Abstract

DESIGN, OPTIMIZATION, FORMULATION AND EVALUATION OF SUSTAINED RELEASE MATRIX TABLETS OF MONTELUKAST SODIUM

*R. Natarajan, S. K. M. Jananipriya, S. Jayaseelan and V. Ganesan

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Abstract

Montelukast sodium is a Leukotriene receptor antagonist used for the maintenance treatment of Asthma and to relieve symptoms of seasonal allergies and it’s a BCS class II drug with half-life of 2.7 to 5.5 hrs. Mean oral bioavailability is about 64%. The objective of this study was to develop the Sustained release matrix tablets of Montelukast sodium by Direct Compression method using various polymers such as Xanthan gum, Ethyl cellulose and Eudragit RSPO in various concentrations. The drug excipient mixtures were subjected to preformulation studies. FTIR study was shown there was no interaction between drug and polymers. Optimization was carried out using Stat- Ease software. A randomized 23 full factorial design was selected. Based on Central composite design the polymers concentration should be optimized. The formulation F1 to F9, the polymer ratio was optimized as low and high level with QbD. The tablets were subjected to physicochemical evaluation, in vitro drug release, kinetic and stability studies. The physicochemical properties of tablets were found within the limits. And all the formulations (F1to F9) shows the drug release between 89.92% and 93.89%. The optimized formulation F10 showed maximum drug release of 95.49% at the end of 12hrs. The drug release kinetic data confirmed that all the formulation (F1 to F10) fit in Higuchi model which shows the highest R2 value of 0.966 to 0.995. The results of in vitro release data were fitted to the Korsmeyer Peppa’s equation to analyse pattern of the drug release from polymeric system. The slope (n) value was found between 0.539 – 0.682, indicating that the drug release follows non-Fickian release mechanism. It can be concluded that combination of Eudragit RSPO with other polymer (F10) shows stable and better duration of release rate, when compared to individual polymer.

Keywords: Montelukast sodium, Xanthan gum, Ethyl cellulose, Eudragit RSPO, Optimized-(F10), QbD, Sustained release, Higuchi model, Non-Fickian release.