Abstract

Background: Tablets are conventional dosage forms in health care systems and lot of efforts are made to control the release and subsequent oral absorption of drug via sustained release matrix tablets. Different polymers, natural and synthetic, are explored in this dimension to optimize the control over drug release and absorption. Different polymers presents different response to hydration, depending upon their swelling index. This study explores the use of hydrophilic and hydrophobic natural biodegradable polymers to control the drug release and oral absorption from simple matrix tablets, without involving the complex manufacturing processes and high cost polymeric excepients.

Methods: Tizanidine HCl as model drug with low pharmacokinetic half-life was selected as cargo drug in this study. Xanthan gum and olibanum gum were used as release controlling natural hydrophilic and hydrophobic polymers with different swelling index. The underlying hypothesis was to optimize the drug release and absorption profile from matrix tablets, with different proportions of hydrophilic and hydrophobic polymers. Tablets were prepared by direct compression technique and optimized by using swelling behavior of gums upon hydration in compliance with 3² factorial models. Tablets were evaluated for in-vitro drug release, USP specifications for physical properties of tablets and oral absorption via single sample plasma Pharmacokinetics.

Results: Pre-compression and post-compression physical parameters of bulk mixture and compressed tablets were found within USP specified limits. Oral absorption study was performed in rats to develop relationship in ratios of hydrophilic/ hydrophobic gums and oral absorption of drug. Single plasma sample was collected and analyzed after 2 h of oral administration. Formulation with more proportion of hydrophilic xanthan gum showed relatively better oral absorption of drug: increased plasma level and onset of Tinazidine associated sedation in animal was observed. In-vitro release studies were carried out at pH 1.2 for first 2 h and then pH 6.8 up to 12 h. Collective higher proportion of both gums was able to sustain the drug releasing properties of tablets and both gums showed their individual effect on drug release. A percentage drug release at T25%, T50%, T90% along with mean dissolution time was determined which showed a linear relationship among all the batches.

Conclusion: Study explained the effect of relative concentration of gums with different swelling, eroding and hydration behavior-on oral absorption and controlled drug release behavior of tablets. It was concluded that both polymers worked in independent manner to optimize drug release and oral absorption.

Keywords: Erosion, matrix tablet, natural gums, oral absorption, sustained release, swelling, tizanidine HCl.