Characterization and evaluation in vivo of baicalin-nanocrystals prepared by an ultrasonic-homogenization-fluid bed drying method.
OBJECTIVE
To improve the absorption and bioavailability of baicalin using a nanocrystal (or nanosuspension) drug delivery system.


METHODS
A tandem, ultrasonic-homogenization-fluid bed drying technology was applied to prepare baicalin-nanocrystal dried powders, and the physicochemical properties of baicalin-nanocrystals were characterized by scanning electron microscopy, photon correlation spectroscopy, powder X-ray diffraction, physical stability, and solubility experiments. Furthermore, in situ intestine single-pass perfusion experiments and pharmacokinetics in rats were performed to make a comparison between the microcrystals of baicalin and pure baicalin in their absorption properties and bioavailability in vivo.


RESULTS
The mean particle size of baicalin-nanocrystals was 236 nm, with a polydispersity index of 0.173, and a zeta potential value of -34.8 mV, which provided a guarantee for the stability of the reconstituted nanosuspension. X-Ray diffraction results indicated that the crystallinity of baicalin was decreased through the ultrasonic-homogenization process. Physical stability experiments showed that the prepared baicalin-nanocrystals were sufficiently stable. It was shown that the solubility of baicalin in the form of nanocrystals, at 495 μg·mL(-1), was much higher than the baicalin-microcrystals and the physical mixture (135 and 86.4 μg·mL(-1), respectively). In situ intestine perfusion experiments demonstrated a clear advantage in the dissolution and absorption characteristics for baicalin-nanocrystals compared to the other formulations. In addition, after oral administration to rats, the particle size decrease from the micron to nanometer range exhibited much higher in vivo bioavailability (with the AUC(0-t) value of 206.96 ± 21.23 and 127.95 ± 14.41 mg·L(-1)·h(-1), respectively).


CONCLUSIONS
The nanocrystal drug delivery system using an ultrasonic-homogenization-fluid bed drying process is able to improve the absorption and in vivo bioavailability of baicalin, compared with pure baicalin coarse powder and micronized baicalin.
302 Military Hospital of China, Beijing 100039, China; School of Pharmaceutics, Chengdu University of Traditional Chinese Medicine, Chengdu 611730, China.
Jin
J
Shi-Ying
302 Military Hospital of China, Beijing 100039, China.
Han
H
Jin
302 Military Hospital of China, Beijing 100039, China; School of Pharmaceutics, Chengdu University of Traditional Chinese Medicine, Chengdu 611730, China.
Jin
J
Shi-Xiao
302 Military Hospital of China, Beijing 100039, China.
Lv
L
Qing-Yuan
302 Military Hospital of China, Beijing 100039, China; School of Pharmaceutics, Chengdu University of Traditional Chinese Medicine, Chengdu 611730, China.
Bai
B
Jin-Xia
302 Military Hospital of China, Beijing 100039, China.
Hong-Ge
HG
Chen
302 Military Hospital of China, Beijing 100039, China.
Li
L
Rui-Sheng
Key Laboratory of Smart Drug Delivery, Ministry of Education and PLA, School of Pharmacy, Fudan University, Shanghai, 201203 China. Electronic address: wuwei@shmu.edu.cn.
Wu
W
Wei
302 Military Hospital of China, Beijing 100039, China. Electronic address: jsypharm@126.com.
Yuan
Y
Hai-Long
D000818:Animals; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D005419:Flavonoids / Q000737:chemistry / Q000493:pharmacokinetics*; D008297:Male; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D014465:Ultrasonics; D014961:X-Ray Diffraction
D005419:Flavonoids; C038044:baicalin
Absorption; Baicalin; Bioavailability; Characterization; Nanocrystals; R283.6; Ultrasonic-homogenization-fluid bed drying