Development of Highly Stable Nifedipine Solid–Lipid Nanoparticles

Abstract

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.

Preparation and Characterization of SN-38-Encapsulated Phytantriol Cubosomes Containing α-Monoglyceride Additives

“…Nanoparticles have been used to encapsulate a wide variety of poorly water-soluble drugs, leading to dramatic improvements in their solubility, stability and drug-targeting properties, as well as reducing any adverse effects. [10][11][12][13] Furthermore, nanoparticles-based drug delivery systems can preferentially target tumors by taking advantage of the enhanced permeability and retention (EPR) effect. 14) A broad range of drug delivery systems, including PEGylated conjugates, polymer micelles, liposome formulations and dendrimers, have been extensively investigated for the formulation of SN-38 to improve its water solubility and bioavailability.…”

Effect of Alkyl Chain Length and Unsaturation of the Phospholipid on the Physicochemical Properties of Lipid Nanoparticles

“…5) NI-LNs showed excellent long-term stability in suspension for approximately 4 months in cool and dark conditions, and freeze-drying techniques combined with sugar as a cryoprotectant allowed the preparation of LNs with a good aqueous re-dispersibility. 6,7) NI-LNs lyophilized with trehalose exhibited suitable pharmacokinetic properties and good biocompatibility. 8) Generally, two types of phospholipids, neutral phosphatidylcholine (PC) and negatively-charged phosphatidylglycerol (PG) are used to prepare LNs.…”

Influences of trehalose‐modification of solid lipid nanoparticles on drug loading

“…Trehalose is usually used as a food cryoprotectant for lipid‐based drug delivery system such as liposome and SLN to prevent particles aggregation. The high concentrations of trehalose at 1–15%(w/w,%)(above m (TRE):(lipids) = 2:1) were found to be the conditions . However, according to the results presented in Table , doping trehalose into lipid matrix with low amount at [ m (TRE):(lipids) = 1:5] contributed to improvement of loading properties, indicating the stability effects of trehalose could not be interpreted only by steric stabilization provided by the cryoprotectant.…”