Hydrogel-based matrices for controlled drug delivery of etamsylate: Prediction of in-vivo plasma profiles

OBJECTIVES: To design oral controlled release (CR) hydrogel matrix tablets of etamsylate using various hydrophilic polymers. Additionally, to predict plasma concentration-time profiles of etamsylate released from different CR matrices. METHODS: Characterization of the in-vitro release rate was performed by various model dependent and model independent approaches. A simple numerical convolution strategy was adopted to predict the in-vivo performance of all matrices from their in-vitro percent released data. The statistical analysis was conducted utilizing a student t-test and ANOVA. RESULTS: The release of etamsylate from all matrices showed a deviation from Fickian transport mechanism except; F2 followed Case II release whereas, F9 and F11 obeyed Fickian diffusion. CR hydrogel based-matrices (F4 and F11) demonstrated the maximum drug retardation and satisfied the USP release limits. Concentration–time profiles of etamsylate were predicted successfully from the in-vitro release data of all prepared matrices. Pharmacokinetic parameters of etamsylate CR hydrogel matrices were significantly changed with comparison to reference product except F1. CONCLUSION: The designed (F2-F11) matrices had the capability to extend the plasma level of etamsylate for an adequate time. However, F4 and F11 were considered the most ideal formulations for once daily application of etamsylate. The prediction of in-vivo pharmacokinetics of etamsylate was very useful to assess the rationality of the designed matrices for the practical application in humans.