Article

Projet
Outils de formulation et de vectorisation de substances actives  
Denis WOUESSIDJEWEAnnabelle GEZELuc CHOISNARDDelphine LEVILLY,   
Titre
Investigation of Combined Cyclodextrin and Hydrogel Formulation for Ocular Delivery of Dexamethasone Acetate by Means of Experimental Designs  
Auteurs
Roseline Mazet , Luc Choisnard , Delphine Levilly , Denis Wouessidjewe and Annabelle Gèze
Edition
Pharmaceutics, 2018 , 10 , 249
Année
2018
Résumé
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 γHPCD 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, in vitro drug release assays from the mixed gels were performed and compared with reference eye drops. Similarly to MAXIDEX® and DEXAFRE ®, in the case of mixed gel containing HPβCD, more than 90% of the drug was released within 2 h, while in mixed gel containing HPγ CD, the release of DXMa was partial, reaching≈60% in 2 h. This difference will have to be further addressed withex vivo andin vivo ocular delivery experiments. (16) (PDF) Investigation of Combined Cyclodextrin and Hydrogel Formulation for Ocular Delivery of Dexamethasone Acetate by Means of Experimental Designs. Available from: https://www.researchgate.net/publication/329379140_Investigation_of_Combined_Cyclodextrin_and_Hydrogel_Formulation_for_Ocular_Delivery_of_Dexamethasone_Acetate_by_Means_of_Experimental_Designs