Novel polysaccharides-based viscoelastic formulations for ophthalmic surgery: rheological characterization

Different formulations based on bioadhesive and biocompatible polymers, hydroxypropylmethylcellulose (HPMC), sodium hyaluronate (SH) and chitosan glutamate (CG), were prepared to be potentially used as ophthalmic viscosurgical device (OVD) during cataract surgery. Their rheological properties were analyzed in terms of flow and oscillation properties and compared to a commercially available OVD, widely employed in cataract surgery, named Viscoat. All the formulations tested presented a pseudoplastic behavior during flow. Primary systems containing HPMC or CG and HPMC/CG binary systems behaved as viscous solution (G''>G') over the range of oscillatory frequencies observed, while the primary systems containing SH and HPMC/SH binary formulations and showed an entangled network behavior when subjected to a sinusoidal stress. By increasing the SH concentration in the binary systems, the viscoelastic parameters, G'and G'', and zero frequency viscosity (derived from the Cross model) increased. Viscoat presents viscoelastic parameters values lower than the corresponding values of all the binary formulations of HPMC/SH and higher than all the formulations made up of CG and HPMC. As regard to HPMC/SH binary system, the cross-over frequency decreased by increasing SH concentration in the systems and it was the highest for Viscoat and thus the opposite occurred for the relaxation time. The rheological synergy in the binary formulations was assessed by calculating the interaction parameters which increased as a function of SH and CG concentration in the binary systems. The values of the interaction parameters of the formulations based on CG, are lower than 10 Pa indicating that they did not interact synergically while the formulations based on SH show high values of the interactions parameters (in the range from 55 to 130 Pa). This indicates that secondary bonds formation occurs between SH and HPMC. From the rheological analysis it can be concluded that the binary formulations based on CG do not possess appropriate features to be used as OVD while both the viscoelastic and the flow properties of the binary formulations made up of SH and HPMC are suitable for their application as OVD being able to maintain the ocular spaces and to be easily administrated. Moreover, thank to the adhesive properties of both components, the binary formulation should be able to interact with corneal endothelium so offering a durable protection to ocular tissue. On the basis of the rheological characterization presented in this work, we concluded that the binary system named VISC26 (HPMC at 0.8% and SH at 2.3%) represents the formulation that better fulfill the OVD requirements.