In vitro trans-scleral iontophoresis of methylprednisolone hemisuccinate with short application time and high drug concentration

• Published in: International journal of pharmaceutics 2013-07, Vol.451 (1-2), p.12-17
• Main Authors: Pescina, S., Martini, D., Santi, P., Padula, C., Murtomäki, L., Nicoli, S.
• Format: Article
• Language: English
• Subjects: Animals; Biological Transport; Corticosteroid; Drug Delivery Systems; Glucocorticoids - administration & dosage; Glucocorticoids - pharmacokinetics; Iontophoresis; Methylprednisolone; Methylprednisolone Hemisuccinate - administration & dosage; Methylprednisolone Hemisuccinate - pharmacokinetics; Ocular delivery; Sclera - metabolism; Streaming potential; Swine; Time Factors; Trans-scleral
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2013.04.066

Trans-scleral iontophoresis, i.e. the application of small electric current to enhance drug transport across sclera is an option for non-invasive delivery of corticosteroids to the posterior segment of the eye. In this paper, in vitro trans-scleral iontophoresis of methylprednisolone hemisuccinate was investigated using concentrated drug solutions and short application times to mimic the iontophoretic conditions of in vivo studies. The drug at the donor concentration of 45mg/ml was delivered through isolated porcine sclera under passive and iontophoretic conditions (cathodal, 2.4mA) for 2–15min. In a second set of experiments, the drug was delivered for 5min at current intensities of 0.9–7.2mA. After donor removal, drug release was followed up to 24h. The exposure of concentrated solutions to sclera for 2–15min under passive conditions caused a notable accumulation of drug up to 0.8mg/cm2, the release of which was successively followed for 24h. In cathodal iontophoresis, the amount of accumulated drug increased proportionally to the charge between 0.3 and 1.44 Coulomb. When the charge was increased to 2.16 Coulomb by increasing the application time or current intensity, no further enhancement was recorded. This behaviour can be ascribed to substantial drug adsorption on the scleral tissue, as demonstrated through streaming potential studies, with the consequent increase of the electroosmotic flow that opposes drug transport. The set up suggested here could help in defining the optimal conditions for in vivo studies with animal models and reducing the number of in vivo experiments.