Freeze-dried nifedipine-lipid nanoparticles with long-term nano-dispersion stability after reconstitution.
Nifedipine (NI) is a poorly water-soluble drug and its oral bioavailability is very low. To improve the water solubility, NI-lipid nanoparticle suspensions were prepared by a combination of co-grinding by a roll mill and high-pressure homogenization without any organic solvent. The mean particle size and zeta potential of the NI-lipid nanoparticle suspensions were about 52.6 nm and -61.8 mV, respectively, and each parameter remained extremely constant during a period of 4 months under 6 degrees C and dark conditions, suggesting that the negative charge of the phospholipid, dipalmitoyl phosphatidylglycerol, is very effective in preventing coagulation of the particles. In order to assure the nano-order particle size of the suspensions in view of long-term stability, a freeze-drying technique was applied to the NI-lipid nanoparticle suspensions. The mean particle size of freeze-dried NI-lipid nanoparticles after reconstitution was significantly increased in comparison to that of the preparations before freeze-drying. It was found, however, that the addition of sugars (glucose, fructose, maltose or sucrose) to the suspensions before freeze-drying inhibited the aggregation of nanoparticles, suggesting that the long-term stability storage of freeze-dried NI-lipid nanoparticles after reconstitution would be overcome. In addition, freeze-dried nanoparticles with 100mg sugar (glucose, fructose, maltose or sucrose) showed excellent solubility (>80%), whereas without sugar, as a control, showed low solubility (<20%). It was found that negatively charged phospholipids and sugars prevent coagulation of NI nanoparticle suspensions, and reproduce the nanoparticle dispersion after reconstitution; and remarkably increase the apparent solubility of nifedipine.
Ohshima
Hiroyuki
H
Department of Pharmaceutical Engineering, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan.
Miyagishima
Atsuo
A
Kurita
Takurou
T
Makino
Yuji
Y
Iwao
Yasunori
Y
Sonobe
Takashi
T
Itai
Shigeru
S
D004337:Drug Carriers / Q000737:chemistry; D004355:Drug Stability; D005612:Freeze Drying / Q000379:methods*; D008055:Lipids / Q000737:chemistry; D053758:Nanoparticles / Q000737:chemistry*; D036103:Nanotechnology / Q000379:methods*; D009543:Nifedipine / Q000737:chemistry*; D010316:Particle Size; D013535:Suspensions / Q000138:chemical synthesis; D013678:Technology, Pharmaceutical / Q000379:methods
D004337:Drug Carriers; D008055:Lipids; D013535:Suspensions; D009543:Nifedipine