EVALUATION OF SOLUBLE BIOADHESIVE OPHTHALMIC DRUG INSERTS (BODI(R)) FOR PROLONGED RELEASE OF GENTAMICIN - LACRIMAL PHARMACOKINETICS AND OCULAR TOLERANCE

The purpose of this investigation was the evaluation of Bioadhesive Op hthalmic Drug Inserts (BODI) for prolonged release of gentamicin sulfa te (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 mixt ure based on hydroxypropylcellulose (HPC), ethylcellulose (EC) and car bomer. Two methods were tested to prolong the release of GS in tears: (1) preliminary treatment of GS and (2) use of a less hydrophilic poly mer than HPC, hydroxypropylmethylcellulose (HPMC), as a vehicle consti tuent. The preliminary treatment consisted of the formation of a GS/ce llulose acetate phthalate (CAP) solid dispersion (ratio GS/CAP: 10/6) made in acetonic medium, and in the coating of GS/EC granules (GS/EC r atio: 10/0.5) with an aqueous dispersion of CAP, to form a GS/EC/CAP c oprecipitate (GS/EC/CAP ratio: 10/0.5/6). Inserts containing GS/CAP so lid 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(ef f) = 11.9 h). A high irritation level was observed for inserts contain ing the GS/EC/CAP and HPMC. A relation between t(eff) and irritation s core was established, emphasizing the importance of irritability as a factor during the evaluation of the potential of these systems.