Exploratory ocular surface distribution studies of Azithromycin formulations based on semifluorinated alkanes

Abstract

PurposeAzithromycin is an antimicrobial agent with broad spectrum activity and anti‐inflammatory properties. The aim of this study was to investigate the ocular distribution of azithromycin after a single topical instillation of a new semifluorinated alkane (SFA) based formulation in rabbits.MethodsRabbits were treated with either a single administration of 1.5% or 3% SFA‐azithromycin suspensions. Due to the low surface and interface tension of the SFA, and its excellent spreading properties, droplet size is smaller compared to other ophthalmic formulations which lead to a low instillation volume of ~11 μL. Tears (T), aqueous humor (AH), cornea (C), bulbar conjunctiva (BCJ), and eyelids (EL) from individual eyes were collected up to 144 h post dosing and drug concentrations were measured using a validated LC‐MS/MS method.ResultsFollowing a single topical instillation of SFA‐azithromycin in rabbit eyes, both formulations were macroscopically well tolerated. The highest exposure was found in the general order of EL > T > C > BCJ > AH. The obtained values were compared with data from a similar experiment of a marketed 1.5% azithromycin formulation in medium‐chain triglycerides1, with a single instillation of 25 μL. The comparison showed that azithromycin exposure after administration of 1.5% SFA‐azithromycin formulation was similar to the marketed formulation despite the lower absolute dose.Amar et al, Current Eye Research, 33: 149‐158, 2008ConclusionsThe preservative‐free, multi‐dose SFA‐azithromycin formulation was well tolerated. Both concentrations resulted in adequate and long‐lasting azithromycin levels in T and EL, C and BCJ. Based on these results this azithromycin formulation may lead to a new therapeutic well‐tolerated option in treating ocular surface bacterial infections.