Department of Chemical Engineering, University of Florida, Gainesville, FL 32611, United States.
Department of Chemical Engineering, University of Florida, Gainesville, FL 32611, United States.
Eur J Pharm Biopharm. 2017 Nov;120:73-79. doi: 10.1016/j.ejpb.2017.08.007. Epub 2017 Aug 18.
Cyclosporine A is prescribed for a number of ophthalmic applications such as dry eyes, uveitis in children and adolescents, vernal keratoconjunctivitis, and peripheral ulcerative keratitis. Extended release of cyclosporine from contact lenses has been explored due to the significant benefits of increased bioavailability in comparison with eye drops. Incorporation of drug loaded particles is considered to be a promising approach for increasing the drug release duration. Here we explore the feasibility of extended release of cyclosporine and possibly other hydrophobic drugs by dispersing particles that are 100% drug rather than drug loaded particles. The expected benefits are high drug loading and extended release. Specifically, we explore transport of cyclosporine in hydroxyethyl methacrylate gels for the case when the gel is loaded with high concentration of drug leading to in situ formation of particles. We explore whether we can increase the release duration from the gels by incorporation of the particles, without sacrificing light transmission which is a critical property for contact lenses. Hydrogels were prepared by free radical UV initiated polymerization with drug dissolved in the monomer solution at varying loadings. Drug release kinetics were measured from the particle loaded lenses and fitted to the Higuchi model to determine the diffusivity. The measured diffusivity is two orders of magnitude lower than estimates from Brinkman model. The differences were attributed to the high partition coefficient of about 150, which implies that a majority of the drug in the gel is bound to the polymer. The bound drug can diffuse along the surface or desorb and diffuse. The diffusivity estimates match the measured values after binding is taken into consideration. Light transmittance was measured to determine whether particle incorporation reduces the transparency. Results showed that the drug release duration could be controlled by increasing the drug loading but the transmittance was significantly reduce particularly at high drug loadings, which suggest that this approach may have limited applicability for contact lenses, but could be useful in other applications where light transmission is not critical.
环孢素 A 被用于多种眼科应用，如干眼症、儿童和青少年葡萄膜炎、春季角结膜炎和边缘溃疡性角膜炎。由于与眼药水相比，生物利用度增加带来了显著的益处，因此已经探索了从接触镜中延长环孢素的释放。将载药颗粒掺入其中被认为是增加药物释放持续时间的一种很有前途的方法。在这里，我们探索通过分散 100%药物而不是载药颗粒来延长环孢素和可能其他疏水性药物的释放的可行性。预期的好处是高药物负载和延长释放。具体来说，我们探索了当凝胶负载高浓度药物导致原位形成颗粒时，将环孢素输送到羟乙基甲基丙烯酸酯凝胶中的情况。我们探索了是否可以通过掺入颗粒来增加凝胶的释放持续时间，而不会牺牲透光率，这是接触镜的关键特性。水凝胶是通过自由基 UV 引发聚合制备的，药物溶解在单体溶液中，浓度不同。从载药镜片中测量药物释放动力学，并拟合 Higuchi 模型以确定扩散系数。测量的扩散系数比 Brinkman 模型的估计值低两个数量级。差异归因于约 150 的高分配系数，这意味着凝胶中大部分药物与聚合物结合。结合的药物可以沿着表面扩散或解吸和扩散。考虑到结合后，扩散系数估计值与测量值相符。透光率是为了确定颗粒掺入是否会降低透明度而测量的。结果表明，通过增加药物负载可以控制药物释放持续时间，但透光率会显著降低，特别是在高药物负载下，这表明这种方法对于接触镜的应用可能有限，但在透光率不是关键的其他应用中可能很有用。
