Supercooled smectic nanoparticles: a potential novel carrier system for poorly water soluble drugs.
OBJECTIVE
The possibility of preparing nanoparticles in the supercooled thermotropic liquid crystalline state from cholesterol esters with saturated acyl chains as well as the incorporation of model drugs into the dispersions was investigated using cholesteryl myristate (CM) as a model cholesterol ester.


METHODS
Nanoparticles were prepared by high-pressure melt homogenization or solvent evaporation using phospholipids, phospholipid/ bile salt, or polyvinyl alcohol as emulsifiers. The physicochemical state and phase behavior of the particles was characterized by particle size measurements (photon correlation spectroscopy, laser diffraction with polarization intensity differential scattering), differential scanning calorimetry, X-ray diffraction, and electron and polarizing light microscopy. The viscosity of the isotropic and liquid crystalline phases of CM in the bulk was investigated in dependence on temperature and shear rate by rotational viscometry.


RESULTS
CM nanoparticies can be obtained in the smectic phase and retained in this state for at least 12 months when stored at 230C in optimized systems. The recrystallization tendency of CM in the dispersions strongly depends on the stabilizer system and the particle size. Stable drug-loaded smectic nanoparticles were obtained after incorporation of 10% (related to CM) ibuprofen, miconazole, etomidate, and 1% progesterone.


CONCLUSIONS
Due to their liquid crystalline state, colloidal smectic nanoparticles offer interesting possibilities as carrier system for lipophilic drugs. CM nanoparticles are suitable model systems for studying the crystallization behavior and investigating the influence of various parameters for the development of smectic nanoparticles resistant against recrystallization upon storage.
Kuntsche
J
J
Friedrich-Schiller-University Jena, Institute of Pharmacy, Department of Pharmaceutical Technology, D-07743 Jena, Germany.
Westesen
K
K
Drechsler
M
M
Koch
M H J
MH
Bunjes
H
H
D002152:Calorimetry, Differential Scanning; D002788:Cholesterol Esters / Q000737:chemistry; D003080:Cold Temperature; D004337:Drug Carriers; D005079:Excipients; D005614:Freeze Fracturing; D007834:Lasers; D008859:Microscopy, Polarization; D008863:Microspheres; D010316:Particle Size; D004364:Pharmaceutical Preparations / Q000008:administration & dosage* / Q000737:chemistry; D012212:Rheology; D012995:Solubility; D012997:Solvents; D014783:Viscosity; D014961:X-Ray Diffraction
D002788:Cholesterol Esters; D004337:Drug Carriers; D005079:Excipients; D004364:Pharmaceutical Preparations; D012997:Solvents; C032561:cholesteryl myristate