Silicone rubber hydrogel composite ophthalmic inserts: preparation and preliminary in vitro in vivo evaluation

The present report describes the development and in vitro/in vivo testing of rod-shaped mucoadhesive ophthalmic inserts fitting the upper or lower conjunctival fornix. Cylindrical devices (diameter 0.9 mm, length 6-12 mm, weight 3-8 mg) all containing 0.8 mg oxytetracycline HCl (OXT) were prepared from appropriate mixtures of silicone elastomer, OXT and sodium chloride as release modifier. A stable polyacrylic acid (PAA) or polymethacrylic acid (PMA) interpenetrating polymer network (IPN; 30 or 46% w/w) was grafted onto the inserts' surface by treatment with a mixture of acrylic (or methacrylic) acid and ethylene glycol dimethacrylate in xylene at 100 degrees C. Mucodhesion studies in vitro showed that the mucoadhesive properties increased significantly with increasing thickness of the IPN layer. The inserts were tested for drug release in vitro, and for drug release and retention in rabbit eyes. The presence of IPN, as well as of NaCl, in general increased the drug release rate. The PMA-grafted devices released OXT at lower rates when compared with the PAA-grafted ones. A nearly zero-order release rate for about I week was observed in vitro for some types of inserts. When tested in rabbits, some IPN-grafted inserts maintained in the lacrimal fluid a OXT concentration of 20-30 mu g/ml for several days: the in vitro minimum inhibitory concentration values (MIC 90%) of OXT against micro-organisms responsible of common ocular infections range from 0.8 to 2.0 mu g/ml, while MIC 90% values in the range 14-50 mu g/ml have been indicated for Pseudomonas aeruginosa. The ocular retention of IPN-grafted samples was significantly higher with respect to ungrafted ones. The presently described mucoadhesive silicone inserts might prove efficient therapeutic systems for chemotherapy of ocular bacterial infections, such as trachoma. (C) 1998 Elsevier Science B.V. All rights reserved.