FORMULATION AND IN-VITRO EVALUATION OF PULSATILE RELEASE TABLETS OF RITONAVIR

The objective of the present study was to develop a time-controlled floating pulsatile drug delivery system of Ritonavir (RIT), an antiviral drug with low oral bioavailability due to degradation by CYP3A4 enzymes, efflux by P-glycoprotein, and instability at alkaline pH. Ritonavir is primarily absorbed in the stomach; hence, a floating pulsatile release system was designed to enhance absorption and therapeutic efficacy. Core tablets of Ritonavir were prepared using different superdisintegrants and evaluated for in-vitro disintegration. The disintegration time varied from 21–44 seconds, with crosspovidone showing the fastest disintegration due to rapid water penetration compared with croscarmellose sodium and sodium starch glycolate. Since rapid disintegration is critical for burst release, the F3 formulation was selected for further studies. The rapid release core tablet (F3) was compression-coated with varying concentrations of HPMC K4M, HPMC K15M, and HPMC K100M (P1–P9). Formulations with HPMC K100M (P7–P9) showed a lag time of 4–4.5 hours followed by sigmoidal release, achieving 100% drug release by 10–12 hours. Among these, P9 (core 100 mg + 180 mg HPMC K100M coating) exhibited the most desirable profile. This was further formulated with floating agents (HPMC E15LV, sodium bicarbonate, citric acid), and N2 was optimized, showing buoyancy within 1 min and sustained floatability. The final optimized batch (F3P9N2) exhibited a lag time of 4 hours with complete drug release at 12 hours and demonstrated stability under accelerated conditions without significant changes. Thus, the floating pulsatile system of Ritonavir provides a promising approach for controlled gastric retention and timed drug release.