The purpose of this investigation was the evaluation of Bioadhesive Ophthalmic Drug Inserts (BODI) for prolonged release of gentamicin sulfate (GS) in tears. The BODIs (length 5.0 mm, diameter 2.0 mm, weight 20.5 mg, average GS content 5.0 mg) were prepared by extrusion of a mixture based on hydroxypropylcellulose (HPC), ethylcellulose (EC) and carbomer. Two methods were tested to prolong the release of GS in tears: (1) preliminary treatment of GS and (2) use of a less hydrophilic polymer than HPC, hydroxypropylmethylcellulose (HPMC), as a vehicle constituent. The preliminary treatment consisted of the formation of a GS/cellulose acetate phthalate (CAP) solid dispersion (ratio GS/CAP: 10/6) made in acetonic medium, and in the coating of GS/EC granules (GS/EC ratio: 10/0.5) with an aqueous dispersion of CAP, to form a GS/EC/CAP coprecipitate (GS/EC/CAP ratio: 10/0.5/6). Inserts containing GS/CAP solid dispersion, GS/EC/CAP coprecipitate and HPMC resulted in improved time of efficacy (t_eff) (43.8, 23.3, and 33.1 h, respectively), when compared to inserts containing GS without preliminary treatment (t_eff=11.9 h). A high irritation level was observed for inserts containing the GS/EC/CAP and HPMC. A relation between t_eff and irritation score was established, emphasizing the importance of irritability as a factor during the evaluation of the potential of these systems.