycin; Ofloxacin; antibiotics; drug delivery systems; in situ gel; ocular drug delivery; poloxamers; thermosensitive gels.

Grants and funding

This research was funded by TKP2021-EGA-18 and has been implemented with the support provided by the Ministry of Culture and Innovation of Hungary from the National Research, Development and Innovation Fund, financed under the TKP2021-EGA funding scheme and by 2022-1.2.2-TÉT-IPARI-UZ-2022-00006 Common research and development of different prototypes containing natural herb extract for industrial utilization. The project was also supported by the Stipendium Hungaricum Scholarship.