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

• Published in: Pharmaceutics Vol. 10; no. 4; p. 249
• Main Authors: Mazet, Roseline, Choisnard, Luc, Levilly, Delphine, Wouessidjewe, Denis, Gèze, Annabelle
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.12.2018; MDPI
• Subjects: Bioavailability; Chromatography; Cornea; cyclodextrins; dexamethasone acetate; dissolution assay; experimental design; eye drops; Hydrogels; Inflammation; Investigations; phase solubility; Retention; Sodium; France; United States > US; eye drops; dexamethasone acetate; dissolution assay; experimental design; hydrogels; cyclodextrins; phase solubility
• ISSN: 1999-4923; 1999-4923
• DOI: 10.3390/pharmaceutics10040249

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-β-CD (HPβCD) and hydroxypropyl-γ-CD (HPγCD) were used to enhance DXMa concentration in aqueous solution. The β and γ 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% (HPβCD) and 2% (HPγCD) DXMa with osmolality within acceptable physiological range. Finally, 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 HPβCD, more than 90% of the drug was released within 2 h, while in mixed gel containing HPγCD, the release of DXMa was partial, reaching ≈60% in 2 h. This difference will have to be further addressed with and ocular delivery experiments.