Characterisation of DM-β-cyclodextrin:prednisolone Complexes and Their Formulation As Eye Drops

Several ocular treatment options have been developed to overcome a broad range of ocular infections and corneal pathologies. Even though, commonly used ophthalmic formulations are only able to promote a short therapeutic effect, demanding a frequent dosing regimen. This study took advantage of dimethyl-β-cyclodextrin to overcome prednisolone low water solubility through complexes formation. These complexes were characterized by phase-solubility studies (Ks = 732; CE = 0.864), 1H-NMR, Differential Scanning Calorimetry and Fourier Transform Infrared Spectroscopy. Particle size distribution, prednisolone assay, rheology and osmolality were assessed to evaluate dimethyl-β-cyclodextrin and HPMC influence on the eye formulation main physicochemical properties. 1H-NMR studies showed a 1:1 molar ratio complexes’ stoichiometry; and the other physical characterisation methods (FTIR spectra and DSC thermograms) proved a successful interaction between prednisolone and dimethyl-β-cyclodextrin. Dimethyl-β-cyclodextrin promoted a statistical significative water solubility increase of drug and the particle size of all suspensions prepared presented a d90 lower than 90 μm. The presence of dimethyl-β-cyclodextrin did not change the pseudoplastic behaviour of this HPMC-based suspension, but a lower viscosity was obtained in the presence of the complexes. As the final formulation was hypotonic its osmolality was adjusted with NaCl. Overall, dimethyl-β-cyclodextrin:prednisolone complexation in the presence of hydrophilic polymer HPMC appears to be an advantageous approach for the ocular administration of this drug.