Formulation optimization of andrographolide self-nanoemulsifying drug delivery system and effect of precipitation inhibitor on its phase behavior / 中草药

ABSTRACT

Objective: To investigate the effect of HPMC, PVP k30 and PEG 4000 on the phase behavior of andrographolide self-nanoemulsifying drug delivery system (AG-SNEDDS) dispersed in Fasted-state simulated intestinal fluid (FaSSIF). Methods: The preparation technology of andrographolide AG-SNEDDS was optimized by central composite design. The effect of three types of precipitation inhibitors (PVP-k30, HPMC, PEG 4000) on the supersaturation behavior of AG-SNEDDS dispersed in FaSSIF was investigated with the degree of supersaturation as an evaluation index. The precipitated phase was evaluated by polarized light microscopy (PLM). Results: The results showed that the best prescription of AG-SNEDDS was Capryol 90-Cremophor EL:Tween-20 (1:1)-Transcutol HP (12.9:40.5:46.6). The self-microemulsion was uniform, the drug loading was (6.93 ± 0.04) mg/g. The emulsification time was (22.33 ± 0.33) s, the average particle size was (14.25 ± 0.65) nm. HPMC and PEG 4000 can maintain the supersaturation of AG-SNEDDS after being dispersed in FaSSIF, and the effect was positively correlated with their concentration. As for PVP k30, it reduced the degree of supersaturation at a low concentration, but can maintain supersaturation at medium and high concentration. Using any of the three precipitation inhibitors can reduce the particle size of the precipitated particles. Conclusion: Precipitation inhibitors can maintain the supersaturation of AG when disperse AG-SNEDDS in FaSSIF. The ability to maintain supersaturation varies with the types and concentration of precipitation inhibitor.