The preparation and evaluation of water-soluble SKLB610 nanosuspensions with improved bioavailability.
The aim of the study was to investigate the potential of nanosuspension to enhance the bioavailability of SKLB610 (Biopharmaceutical Classification System class II drug), a bioactive anticancer compound synthesized in our labs. SKLB610 nanosuspensions were prepared using wet media milling. Physicochemical characteristics of the nanosuspensions were evaluated, including particle size and distribution, dissolution, transmission electron microscopy, atomic force microscopy, thermogravimetric analysis, and X-ray powder diffractometry. The dissolution rate of SKLB610 was greatly improved in nanosuspensions, compared to crude SKLB610. Pharmacokinetic studies in rats demonstrated that the oral bioavailability of SKLB610 in nanosuspension (89.4%) was 2.6-fold higher than in coarse suspension (34.1%). Stabilizer type, milling time, and milling speed had a significant effect on particle size of the SKLB610 nanosuspensions. Nanosuspensions effectively improved the dissolution rate and bioavailability of the water-insoluble drug SKLB610 by reducing the compound particle size to the nanoscale and employing a proper formulation.
State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, 610041, China.
Yunchuang
Y
Huang
Xun
X
Luo
Xinyu
X
You
Yong
Y
Xia
Xuejiao
X
Song
Luoting
L
Yu
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000493:pharmacokinetics*; D001549:Benzamides / Q000737:chemistry* / Q000493:pharmacokinetics*; D001682:Biological Availability; D008297:Male; D018625:Microscopy, Atomic Force; D046529:Microscopy, Electron, Transmission; D010316:Particle Size; D010848:Picolinic Acids / Q000737:chemistry* / Q000493:pharmacokinetics*; D033362:Powder Diffraction; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D014867:Water / Q000737:chemistry
D000970:Antineoplastic Agents; D001549:Benzamides; C587623:N-methyl-4-(4-(3-(trifluoromethyl)benzamido)phenoxy)picolinamide; D010848:Picolinic Acids; D014867:Water