Diclofenac sodium ion exchange resin complex loaded melt cast films for sustained release ocular delivery

<p><i>Purpose</i>: The goal of the present study is to develop polymeric matrix films loaded with a combination of free diclofenac sodium (DFS<sub>free</sub>) and DFS:Ion exchange resin complexes (DFS:IR) for immediate and sustained release profiles, respectively.</p> <p><i>Methods</i>: Effect of ratio of DFS and IR on the DFS:IR complexation efficiency was studied using batch processing. DFS:IR complex, DFS<sub>free</sub>, or a combination of DFS<sub>free </sub>+<sub> </sub>DFS:IR loaded matrix films were prepared by melt-cast technology. DFS content was 20% w/w in these matrix films. <i>In vitro</i> transcorneal permeability from the film formulations were compared against DFS solution, using a side-by-side diffusion apparatus, over a 6 h period. Ocular disposition of DFS from the solution, films and corresponding suspensions were evaluated in conscious New Zealand albino rabbits, 4 h and 8 h post-topical administration. All <i>in vivo</i> studies were carried out as per the University of Mississippi IACUC approved protocol.</p> <p><i>Results</i>: Complexation efficiency of DFS:IR was found to be 99% with a 1:1 ratio of DFS:IR. DFS release from DFS:IR suspension and the film were best-fit to a Higuchi model. <i>In vitro</i> transcorneal flux with the DFS<sub>free </sub>+<sub> </sub>DFS:IR<sub>(1:1)</sub>(1 + 1) was twice that of only DFS:IR<sub>(1:1)</sub> film. <i>In vivo</i>, DFS solution and DFS:IR<sub>(1:1)</sub> suspension formulations were not able to maintain therapeutic DFS levels in the aqueous humor (AH). Both DFS<sub>free</sub> and DFS<sub>free </sub>+<sub> </sub>DFS:IR<sub>(1:1)</sub>(3 + 1) loaded matrix films were able to achieve and maintain high DFS concentrations in the AH, but elimination of DFS from the ocular tissues was much faster with the DFS<sub>free</sub> formulation.</p> <p><i>Conclusion</i>: DFS<sub>free </sub>+<sub> </sub>DFS:IR combination loaded matrix films were able to deliver and maintain therapeutic DFS concentrations in the anterior ocular chamber for up to 8 h. Thus, free drug/IR complex loaded matrix films could be a potential topical ocular delivery platform for achieving immediate and sustained release characteristics.</p>