Formulation and characterization of modified release tablets containing ionizid using swellable polymers

Mf Akhtar,G Murtaza,B Akhtar,A Sharif,M Rabbani,A Saleem

doi:10.4314/ajtcam.v8i3.65286

Abstract

The aim of this work was to develop swellable modified release (MR) isoniazid tablets using different combinations of polyvinyl acetate (PVAc) and sodium-carboxymethylcellulose (Na-CMC). Granules were prepared by moist granulation technique and then compressed into tablets. In vitro release studies for 12 hr were carried out in dissolution media of varying pH i.e. pH 1.2, 4.5, 7.0 and 7.5. Tablets of all formulations were found to be of good physical quality with respect to appearance (width and thickness), content uniformity, hardness, weight variation and friability. In vitro release data showed that increasing total polymer content resulted in more retarding effect. Formulation with 35% polymer content exhibited zero order release profile and it released 35% of the drug in first hr, later on, controlled drug release was observed upto the 12(th) hour. Formulations with PVAc to Na-CMC ratio 20:80 exhibited zero order release pattern at levels of studied concentrations, which suggested that this combination can be used to formulate zero order release tablets of water soluble drugs like isoniazid. Korsmeyer-Peppas modeling of drug release showed that non-Fickian transport is the primary mechanism of isoniazid release from PVAc and Na-CMC based tablets. The value of mean dissolution time decreased with the increase in the release rate of drug clearly showing the retarding behavior of the swellable polymers. The application of a mixture of PVAc to Na-CMC in a specific ratio may be feasible to formulate zero order release tablets of water soluble drugs like isoniazid.

Highlights

Tuberculosis is a rampant infectious disease and is considered to be the foremost cause of death from a single microorganism
World Health Organization (WHO) and International Union against Tuberculosis and Lung Disease recommend the use of fixed dose combination formulations of the essential anti-tuberculosis drugs to ensure adequate treatment of patients (Blomberg et al 2001)
polyvinyl acetate (PVAc) is a water insoluble swellable polymer which has only been investigated alone and in combination with PVP in the form of Kollidon® SR (Reza et al 2003) in formulating controlled release tablets. These findings offer a potential combination of Na-CMC and PVAc to be investigated for drug release retarding properties

Summary

Introduction

Tuberculosis is a rampant infectious disease and is considered to be the foremost cause of death from a single microorganism. Of the 8 million people who actively manifest the disease, 3 million die (Hara and Hickey, 2002). Rifampicin, pyrizinamide and ethambutol were earlier prescribed as separate formulations in TB control. WHO and International Union against Tuberculosis and Lung Disease recommend the use of fixed dose combination formulations of the essential anti-tuberculosis drugs to ensure adequate treatment of patients (Blomberg et al 2001). Isoniazid is the most prescribed drug for the treatment and prophylaxis of tuberculosis. It is a highly water soluble drug and have a pKa of 7-7.5. Its bioavailability through out the intestinal tract proves it to be a strong candidate for sustained drug delivery (Mariappan and Singh, 2003)

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Results