Development of highly stable nifedipine solid-lipid nanoparticles.
To improve the solubility of the drug nifedipine (NI), highly stabilized solid-lipid nanoparticles (SLNs) of nifedipine (NI-SLNs) were prepared by high pressure homogenization using two phospholipids, followed by lyophilization with individual sugar moieties (four monosaccharides and four disaccharides). The mean particle diameter, polydispersity index (PDI), zeta potential, drug loading, and the encapsulation efficiency of the NI-SLN suspension were determined to be 68.5 nm, 0.3, -62.1 mV, 2.7%, and 97.5%, respectively. In comparison with the NI-SLNs, the NI-SLNs lyophilized with trehalose (NI-SLN-Tre) showed a slight increase in the particle size from 68.5 to 107.7 nm, but the PDI decreased from 0.38 to 0.33, and no significant change in zeta potential was observed. Aqueous re-dispersibility study demonstrated that NI-SLNs lyophilized with trehalose had the maximum concentration (14.7 µg/mL) at 5 min, compared with lyophilized SLNs using other sugars; the use of other sugars also resulted in significant changes in the particle size, PDI, and zeta potential. A trehalose concentration of 2.5% w/v and a two-fold dilution of the SLN suspension were found to be the best conditions for lyophilization. Data from lyophilized SLNs using differential scanning calorimetry, powder X-ray diffraction, Fourier-transform infrared spectroscopy, and scanning electron microscopy indicated eventual transformation of NI-SLN-Tre from a crystalline to an amorphous state during the homogenization process. Finally, a stability study was performed with NI-SLN-Tre for up to 6 months at 30°C and 65% relative humidity, with no significant deterioration observed, suggesting that trehalose might be a useful cryoprotectant for NI-SLNs.
Department of Pharmaceutical Engineering and Drug Delivery Science, School of Pharmaceutical Sciences, University of Shizuoka.
Ranjan Kumar
RK
Barman
Yasunori
Y
Iwao
Yuka
Y
Funakoshi
Abdul-Hackam
AH
Ranneh
Shuji
S
Noguchi
Mir Imam Ibne
MI
Wahed
Shigeru
S
Itai
D015195:Drug Design; D053758:Nanoparticles / Q000737:chemistry*; D009543:Nifedipine / Q000737:chemistry*; D010316:Particle Size; D010743:Phospholipids / Q000737:chemistry*; D013499:Surface Properties; D013997:Time Factors
D010743:Phospholipids; D009543:Nifedipine