Drug loading strategies and processing of polymer blends for intraocular controlled drug release application

In 2010 there were 60.5 million people with glaucoma worldwide and this number is expected to increase to 79.6 million by 2020. In most glaucoma patients medical therapy consists of topical eyedrops. However, administration and compliance are often problematic. Surgical and laser treatment for glaucoma is traumatic for the patients, involving high costs and might require repetition of the procedure. Therefore the aim of the present work was the development of drug-eluting biodegradable implants designed to provide a localized and long-term (6 months to 2 years) sustained release of the drug that can be used in the treatment of glaucoma. The implant should degrade within the site of implantation, eliminating the need for further surgery. The implant should be introduced in the ophthalmologist o ce, under local anaesthesia, with high implications in patient recovery and costs. By delivering controlled amounts of drug the implant would be pharmacologically e cient and increase patient compliance. Several polymer processing and drug loading techniques were used in order to prepare controlled drug delivery systems (CDDS) for intraocular application. The chosen materials were poly("-caprolactone), PCL, because of its slow degradation, which makes it useful for long term delivery and poly(oxyethylene-b-oxypropyleneb-oxyethylene), Lu, because of its release modulation capacity. Moreover, they are both commercially available, inexpensive and well characterised polymers. Three drugs were incorporated: timolol maleate, acetazolamide and dorzolamide hydrochloride. They are all agents that can decrease intraocular pressure (IOP) in open-angle glaucoma. Two types of devices were prepared: monolithic (sponges, bers, disks) and hybrid (disks), using supercritical solvent impregnation (SSI), electrospinning, melt compression and solvent casting. PCL blends were successfully impregnated with timolol maleate using a SSI technique. SSI e ciency results suggested that the best impregnating conditions were obtained when a cosolvent ...