Preparation of stable nitrendipine nanosuspensions using the precipitation-ultrasonication method for enhancement of dissolution and oral bioavailability.
The aim of this study was to prepare and characterize nitrendipine nanosuspensions to enhance the dissolution rate and oral bioavailability of this drug. Nanosuspensions were prepared by the precipitation-ultrasonication method. The effects of five important process parameters, i.e. the concentration of PVA in the anti-solvent, the concentration of nitrendipine in the organic phase, the precipitation temperature, the power input and the time length of ultrasonication on the particle size of nanosuspensions were investigated systematically, and the optimal values were 0.15%, 30 mg/ml, below 3 degrees C, 400 W and 15 min, respectively. The particle size and zeta potential of nanocrystals were 209 nm (+/- 9 nm) and -13.9 mV (+/-1.9 mV), respectively. The morphology of nanocrystals was found to be flaky in shape by scanning electron microscopy (SEM) observation. The X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC) analysis indicated that there was no substantial crystalline change in the nanocrystals compared with raw crystals. The in vitro dissolution rate of nitrendipine was significantly increased by reducing the particle size. The in vivo test demonstrated that the C(max) and AUC(0-->12) values of nanosuspension in rats were approximately 6.1-fold and 5.0-fold greater than that of commercial tablets, respectively.
Xia
Dengning
D
Department of Pharmaceutics, School of Pharmaceutical Science, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang 110016, China.
Quan
Peng
P
Piao
Hongze
H
Piao
Hongyu
H
Sun
Shaoping
S
Yin
Yongmei
Y
Cui
Fude
F
D000818:Animals; D001682:Biological Availability; D002121:Calcium Channel Blockers / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics*; D011232:Chemical Precipitation; D004339:Drug Compounding / Q000379:methods; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry; D008297:Male; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D036103:Nanotechnology / Q000379:methods*; D009568:Nitrendipine / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics*; D009994:Osmolar Concentration; D010316:Particle Size; D011142:Polyvinyl Alcohol / Q000737:chemistry; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D013535:Suspensions; D013696:Temperature; D013997:Time Factors; D014465:Ultrasonics
D002121:Calcium Channel Blockers; D005079:Excipients; D013535:Suspensions; D011142:Polyvinyl Alcohol; D009568:Nitrendipine