Development, characterization, and ex vivo evaluation of an insert for the ocular administration of progesterone

Int J Pharm. 2021 Sep 5:606:120921. doi: 10.1016/j.ijpharm.2021.120921. Epub 2021 Jul 23.

Abstract

Progesterone (PG) affords neuroprotection in degenerative diseases associated to oxidative stress, such as cataracts, age-related macular degeneration, glaucoma, diabetic retinopathy and retinitis pigmentosa. The aim of this project was to develop ocular inserts for delivery of PG to the eye. Different inserts with PG in its composition were formulated and the insert with the best characteristics (59% polyvinyl alcohol, 39% polyvinylpyrrolidone K30 and 2% propylene glycol) was selected for ex vivo studies. Physical characteristics and drug release patterns of the insert were analysed. In vitro diffusion studies revealed a controlled diffusion of progesterone. Ex vivo experiments demonstrated similar trans-corneal and trans-scleral PG diffusion (corneal apparent permeability coefficient 6.46 ± 0.38 × 10-7 cm/s and scleral apparent permeability coefficient 5.87 ± 1.18 × 10-7 cm/s; mean ± SD; n = 5). However, the amount of PG accumulated in scleras was statistically higher than in corneas (30.07 ± 9.09 μg/cm2 and 15.56 ± 4.36 μg/cm2 respectively). The PG-loaded inserts (55.6 μg/cm2) were thin, translucent, showed no irritancy (HET-CAM test) and were elastic and robust, all suitable properties for its potential use in the treatment of several ocular diseases.

Keywords: Ex vivo diffusion studies; HET-CAM assay; Ocular insert; Oxidative stress; Progesterone; Retinitis pigmentosa; Trans-corneal and trans-scleral drug delivery.

MeSH terms

  • Administration, Ophthalmic
  • Cornea
  • Drug Liberation
  • Progesterone*
  • Sclera*

Substances

  • Progesterone