Design and optimization of HME-based floating dolutegravir extrudates with enhanced drug release and potent anti-viral activity.

The hot-melt extrusion (HME) technique is quite successful in improving the solubility and bioavailability of poorly water-soluble drugs. Herein, we report the development of optimized dolutegravir floating systems prepared by the HME technique using Design-Expert software. Optimized parameters for floating extrudate included die temperature of 100 °C, screw speed of 58 rpm, and HPMC 15 cPs at 6% w/w, giving a floating lag time of 41 s. The extrudate showed a controlled bi-phasic drug release behavior with 93.1% drug release at 10 h, which is close to the theoretical value. FTIR, XRD, DSC, and SEM-EDS analyses revealed partial amorphization, thermal stability, and uniform drug dispersion in the polymeric matrix. Enhanced dissolution profile and gastroretention characteristics were found in vitro compared with the pure drug. The biological investigation showed improved anti-viral activity, reduced IC50 (1.2 µM vs 4.6 µM), low intracellular viral DNA, and apoptosis selectively on infected cells without any cytotoxic effects on normal cells. To the best of our knowledge, this is the first study showing the application of HME technology for gastroretentive floating systems of dolutegravir.