Abstract
Background: Glimepiride (GLM) is widely used for the treatment of type -II diabetes mellitus, one of the third generation sulfonylurea drugs having poor aqueous solubility, low oral bioavailability, and low elimination half life. Hence to improve its bioavailability, biodegradable chitosan nanoparticles containing GLM was developed.
Methods: GLM loaded chitosan nanoparticles were prepared by ionic gelation method using 3-factor, 3- level Box-Behnken design. Response Surface Methodology (RSM) was used to optimize the independent variables like Polymer concentration (chitosan), Surfactant concentration (Tween 80) and cross linking agent (TPP) on dependent variables like Encapsulation Efficiency (EE) and in vitro drug release (DR). The developed GLM loaded chitosan nanoparticle were characterized for FTIR, DSC, XRD and Particle size.
Result: The result of the RSM analysis shows that Chitosan and Tween 80 was significant for the EE (p < 0.0001) and DR (p<0.0001), whereas TPP is only significant for the EE (p = 0.0015). Statistical and Mathematical analysis of the design shows linear model was significant with correlation factor value (R2) of 0.9956 and 0.9925 to evaluate the EE and DR, respectively. The EE increases and DR decreases with increase in concentration of chitosan and was found in the range of 46.23% to 101.2%. In vitro drug release of GLM loaded chitosan nanoparticle shows sustained release up to 24 hours.
Conclusion: From the study, we can conclude that response surface methodology seems to be promising approach for improving the oral bioavailability leading to improve patient compliance.
Keywords: Box-Behnken design, bioavailability, chitosan, diabetes mellitus, glimepiride, chitosan.
Graphical Abstract
17
1