IOLS AND DRUG IMPREGNATION

An innovative process using supercritical fluid technology can turn IOLs into sustained release drug delivery systems for steroids and antibiotics in the early postoperative weeks, said Prof Elisabeth Badens, Aix Marseille University, France. “This process can also be adapted to any polymeric matrix or implant for which a drug impregnation is required. The impregnation can also be carried out using a mixture of drugs,” she told the 18th ESCRS Winter Meeting in Ljubljana.

Prof Badens described a series of experiments in which she and her associates used carbon dioxide in supercritical conditions as a vehicle with which to impregnate commercially available PMMA rigid IOLs and foldable hydrophilic IOLs with dexamethasone and cefuroxime salts. She explained that a supercritical fluid is a compound brought to a pressure higher than its critical pressure and a temperature higher that its critical temperature. As a result it has a liquid-like density and a gas-like viscosity. “Supercritical fluids are very interesting solvents. CO2 is the most used supercritical fluid because its critical pressure is easily accessible (73.8 bar) and its critical temperature is low; it's 31°C. Therefore, so we can process thermal labile and thermal sensitive products with CO2. The supercritical CO2 impregnation is more rapid, more homogeneous and leads to a higher drug loading rate than conventional impregnation with a liquid organic phase. Moreover, it is a clean process, because we can avoid the use of organic solvents and it is suitable for liquid or solid drug solutes,” Prof Badens said. The impregnation technique involves placing the drug and IOL into two separate high-pressure vessels and pumping in CO2 until it reaches a supercritical fluid state. The CO2 causes the IOL to swell because of its polymeric nature and when the contents of two vessels mix together in a supercritical phase, the drug goes deeply into the IOL. The final step is to depressurise the vessel containing the IOL resulting in spontaneous separation of the CO2, leaving the IOL impregnated with the drug.

Using this process they have achieved variable impregnation rates but have reached rates of 10 wt per cent. However, under certain conditions they observed a foaming phenomenon during the depressurisation step, with bubbles of CO2 forming within the polymeric matrix. The foaming resulted in a marked reduction in the IOLs' transparency. Ms Badens and her associates have therefore developed a new pre-treatment step involving conditioning the IOLs in presence of pure CO2 in either a static or dynamic mode with controlled conditions of pressurisation and of depressurisation.

She noted that by using this technique they could preserve the transparency and optical properties of the lens material. In addition, they were able to show in an in vitro study that the impregnated drug passed into an aqueous-like fluid surrounding the IOLs over periods ranging from 10 and 30 days.