Comparison of systemic absorption between ofloxacin ophthalmic in situ gels and ofloxacin conventional ophthalmic solutions administration to rabbit eyes by HPLC–MS/MS

In recent years, many pharmaceutical scientists have focused on developing the in situ gel-forming systems to overcome the poor bioavailability and therapeutic response exhibited by conventional ophthalmic solutions due to rapid pre-corneal elimination of the drug. The present work was to compare the systemic absorptions of ophthalmic ofloxacin in situ gel with the conventional ofloxacin eye drop after topical instillation to rabbit eyes by HPLC–MS/MS method and also determine the relative contribution of the nasal and the conjunctival mucosae to systemic ofloxacin absorption following topical instillation. The systemic AUC, Cmax, Tmax and Ke for ophthalmic in situ gel and ophthalmic solution after ocular instillation were 202.63 ± 118.85 and 202.25 ± 57.74 ng mL-1 h, 54.22 ± 28.31 and 48.4 ± 25.97 ng mL-1, 1.08 ± 0.20 and 1.25 ± 0.88 h, 0.0576 ± 0.0207 and 0.0388 ± 0.0248, respectively. And the values for the ratios of the AUC of anterior chamber of rabbit eye to blood plasma, AUCac/AUCpl, for ofloxacin conventional eye drop and in situ gel were 0.25 and 0.52, respectively. Statistic results showed that there was no significant difference in systemic absorption between the test groups and the reference groups (P > 0.05) as both formulations have an AUCsa/AUCpl of 0.35. Therefore, the ophthalmic in situ gel may not decrease the drugs systemic absorption when administered in an equivalent dose as ophthalmic solutions into the rabbit eyes.

Graphical abstractThe plasma ofloxacin concentration–time profiles following a 100-µL topical dose in conscious rabbits (n = 6). (■) test group; (□) reference group.Figure optionsDownload full-size imageDownload high-quality image (79 K)Download as PowerPoint slide