An ocular insert with zero-order extended delivery: Release kinetics and mathematical models

Ocular inserts (InEye (R)), were prepared based on two distinct formulations of PCL-PEG-PCL block copolymers - one with 33 % and the other with 24 % of PEG 600. Ring-open-polymerisation was used to link epsilon-caprolactone monomers to PEG hydroxyl end-groups. Molecular weight, PCL/PEG ratio, mass loss and swelling of different polymeric samples where determined.Based on the previously prepared block copolymers, ophthalmic inserts were assembled. These were prepared with an ellipsoidal shape by dripping melted polymer over a micro-tablet of moxifloxacin, used as drug model for this study, which therefore became entrapped in a central core coated with a polymer layer that functioned as a control-release barrier.The release kinetics of the model drug revealed a strong dependence on the PEG percentage on the polymer. Inserts' size and the amount of drug immobilized also had an important effect on the drug release profile. All release profiles followed a zero-order pattern, with 95 % of the drug being release at a constant rate.With drug releases varying from 20 to 200 days, and no initial burst, InEye (R) performance is unique among drug delivery systems and seems to be a very promising new formulation technology for preparing tailor-made ophthalmic inserts for prolonged and constant release of drug, which is needed for chronic diseases such as glaucoma, where compliance to treatment is essential for preventing optic-nerve lesions.

Automated summary

Ocular inserts based on PCL-PEG-PCL block copolymers were prepared and showed promising potential for prolonged and constant drug release. The release kinetics were influenced by the percentage of PEG in the polymer and the size of the inserts. This new formulation technology has great significance for chronic diseases like glaucoma.