Drug transport in HEMA conjunctival inserts containing precipitated drug particles

This paper focuses on exploring the mechanism of cyclosporine A transport in hydroxyethyl methacrylate (HEMA) rods to develop conjunctival inserts for extended ocular delivery. Cylindrical conjunctival HEMA inserts were prepared by thermal polymerization in presence of drug at high loadings to create rods containing particles of drug dispersed in the matrix. The drug release rates were measured to explore the effect of length, drug loading, crosslinking, and mixing in the release medium. Also microstructure of the inserts was characterized by SEM imaging. The inserts release the drug for a period of about a month at therapeutic rates. The rates of drug release are zero order and independent of drug loading and crosslinking for certain period of time. These effects were shown to arise due to a mass-transfer boundary layer in the fluid and a mathematical model was developed by coupling mass transfer in the insert with that in the boundary layer in the surrounding fluid. The model with diffusivity in the insert and boundary layer thickness as parameters fits the experimental data and explains all trends in release kinetics. The fitted diffusivity is about twice that obtained by direct measurements, which agreed well with the value obtained by using the Brinkman’s equation but only after accounting for drug binding to the polymer.

Conjunctival inserts has been developed to release cyclosporine A at approximately zero order for 20–25 days. Effect of drug loading, crosslinking and convection in the fluid on rate of release from inserts has been studied. An exhaustive model has been developed to predict drug release from a system/device which contain drug as particles.Figure optionsDownload high-quality image (68 K)Download as PowerPoint slide