<p>Preliminary I<em>n</em> V<em>ivo</em> Safety Evaluation of a Tacrolimus Eye Drop Formulation Using Hydroxypropyl Beta Cyclodextrin After Ocular Administration in NZW Rabbits</p>

Abstract

Aim: Tacrolimus is an immunosuppressive drug with higher potency compared to cyclosporine A (as a useful immunosuppressant). We prepared an ophthalmic solution formulation of Tacrolimus using hydroxypropyl beta cyclodextrin (HP-ßCD). In the present study, safety of this formulation was investigated in rabbits. Materials and Methods: Formulation containing HP-ßCD, Tacrolimus, Polyvinyl alcohol (PVA) and Benzalkonium Chloride in PBS 7.4 was prepared. Tacrolimus concentration in ophthalmic preparation was 0.05% w/v. Ten male New Zealand white rabbits were housed in clean separated cages. One drop of Tacrolimus prepared formulation and a placebo formulation were applied every 12 hrs in the right and left eyes respectively, for 28 days. Results: This new aqueous formulation of Tacrolimus could improve Tacrolimus solubility about 42 times. Clinical examinations on the 1st, 3rd, 7th, 14th and 28th days of study showed transient redness and conjunctivitis in some cases of both control and intervention groups that was not persistent. At the end of the study, there were no statistical differences between the two groups in corneal epithelial defect, redness or pathological evaluations. Conclusion: The results of this study suggest that eye drop formulation of CD-Tacrolimus is safe in preliminary evaluations and can be useful for further studies.

Cyclodextrin Stabilized Freeze-Dried Silica/Chitosan Nanoparticles for Improved Terconazole Ocular Bioavailability

“…This evidence indicates the safety and biocompatibility of terconazole-loaded SCNs as an ocular delivery system. Several studies discussed the safety of silica particles [ 78 , 79 ], chitosan HCl [ 39 , 80 , 81 ] and cyclodextrins [ 82 , 83 , 84 ] for ocular delivery. Moreover, the results reveal that the used concentrations are suitable and safe.…”

Novel Eye Drop Delivery Systems: Advance on Formulation Design Strategies Targeting Anterior and Posterior Segments of the Eye

“…After loading the KTZ-SBE-β-CD complex into in situ gels, KTZ exhibited more sustained release properties due to the diffusion of the gel, and the corneal retention and penetration of KTZ were significantly increased because of the adhesive properties of the gel [62]. Table 2 [55][56][57][63][64][65][66][67] lists cyclodextrin eye drop delivery systems in the application of the anterior and posterior segments of the eye. The patient tolerated it well, with a reduction in central macular thickness and improved vision.…”

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

“…There are several types of β-cyclodextrin (βCD) derivatives, although most of them have not been authorized or there are not enough preclinical studies to support their use at the topical ophthalmic level [ 36 ]. Some β-cyclodextrins have been used by other authors as complexing agents with several drugs [ 27 , 37 , 38 ]. The oligosaccharide 2-hydroxypropyl-β-cyclodextrin (HPβCD) is a cyclic oligosaccharide formed by seven units of α-1,4-linked glucose and a hydroxypropylated group, with a lipophilic central cavity and a hydrophilic outer surface.…”