Abstract

Introduction: Current work involves development of a fixed dose combination (FDC) comprising of Naproxen(NAP) and Esomeprazole magnesium(EMT). Such a combination has been approved by regulatory agencies of USA, Europe, and Australia but is not yet approved in India. The approved FDC single unit system was used as reference with respect to dose and release pattern of both drugs as no multiparticulate systems are available.

Research work: For the development of FDC, the formulations of Naproxen and Esomeprazole magnesium were developed and optimized individually. Naproxen is in delayed release form in reference product and hence the target formulation had to be delayed release multiparticulate formulation. Thus, pellets and minitablets of NAP were prepared. Looking to the promising results, Minitablets were selected as core formulation. The core minitablets were delayed release coated and further film coated using Wurster processing. 

In reference FDC, EMT is formulated as immediate release formulation and hence in present study immediate release formulation of Esomeprazole was developed and optimized. Out of pellets and granules, pellets were observed to be better in terms of stability of Esomeprazole and hence was selected as final formulation.

Both the formulations were filled in suitable size of capsule as per dose of each drug. The combined formulation was then studied for drug release in multimedia and biorelevant media dissolution. In addition to this, the combined formulation was charged for stability study at long term and accelerated conditions as per ICH guidelines. .

Conclusion:The developed formulation is bioequivalent and can prove as novel formulation strategy combining minitablets and pellets into capsule which can be commercially scalable. Such a combination can improve patient compliance, reduce cost of formulation with improved efficacy as esomeprazole in immediate release form has been reported to be more effective than in delayed release form.