Development, in vitro release and in vivo bioavailability of sustained release nateglinide tablets

Abstract Purpose The scope of this work is the characterization of the behavior of polysaccharides, such as xanthan gum, as matrix-forming agent for the development of sustained release tablets containing nateglinide. Methods Conventional immediate release (IR) and sustained release (SR) tablets were produced by wet granulation and direct compression methodologies, respectively. FTIR analysis demonstrated no interactions between drug and excipients, as the physicochemical characteristics of bulk materials were kept in the formulated tablets. Results Fresh IR and SR tablets exhibited appropriate friability and hardness properties for transport and handling. Formulations composed of xanthan gum showed delayed release properties; while dependent on the polymer concentration, release followed the first order kinetics fitting to Fickian mathematical model. The optimized formulation was tested in six male albino rats for the comparison of the in vivo performance of IR and SR tablets. While oral bioavailability remained similar between both types of tablets, the pharmacokinetic parameters demonstrated the modified release profile of SR i.e. extended half-life (t1/2) and higher maximum time to peak (tmax), and decreased maximum plasma concentration (Cmax) and elimination rate (kel), contributing for longer-term treatments with this drug. Conclusions Sustained release tablets composed of xanthan gum have been successfully developed for the oral delivery of nateglinide.