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

Drug Delivery

Sai Prachetan Balguri¹  Goutham R. Adelli¹  Prakash Bhagav¹  Soumyajit Majumdar²  Vijayasankar Raman³ 

[1] Department of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, University, MS, USA;Department of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, University, MS, USA;Research Institute of Pharmaceutical Sciences, The University of Mississippi, University, MS, US;National Center for Natural Products Research, School of Pharmacy, The University of Mississippi, University, MS, USA, an;

关键词: Ion exchange resins;    immediate release formulations;    ocular drug delivery;    diclofenac sodium and polymeric matrix films;   

DOI  :  10.1080/10717544.2016.1256000

来源: Taylor & Francis

【 摘 要 】

Purpose: 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.Methods: 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.Results: 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.Conclusion: 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.

【 授权许可】

CC BY