Formation Of Poorly Water-Soluble Oral Drug Nanodispersion In Microchannel Reactor

Compared with other type of drug delivery, oral drug delivery had many advantages, such as convenience, safety, system and local treatment. However, it has been estimated about 70% of drugs were poorly water-soluble, which limited drug delivery and bioavilability. Drug nanodispersion was one of the most promising strategies to improve the bioavailability of water-insolube drugs. Controllable preparation of nanoparticles could be reached through microchannel reactor, with highly efficient micro-mixing performance and less amplification effects. In this paper, drugs nanodispersion were prepared by anti-solvent precipitation in microchannel reactor, the main content as follows:Firstly, KI-KIO3 reaction system was chosen as the chemical-probe to measure Xs of T-junction microchannel reactor and effects of operating parameters on micromixing performance were estimated. Meanwhile, resveratrol (RES) nanoparticles were also prepared in T-junction microchannel. With RES solution flow rate and anti-solvent flow rate were 3 mL/min and 60 mL/min, RES nanoparticles size was 133 nm.Secondly, preparation of RES nanodispersion were optimized through single factor experiment and orthogonal experiment. The results indicated that the size of RES nanodispersion was 95 nm. It shown that the wettability of RES had been significantly improved because of contact angle of RES nanodispersion reduced to 19°. The dissolution degree of RES nanodispersion were 88% in 120 min in the simulated human gastric juice, and 95% in 120 min in the simulated human intestinal juice.Thirdly, Silybin (SLB) nanodispersion was also prepared in T-junction microchannel reactor. With SLB solution flow rate and anti-solvent flow rate were 3 mL/min and 60 mL/min, the size of SLB nanoparticles was 77 nm. The size of SLB nanodispersion was 64 nm through optimized process conditions. SLB wettability had been significantly improved which contributed contact angle reduced to 24°. The dissolution degree of SLB nanodispersion were 81% in 120 min in the simulated human gastric juice, and 93% in 120 min in the simulated human intestinal juice.Finally, RES nanodispersion and SLB nanodispersion were prepared in tube-in-tube microchannel reactor. The size of RES nanodispersion and SLB nanodispersion were 82 nm and 38 nm, which smaller than the products prepared in T-Junction microchannel reactor. In the simulated human intestinal juice the dissolution degree of RES nanodispersion was 97% in 120 min, and the dissolution degree of SLB nanodispersion was 95% in 120 min. Contrasted with T-junction microchannel reactor throughput, the throughput of the tube-in-tube microchannel reactor was 10 times than it.