A polymeric aqueous tacrolimus formulation for topical ocular delivery.

Tacrolimus (TAC) suspension is used to treat moderate to severe atopic keratoconjunctivitis (AKC) and vernal keratoconjunctivitis (VKC). The objectives of this study were to formulate the hydrophobic compound TAC (TAC) in an aqueous eye drop formulation and study its ocular biodistribution on topical ocular application to a healthy rabbit model, with the overall aim of using the formulation to treat AKC and VKC. A thin-film hydration method was used to encapsulate TAC within the chitosan-based amphiphile: N-palmitoyl-N-monomethyl-N,N-dimethyl-N,N,N-trimethyl-6-O-glycolchitosan (Molecular Envelope Technology - MET) in an aqueous formulation. The formulation was characterized, and its stability studied under three storage conditions for one month. The ocular distribution of the formulation was studied in healthy rabbits and the ocular tissues and the whole blood analyzed by LC-MS/MS. A 200 nm nanoparticle formulation (MET-TAC) containing 0.1 ± 0.002% w/v TAC was produced with viscosity, osmolarity and pH within the ocular comfort range, and the formulation was stable on refrigeration for one month. On topical application, the TAC concentrations in rabbit cornea and conjunctiva one hour after dosing were 4452 ± 2289 and 516 ± 180 ng/g of tissue, respectively. A topical ocular aqueous TAC eye drop formulation has been prepared with the ability to deliver sufficient drug to the relevant ocular surface tissues.