In vitro and in vivo evaluation of ocular inserts of ofloxacin

Ocular inserts of ofloxacin were prepared with objectives of reducing the frequency of administration, obtaining controlled release and greater therapeutic efficacy in the treatment of eye infections such as conjunctivitis, keratitis, corneal ulcers, etc. Polyvinyl alcohol (PVA) ofloxacin films were prepared by mercury substrate method. The ocular inserts were evaluated for drug-excipient interaction, physico-chemical characteristics, microbiological and in vitro and in vivo release studies. There was no interaction between drug and excipients as revealed by UV absorption and IR spectra of the pure drug, medicated and placebo formulations. The weight and thickness of the inserts were in the range of 57.3-126.0 mg and 55.6-99.3 microns, respectively for different formulations; casting of rate-controlling membrane increased the weight and thickness of the inserts. Tensile strength and percent elongation at break varied with the nature of rate-controlling membrane and film thickness. Moisture vapour transmission through films followed zero-order kinetics and decreased with increase in film thickness. The drug content varied from 99.53-99.86%. The method of exposure to UV radiation was used for sterilization of ocular inserts and no microbial growth was observed in any formulation during sterility testing by direct inoculation method. The influence of rate-controlling membrane of different polymers of ethyl cellulose (EC) and polymethacrylates (Eudragit RL 100, Eudragit RS 100) on release kinetics was studied. The drug release for prepared formulations with rate-control ling membrane of EC, Eudragit RS 100 (ERS), Eudragit RL 100 (ERL) was found to be 85.80, 93.85 and 98.71%, respectively and followed zero-order kinetics. Ocular insert F3 with rate-controlling membrane of Eudragit RS 100, when inserted into the eye of rabbit showed controlled release up to 24 hours. There was a good correlation between in vitro and in vivo release data. The developed formulation was effective against selected microorganism during in vitro antimicrobial efficacy studies. PVA-ofloxacin ocular inserts with rate-controlling membrane of Eudragit RS 100 are promising for controlled ocular delivery of ofloxacin.