Carboxymethylcellulose/layered double hydroxide dispersions for topical ocular delivery of non-steroidal anti-inflammatory drugs

Drug delivery to ocular tissues is mainly hindered by anatomical and physiological barriers that diminish their bioavailability. In this work, layered double hydroxides (LDHs) intercalated with non-steroidal anti-inflammatory drugs (NSAIDs; ibuprofen, ketoprofen, and ketorolac) were incorporated into carboxymethylcellulose (CMC) dispersions with the aim of adjusting their rheological properties, producing sustained release, and inducing mucoadhesive properties. Pure NSAID-intercalated LDHs (LDH-NSAID) with high drug loading were obtained. The obtained particles showed high aggregation and positive surface charges, which allowed interaction with the negatively charged groups of CMC. Isotonic 1% CMC and 1% LDH-NSAID (w/w) dispersions behaved as viscous, shear-thinning fluids, although a stronger interaction with ketoprofen led to more gel-like behavior. Also, CMC/LDH-NSAID dispersions exhibited a more sustained drug release than that achieved with analogous formulations containing pure drugs, and the modeling of the profile indicated that the release rate was mainly determined by the anion exchange of the intercalated NSAID. Finally, the formulations showed strong mucoadhesion capacity, as they produce significant changes in the zeta potential of mucin dispersions. Further optimization of the particle size and surface properties of the particles is required to modulate the release profile and to enhance the rheological properties of these CMC/LDH-based formulations.