Formulation and In-vivo Evaluation of Nanosponges Based Tramadol HCL C/R Tablets Using Design of Experiment

The current study was aimed to develop a controlled release formulation of tramadol utilizing the cyclodextrin based nanosponges. Box-Behnken design was employed to study the effect of each independent variable on dependent variables. Five types of nanosponges from β-cyclodextrin (NS1-NS5) were purposely designed. The prepared nanosponges by freeze drying method were characterized and formulated into tablets and evaluated for in-vitro and in-vivo studies. The particle sizes of tramadol-nanosponges are in between 34.38 to 134.26 nm, encapsulation efficiency of 41.13-86.72% and drug release% at 6h of 52.34-81.12%. More than 90 % of drug was found to be released from nanosponge formulations. The FTIR, DSC and XRPD studies confirmed the interaction of Tramadol with nanosponges. The nanosponges Cmax of 915.24±1.67 ng/ml was significantly higher (p<0.05) than the marketed product's Cmax of 411.5±1.25 ng/ml. Both the nanosponges formulation and the commercial product had Tmax values of 1.5±0.06 and 2.0±0.05 hours, respectively. When compared to the marketed product (342.6±0.65 ng h/ml), the AUC0-t of the nanosponges formulation (643.2±0.56 ng h/ml) was substantially greater (p<0.05) indicating better systemic drug absorption from nanosponges formulation. Cyclodextrin based nanosponges showed enhanced solubility with increased bioavailability of poorly soluble Tramadol for controlled drug delivery