Elaboration of sustained drug delivery intraocular lenses: comparison of an innovative process using supercritical fluids with conventional liquid route

Session Details

Session Title: IOL technology/New IOLs etc.

Session Date/Time: Saturday 13/09/2014 | 08:30-10:30

Paper Time: 08:48

Venue: Boulevard A

First Author: : E.Badens FRANCE

Co Author(s): :    O. Forzano   J. André   Y. Masmoudi   A. Bouledjouidja     

Abstract Details

Purpose:

The present work deals with the development of drug delivery intraocular lenses (IOLs) to prevent postoperative endophthalmitis in cataract surgery. Commercially available rigid and foldable IOLs were impregnated with an anti-inflammatory drug using two different processes: an innovative and clean process using supercritical carbon dioxide as the impregnation solvent and a conventional process of soaking using a mixture of water and ethanol as impregnation medium. For both impregnation methods, the impregnated IOLs act as Drug Delivery Systems (DDS). Using supercritical fluid technology, drug impregnation is significant while the transparency and optical properties are preserved. Drug is then released over days following surgery. The innovative aspect of the supercritical fluid technology is that no toxic organic solvents are used; the impregnated IOLs are then clean.

Setting:

Research laboratory of Aix Marseille University (UMR CNRS 7340), at Aix en Provence, France.

Methods:

In order to prevent postoperative infectious complications, a solution can be the use of controlled Drug Delivery Systems (DDS) placed inside the eye. If the DDS is the impregnated IOL, this solution does not require an additional act of the surgeon. Furthermore, supercritical fluid technologies have been demonstrated to be a clean and effective alternative to traditional methods of drug and polymer processing. A supercritical fluid is a compound brought at a pressure higher than its critical pressure and a temperature above its critical temperature. It has specific interesting properties such as a liquid-like density and a gas-like viscosity. Supercritical carbon dioxide (P > 7.38 MPa and T > 304.21 K) can then be used as an impregnation vehicle of the drug within the polymeric matrix of the IOLs. Commercially available rigid IOLs made from derivative of Poly (Methyl MethAcrylate) (PMMA) as well as foldable IOLs made from Poly 2-hydroxyethyl methacrylate (P-HEMA) have been impregnated with Dexamethasone 21-phosphate disodium, an anti-inflammatory drug, through a discontinuous process. The impregnation efficiency was determined in term of impregnation yield as well as in term of in-vitro drug release kinetics. The influence of some experimental operating conditions was studied by varying the pressure (8 and 20 MPa), the temperature (308 and 333 K), and by adding a co-solvent (ethanol). The influence of the IOLs dioptre was also studied (+8.0 D, +21.0 D, +30.0 D). The conventional impregnation method by soaking into a liquid phase has also been used in order to compare the two methods of impregnation. A mixture of water and ethanol (50/50 wt%) has been used as impregnation medium. The duration of soaking has been varied from 12 h to 48 h. The transparency and optical properties of IOLs have been characterized after treatment.

Results:

The drug impregnation yields vary from 0.3 to 5.3 wt % (± 0.2 %) for the rigid IOLs. Concerning the foldable IOLs, the impregnation yields vary from 2.1 to 7.9 wt % (± 0.2 %). Depending on the supercritical impregnation process conditions, a foaming phenomenon has been observed. Indeed, in presence of dense carbon dioxide, the polymeric implants plasticize. Thus, during the depressurization step, bubbles of CO2 can be formed within the polymeric matrix. The transparency properties of the resulting IOLs are then degraded. An innovative pre-treatment step has been implemented in order to avoid this foaming phenomenon. It consists in a first step of conditioning the IOLs in presence of pure CO2 either in a static or in a dynamic mode with controlled conditions of pressurization and of depressurization (between 0.01 and 1 MPa/min). Moreover, this innovative pre-treatment step ensures a reproducible state of the implant before carrying out the impregnation, allowing therefore reproducible impregnation results. In vitro drug release studies have been performed in a solution simulating the aqueous humor. The drug release is observed during a period varying from ten to thirty days depending on the impregnation conditions.

Conclusions:

An innovative process for the supercritical drug impregnation of IOLs has been implemented and appears to be the most suitable method in comparison with soaking into a liquid phase. The resulting impregnated IOLs do not contain residual organic solvent traces. They can act as Drug Delivery Systems once placed in the eyes at the end of surgery. The impregnation rates obtained are significant and the in vitro drug release studies have shown that the drug is released over a period comprised between ten and thirty days. An innovative pre-treatment step has been implemented in order to avoid the foaming phenomenon. The optical properties and the transparency of the impregnated IOLs are then preserved. Moreover, a reproducible initial state before impregnation is obtained; This process applied to IOLs 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.

Financial Interest:

NONE