Effect of formulation variables on in vitro release of a water-soluble drug from chitosan–sodium alginate matrix tablets

Abstract

The objective of this study is to investigate the feasibility of using chitosan–sodium alginate (CS–SA) based matrix tablets for extended-release of highly water-soluble drugs by changing formulation variables. Using trimetazidine hydrochloride (TH) as a water-soluble model drug, influence of dissolution medium, the amount of CS–SA, the CS:SA ratio, the type of SA, the type and amount of diluents, on in vitro drug release from CS–SA based matrix tablets were studied. Drug release kinetics and release mechanisms were elucidated. In vitro release experiments were conducted in simulated gastric fluid (SGF) followed by simulated intestinal fluid (SIF). Drug release rate decreased with the increase of CS–SA amount. CS:SA ratio had only slight effect on drug release and no influence of SA type on drug release was found. On the other hand, a large amount of water-soluble diluents could modify drug release profiles. It was found that drug release kinetics showed the best fit to Higuchi equation with Fickian diffusion as the main release mechanism. In conclusion, this study demonstrated that it is possible to design extended-release tablets of water-soluble drugs using CS–SA as the matrix by optimizing formulation components, and provide better understanding about drug release from CS–SA matrix tablets.

Keywords

• Chitosan
• Sodium alginate
• Matrix tablets
• Hydrophilic matrices
• Trimetazidine hydrochloride
• Extended-release