RESUMO
PURPOSE: The objective of this study was to improve the absorption behavior of N-251, a novel antimalarial drug, by preparing an appropriate self-nanoemulsifying drug delivery system (SNEDDS). METHODS: Two different types of SNEDDS formulations, medium-chain fatty acid-based SNEDDS (MC-SNEDDS) and long-chain fatty acid-based SNEDDS (LC-SNEDDS), were prepared based on pseudo-ternary phase diagram, and examined for their in vivo oral absorption behavior in rats. RESULTS: Oral dosing of MC-SNEDDS formulations significantly improved the bioavailability (BA) of N-251 compared with N-251 powders. However, its high hepatic extraction limited the BA of N-251 to only 0.49 for MC-SNEDDS B, the best formulation of MC-SNEDDS. LC-SNEDDS formulations, especially LC-SNEDDS F provided the highest BA, 0.65, and successfully attenuated the inter-individual difference in the absorption behavior. Furthermore, it was confirmed that lymphatic transport of N-251 for LC-SNEDDS F was significantly increased up to around 3.19 times larger than that for MC-SNEDDS B. Simulation study suggested that 20 to 39% of N-251 uptaken by the small intestine would be delivered to lymphatic system after oral administration of LC-SNEDDS F. CONCLUSIONS: SNEDDS formulations significantly improved the absorption behavior of N-251 and long-chain fatty acid-based lipid further improved it by avoiding the hepatic first-pass elimination.
Assuntos
Antimaláricos/farmacocinética , Ácidos Graxos/química , Sistema Linfático/metabolismo , Compostos de Espiro/farmacocinética , Tetraoxanos/farmacocinética , Animais , Antimaláricos/administração & dosagem , Disponibilidade Biológica , Química Farmacêutica , Sistemas de Liberação de Medicamentos , Excipientes , Absorção Intestinal , Fígado/metabolismo , Masculino , Ratos , Ratos Wistar , Solubilidade , Compostos de Espiro/administração & dosagem , Tetraoxanos/administração & dosagemRESUMO
Shock waves were explored in the thermoacoustic spontaneous gas oscillations occurring in a gas column with a steep temperature gradient. The results show that a periodic shock occurs in the traveling wave mode in a looped tube but not in the standing wave mode in a resonator. Measurements of the harmonic components of the acoustic intensity reveal a clear difference between them. The temperature gradient acts as an acoustic energy source for the harmonic components of the shock wave in the traveling wave mode but as an acoustic energy sink of the second harmonic in the standing wave mode.
