Thiol modification of galactoarabinan and its appraisal as controlled release carrier of sofosbuvir

Abstract

The study shows the development and optimization of thiolated and unthiolated polymer as a carrier of sofos- buvir, an anti-hepatic drug for sustained release. Successful thiolation was confirmed by the appearance of peak at 2518 cm− 1 in FTIR and 9.07 mg of thiol group per gram of polymer (found by Ellmans reagent test). The decrease in the moisture content in thiolated polymer by Karl Fischer titration also confirmed the modification of polymer. The unthiolated and thiolated polymer was characterized by Fourier-transform infrared spectroscopy, scanning electron microscopy and thermal analysis, and evaluated for in vitro dissolution release studies and in vivo pharmacokinetics. Pre-formulation and post-formulation tests for tablets were performed. Thiolated (15% and 20%) and unthiolated (15%) polymer possessed excellent flow properties whereas; thiolated polymer (25%) showed sustained release of drug for 4 h in in vitro dissolution profile. Moreover, pharmacokinetic parameters including Cmax, tmax, t1/2 and AUC were determined after administering standard oral solution (SOS) and tablets of sofosbuvir at a single oral dose of 42 mg/kg body weight. Results of in vivo pharmacokinetics (p < 0.0001) have explored that Cmax increased from 503 ng/ml (SOS) to 591 and 653 ng/ml for F and TF ng/ml, tmax from less than an hour (SOS) to 5hrs. The t1/2 was increased from 1hr (SOS) to 5.15 and 7 h for F and TF and observed average AUC was 2104, 5616.5, 7199 ng/ml/hr for standard, F and TF respectively. The observed Area under the curve (AUC) for all three formulations was significantly different (p > 0.05), indicating the noticeable influence of the polymer and its modified form. Based on this study, it can be concluded that thiolated polymer formulation has exhibited sustained release of sofosbuvir with improved pharmacokinetic profile.