Abstract

DESIGN, DEVELOPMENT AND CHARACTERIZATION OF ZIDOVUDINE SUSTAINED RELEASE MATRIX TABLETS

K. Sumana*. Someswara Rao, Suresh V. Kulkarni

ABSTRACT

Sustained release formulation of zidovudine based on monolithic - matrix technology was developed and evaluated. Zidovudine is watersoluble drug so it is suitable to develop sustained release matrix tablet. Zidovudine is a short acting drug, so developed formulation provides the advantages of sustained release formulations. Zidovudine is a first potent antiviral agent used in the treatment of AIDS. Zidovudine is rapidly absorbed from the gastrointestinal tract, with peak serum levels achieved with in about one hour. Oral sustained release matrix tablets of zidovudine were prepared by dry granulation technique using hydroxyl propyl methyl cellulose polymer (HPMC) different grades. Hydroxyl propyl methyl cellulose polymer (HPMC) is water soluble and rate controlling polymer. The effect of the concentration of the polymer was studied. The studies indicated that the drug release can be modulated by varying the concentration of the polymer. Granules were prepared and evaluated for loose bulk density, tapped bulk density, compressibility index and angle of repose, shows satisfactory results. Formulation was optimized on the basis of acceptable tablet properties (hardness, friability, drug content and weight variations) and in-vitro drug release. The resulting formulation produced robust tablets with optimum hardness, consistent weight uniformity and low friability. Release kinetics was evaluated by using United States Pharmacopeia (USP)-22 type II dissolution apparatus. The in vitro release study of matrix tablets were carried out in purified water for 12 hours. Among all the formulations, F-3 shows 96.52% release at the end of 12 hours. The results indicated that a decrease in release kinetics of the drug was observed by increasing the polymer concentration. The release data was fitted to various mathematical models such as, Higuchi, Korsmeyer-Peppas, First-order, and Zero-order to evaluate the kinetics and mechanism of the drug release. Kinetic modeling of in-vitro dissolution profiles revealed the release mechanism ranges from diffusion controlled or quasi-Fickian transport to anomalous type or non-Fickian transport, which was only dependent on the type and amount of polymer used. The drug release follows first order kinetics and the mechanism was found to be diffusion coupled with erosion. The stability studies were carried out according to ICH guideline which indicates that the selected formulations were stable.

Keywords: Zidovudine, Hydoxy propyl methyl cellulose, Matrix tablets, dry granulation, sustained release.