Development and Characterization of a Tacrolimus/Hydroxypropyl-β-Cyclodextrin Eye Drop

Area of Science:

• Ophthalmology
• Pharmaceutics
• Drug Delivery

Background:

• Uveitis is a prevalent inflammatory eye condition with limited treatment options.
• Current treatments often involve corticosteroids, leading to the need for alternatives like tacrolimus eye drops.
• Reformulation of tacrolimus is explored to improve efficacy and safety for corticosteroid-refractory uveitis.

Purpose of the Study:

• To develop a mucoadhesive, non-toxic, and stable topical ophthalmic formulation of tacrolimus.
• To create a formulation suitable for preparation in hospital pharmacy departments.
• To evaluate the efficacy and safety of the novel tacrolimus eye drop.

Main Methods:

• Preparation of four ophthalmic formulations using tacrolimus/hydroxypropyl-β-cyclodextrin (HPβCD) inclusion complexes.
• Characterization of inclusion complex formation using phase solubility diagrams, NMR, and molecular modeling.
• Assessment of ophthalmic properties (pH, osmolality, safety), stability, ex vivo bioadhesion, and in vivo ocular permanence.

Main Results:

• Successful formation of 1:1 and 1:2 tacrolimus/HPβCD inclusion complexes.
• Achieved a 0.02% (w/v) tacrolimus concentration using 40% (w/v) HPβCD aqueous solutions.
• Formulations exhibited favorable ophthalmic properties, stability for 3 months, and significantly enhanced ocular permanence (86.2 min vs. 46.3 min) compared to the reference.

Conclusions:

• The developed mucoadhesive tacrolimus eye drops are stable, safe, and demonstrate superior ocular residence time.
• These novel eye drops represent a potential safe and effective alternative for uveitis management.
• The formulation's versatility allows for the incorporation of other drugs for topical ophthalmic administration.