Development of Sustain Release Matrix Tablet of Ranolazine Based on Methocel K4M CR: In Vitro Drug Release and Kinetic Approach.

ABSTRACT

In this study an attempt was made to design and evaluate oral sustained release matrix tablets of ranolazine using Methocel K4M CR as the retardant polymer. Tablets were prepared by conventional wet granulation technique. Tablets were evaluated for parameters such as weight variation, hardness, friability and drug content. All the formulations showed compliance with pharmacopieal standards. In vitro release studies were performed using USP type II apparatus (paddle method) in 900 mL of 0.1N HCl at 50 rpm for 8 hours. The release kinetics was analyzed using the zero-order, first order, Higuchi, Hixson-Crowell and Korsmeyer-Peppas equations to explore and explain the mechanism of drug release from the matrix tablets. In vitro release studies revealed that percent drug release decreased with increase of polymer loading. Based on the dissolution data comparison with innovator brand F-5 formulation (16% Methocel K4M CR w/w of drug) was elected as the best formulation. The drug release profile of the best formulation was well controlled and uniform throughout the dissolution studies. The drug release of optimized formulation follows the Higuchi kinetic model (R2 = 0.99) and the mechanism is found to be non-Fickian/anomalous according to Korsmeyer–Peppas equation. All the formulations were checked for stability as per ICH guidelines and formulations were found stable during the study.