B. Sjostrom et al., PREPARATION OF SUBMICRON DRUG PARTICLES IN LECITHIN-STABILIZED O W EMULSIONS .2. CHARACTERIZATION OF CHOLESTERYL ACETATE PARTICLES/, International journal of pharmaceutics, 94(1-3), 1993, pp. 89-101
Submicron particles of a model drug, viz., cholesteryl acetate (CA), h
ave been characterized. The particles were prepared by precipitation o
f CA in the dispersed phase of an o/w emulsion stabilized by two diffe
rent emulsifier systems i.e., (a) a mixture of lecithin and sodium gly
cocholate and (b) a polyoxyethylene sorbitan fatty acid ester. The par
ticle size has been determined by photon correlation spectroscopy (PCS
) and transmission electron microscopy (TEM). The average particle siz
e, by number, was determined by PCS to be 21-144 nm depending on the e
mulsifier system used in the particle preparation. The smallest mean p
article size of 21 nm was achieved with a blend of lecithin and sodium
glycocholate. According to TEM pictures, the particles have a smooth
surface and are spherical, and the majority of the particles seem to b
e amorphous, exhibiting neither microporosity in the particles nor agg
regation between the particles. The transition temperature of choleste
ryl acetate in the particles prepared with the blend of lecithin and s
odium glycocholate has been determined by differential scanning calori
metry (DSC). The DSC measurements indicate that the melting point at 1
05-degrees-C of the cholesteryl acetate particles prepared with lecith
in/sodium glycocholate is lower than that of the pure macroscopic chol
esteryl acetate crystals which is 116-degrees-C. The irreversible tran
sition of cholesteryl acetate at about 80-degrees-C was not observed i
n the particle form of cholesteryl acetate prepared with the emulsifie
r blend of phosphatidyl-choline and sodium glycocholate. The suspensio
ns have also been investigated by small angle X-ray scattering (SAXS).
The cyclohexane residue in the resulting suspensions was below 25 ppm
according to analysis by gas chromatography.