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

摘要

The goal of the present study is to develop polymeric matrix films loadedwith a combination of free diclofenac sodium (DFSfree) and DFS:Ion exchangeresin complexes (DFS:IR) for immediate and sustained release profiles,respectively. Effect of ratio of DFS and IR on the DFS:IR complexationefficiency was studied using batch processing. DFS:IR complex, DFSfree, or acombination of DFSfree+DFS:IR loaded matrix films were prepared by melt-casttechnology. DFS content was 20% w/w in these matrix films. In vitrotranscorneal permeability from the film formulations were compared against DFSsolution, using a side-by-side diffusion apparatus, over a 6 h period. Oculardisposition of DFS from the solution, films and corresponding suspensions wereevaluated in conscious New Zealand albino rabbits, 4 h and 8 h post-topicaladministration. All in vivo studies were carried out as per the University ofMississippi IACUC approved protocol. Complexation efficiency of DFS:IR wasfound to be 99% with a 1:1 ratio of DFS:IR. DFS release from DFS:IR suspensionand the film were best-fit to a Higuchi model. In vitro transcorneal flux withthe DFSfree+DFS:IR(1:1)(1 + 1) was twice that of only DFS:IR(1:1) film. Invivo, DFS solution and DFS:IR(1:1) suspension formulations were not able tomaintain therapeutic DFS levels in the aqueous humor (AH). Both DFSfree andDFSfree+DFS:IR(1:1)(3 + 1) loaded matrix films were able to achieve andmaintain high DFS concentrations in the AH, but elimination of DFS from theocular tissues was much faster with the DFSfree formulation. DFSfree+DFS:IRcombination loaded matrix films were able to deliver and maintain therapeuticDFS concentrations in the anterior ocular chamber for up to 8 h. Thus, freedrug/IR complex loaded matrix films could be a potential topical oculardelivery platform for achieving immediate and sustained releasecharacteristics.