Melt-Cast Noninvasive Ocular Inserts for Posterior Segment Drug Delivery

The objective of the present study was to evaluate the utility of melt-cast, topical, ocular inserts for delivery of drugs with different physicochemical properties. The model drugs tested include indomethacin (IN), ciprofloxacin hydrochloride, and prednisolone sodium phosphate. Melt-cast method was used to fabricate ophthalmic inserts. Polyethylene oxide N10, a semicrystalline thermoplastic polymer (polyethylene oxide N10; Mol. wt: 100 kDa) was used as the matrix-forming material. Polymeric insert units (4 x 2 x 0.2 mm) with a 10% w/w drug load were tested for in vitro release, transmembrane permeability, and in vivo ocular tissue distribution. Marketed ophthalmic solutions were used as control solutions. Drug content in all the formulations ranged between 93% and 102% of the theoretical value. Transmembrane flux of IN, prednisolone sodium phosphate, and ciprofloxacin hydrochloride was enhanced by similar to 3.5-folds, similar to 3.6-folds, and similar to 2.9-folds, respectively, from the polymeric inserts compared with the control formulations, after 3 h. Moreover, ocular inserts generated significantly higher drug levels in all the ocular tissues, including the retina-choroid, compared with their control formulations. The melt-cast ophthalmic inserts show promise as an effective noninvasive ocular drug delivery platform, which will be highly beneficial in the intervention and treatment of a wide variety of ocular complications. (C) 2017 American Pharmacists Association (R). Published by Elsevier Inc. All rights reserved.