Untitled

Abstract

Doravirine is an HIV-1 non-nucleoside reverse transcriptase inhibitor (NNRTI). The aim of the present investigation was to develop a selfnanoemulsifying drug delivery system (SNEDDS) to enhance the solubility and dissolution of poorly water-soluble doravirine. The solubility of doravirinein various oils was determined to identify the oil phase of SNEDDS. Various surfactants and co-surfactants were screened for their ability to emulsify the selected oil. A ternary phase diagram was constructed to identify the efficient self-emulsifying region. The optimized SNEDDS formulation (F8) contained drug (100 mg), neobee M5 (22.2%), caproic acid (58.2%) and PEG 600 (19.4%). The SNEDDS was further evaluated for its robustness, turbidity, % drug content, entrapment efficiency, droplet size, and zeta potential. The optimized formulation of drug-loaded SNEDDS exhibited 98% entrapment efficiency, 99% drug content and 99% in-vitro drug release in 60 min as compared with the plain drug, which had a limited dissolution rate (31%). The particle size for the optimized formulation of SNEDDS (F8) was found to be 67.8 nm with PDI 0.173. The negative value of zeta potential of -23.2 mV might be due to anionic groups of free fatty acids and glycol present in the oil, surfactant, and cosurfactant. The degradation of doravirine from optimized doravirine SNEDDS formulation was significantly less when compared to the pure drug degradation. These results suggest the potential use of SNEDDS to improve dissolution and stability of poorly water-soluble doravirine. INTRODUCTION:The oral route is the easiest and most convenient way of noninvasive administration. However, oral drug delivery may hamper drug molecules that exhibit poor aqueous solubility. Approximately 40% of the new chemical entities exhibit poor aqueous solubility and present a major challenge to the modern drug delivery system, which leads to poor oral bioavailability, high intra-, and inter-subject variability and lack of dose proportionality.