A green chemistry approach towards synthesizing hydrogel for sustained ocular delivery of brinzolamide: In vitro and ex vivo evaluation

Brinzolamide is a carbonic anhydrase inhibitor used in the eye drop form for the treatment of glaucoma. It requires frequent dosing to attain therapeutic concentration. Therefore, this study aimed to prepare sustained ocular drug delivery of brinzolamide. The objective of the study was to prepare a hydrogel loaded with a nanostructured lipid carrier (NLC) of brinzolamide. The hydrogel was prepared by a green synthesis approach using genipin as a natural crosslinking agent and polymers such as carboxymethyl chitosan and poloxamer 407. The melt emulsification-ultra sonication method was used to prepare a nanostructured lipid carrier of brinzolamide, which was loaded into a hydrogel using a swelling and loading method. The NLC formulation has shown small particle sizes of 111.20 ​± ​2.15 ​nm, polydispersity index of 0.280 ​± ​0.005 and % entrapment efficiency of 82.16% ​± ​0.14%. The NLC-loaded hydrogels of brinzolamide formulations were studied for swelling properties and showed temperature and pH-responsive swelling behavior. The optimized hydrogel formulation has been studied for in vitro drug release and showed drug release for a longer duration (24 ​h) than marketed eye drops (8 ​h). In an ex vivo study, hydrogel formulations showed transcorneal permeability 4.54 times greater than marketed eye drops. The hydrogel formulation of brinzolamide produced by the green synthesis method has shown sustained-release properties with no sign of ocular irritation. Hence, the hydrogel of brinzolamide-loaded NLC would be the potential drug delivery approach in the near future for sustained ocular drug delivery in glaucoma management. [Display omitted] •A green synthesis method was used to prepare a hydrogel using genipin and polymers, carboxymethyl chitosan and poloxamer 407.•Brinzolamide loaded nanostructured lipid carrier was prepared and loaded into the green synthesized hydrogel matrix.•The hydrogel formulation of brinzolamide has shown a sustained drug release than marketed eye drops.•The green synthesis approach results in hydrogel formulations with no ocular irritation.