Formulation and Characterization of Native and Crosslinked Hyaluronic Acid Microspheres for Dermal Delivery of Sodium Ascorbyl Phosphate: A Comparative Study

The present work evaluates for the first time the use of urea-crosslinked hyaluronic acid (HA-CL), a novel derivative of native hyaluronic acid (HA), to produce microspheres (MS) by emulsification-solvent evaporation, for dermal delivery of sodium ascorbyl phosphate (SAP). As the term of comparison, HA MS were prepared. A pre-formulation study-investigation of the effects of polymers solutions properties (pH, viscosity) and working conditions-led to the production of optimized HA-CL MS and HA-CL-SAP MS with: almost unimodal size distributions; mean diameter of 13.0 +/- 0.7 and 9.9 +/- 0.8 mu m, respectively; spherical shape and rough surface; high yield, similar to HA MS and HA-SAP MS (approximate to 85%). SAP was more efficiently encapsulated into HA-CL MS (78.8 +/- 2.6%) compared to HA MS (69.7 +/- 4.6%). Physical state, thermal properties, relative moisture stability of HA-CL MS and HA-CL-SAP MS were comparable to those of HA MS and HA-SAP MS. However, HA-CL-SAP MS exhibited an extended drug release compared to HA-SAP MS, despite the same kinetic mechanism-contemporaneous drug diffusion and polymer swelling/dissolution. Therefore, HA-CL formulation showed a greater potential as microcarrier (for encapsulation efficiency and release kinetic), that could be improved, in future, using suitable excipients.