Title: Diclofenac sodium ion exchange resin complex loaded melt cast films for sustained release ocular delivery,
Abstract: The goal of the present study is to develop polymeric matrix films loaded
with a combination of free diclofenac sodium (DFSfree) and DFS:Ion exchange
resin complexes (DFS:IR) for immediate and sustained release profiles,
respectively. Effect of ratio of DFS and IR on the DFS:IR complexation
efficiency was studied using batch processing. DFS:IR complex, DFSfree, or a
combination of DFSfree+DFS:IR loaded matrix films were prepared by melt-cast
technology. DFS content was 20% w/w in these matrix films. In vitro
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 in vivo studies were carried out as per the University of
Mississippi IACUC approved protocol. 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. In vitro transcorneal flux with
the DFSfree+DFS:IR(1:1)(1 + 1) was twice that of only DFS:IR(1:1) film. In
vivo, DFS solution and DFS:IR(1:1) suspension formulations were not able to
maintain therapeutic DFS levels in the aqueous humor (AH). Both DFSfree and
DFSfree+DFS:IR(1:1)(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 DFSfree formulation. DFSfree+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.