Investigation of Combined Cyclodextrin and Hydrogel Formulation for Ocular Delivery of Dexamethasone Acetate by Means of Experimental Designs.

ABSTRACT: Dexamethasone acetate (DXMa) has proven its efficiency to treat corneal inflammation, without a great propensity to increase intraocular pressure. Unfortunately, its poor aqueous solubility, associated with a rapid precorneal elimination, results in a low drug bioavailability and a low penetration after topical ocular administration. The main objective of this study was to improve the apparent aqueous solubility of DXMa using cyclodextrins. First, hydroxypropyl-?-CD (HP?CD) and hydroxypropyl-?-CD (HP?CD) were used to enhance DXMa concentration in aqueous solution. The ? and ? HPCD derivatives allowed the increase of the DXMa amount in solution at 25 °C by a factor of 500 and 1500, respectively. Second, with the aim of improving the persistence of the complex solution after instillation in the eye, the formulations of DXMa-based CD solutions with marketed ophthalmic gels (CELLUVISC®, GEL-LARMES®, and VISMED®) were investigated and optimized by means of special cubic mixture designs, allowing the defining of mixed gels loaded with 0.7% (HP?CD) and 2% (HP?CD) DXMa with osmolality within acceptable physiological range. Finally, in vitro drug release assays from the mixed gels were performed and compared with reference eye drops. Similarly to MAXIDEX® and DEXAFREE®, in the case of mixed gel containing HP?CD, more than 90% of the drug was released within 2 h, while in mixed gel containing HP?CD, the release of DXMa was partial, reaching ?60% in 2 h. This difference will have to be further addressed with ex vivo and in vivo ocular delivery experiments.

SUBMITTER: Mazet R 

PROVIDER: S-EPMC6320851 | biostudies-other | 2018 Dec

REPOSITORIES: biostudies-other