Convective loading and release of latanoprost in silicone hydrogel contact lenses

Abstract

Event Abstract Back to Event Convective loading and release of latanoprost in silicone hydrogel contact lenses William Pitt1, Ryan R. Horne1 and Kevin E. Judd1 1 Brigham Young University, Chemical Engineering Department, United States Statement of Purpose: We investigated the feasibility loading silicone hydrogel (SiHy) contact lenses with a hydrophobic anti-glaucoma drug, latanoprost, by swelling the lenses in a n-propanol solution of drug. Subsequent release into artificial tear solution (ATS) was measured. This study compares the loading and release of latanoprost in Acuvue Advance® (Johnson & Johnson Vision Care, Jacksonville, FL), Air Optix® (Alcon, Fort Worth, Texas) and Total Dailies 1® (Alcon). Methods: A 0.125 g/L n-propanol solution of radiolabeled latanoprost was made by dissolving latanoprost in n-propanol to which was added 5 µL of ethanol which contained 10 µCi of radioactive latanoprost. The loading procedure was performed at 25°C by removing a contact lens from its blister pack, rinsing with double-distilled water (DDH2O), blotting dry, immersing the contact lens in a loading solution for 240 seconds, immediately removing and washing the lens in 3 rinses for 5 seconds each in ~15 mL of DDH2O, and in ~5 mL of DDH2O for 15 minutes to allow for the lens to shrink to original size. The lens was moved either to a latanoprost extraction step or to ATS. Latanoprost extraction, a series of 2 soaks of 1 hr each in 2 mL n-propanol at 35°C, quantitated the radiolabeled latanoprost loaded into the lens, as described previously [1]. To simulating wear in ATS, the lens is immersed in 3 mL of ATS and swirled at 35°C. The lens was moved to fresh ATS after 1, 2, 4, and 6 days. A sample of ATS was taken for quantitation right before transferring the lens. Results: Latanoprost was successfully loaded into SiHy lenses. The drug showed 1st order release into artificial tears over a span of 2-3 days by which time the latanoprost was mostly depleted. For the same loading conditions, the amount of drug loaded and initial release rate were functions of the type of silicone hydrogel (see Figure 1). Of the lenses tested, Acuvue Advance® (galyfilcon A) accepted the most latanoprost and released at the fastest rates (p<0.05), followed by Air Optix® (lotrafilcon B) and Total Dailies 1® (delefilcon A) which released at similar rates. When normalized to the amount loaded, the kinetics of release of latanoprost were highly comparable for the different silicone hydrogels. Caption to Figure 1. Cumulative release of latanoprost per lens into ATS from different contact lenses . Error bars show the 95% CI, n=3. Conclusions: Literature reports of loading times for hydrophobic drugs are usually hours or days, [2] but this method allows for rapid loading of the drug latanoprost on the order of minutes. Despite a loading time of only 4 minutes, release is on the order of 2-4 days for the given conditions. We postulate that the hydrophobic character of SiHy contact lenses enables favorable interaction with the hydrophobic moieties of latanoprost, enhancing uptake during the loading process when latanoprost-solvating n-propanol in the polymer matrix is displaced by water, in which latanoprost is only minimally soluble. Loading and release was less for latanoprost than our previous findings for DMPC [1], which is consistent with latanoprost being less hydrophobic than DMPC. The amount of loading was higher in galyfilcon A which has 47% water content as compared to that of lotrafilcon B and delefilcon A, both having 33% water content. The higher loading is roughly correlated with the increase in water content of the polymer. Additional correlations of the silicone hydrogel chemistries and their potential effect on loading will also be presented. Funding for this study was provided by Brigham Young University.