Hidefumi Hayashi

Physicochemical Characterization of Parenteral Lipid Emulsion: Influence of Cosurfactants on Flocculation and Coalescence

AbstractPurpose. The stability of lipid emulsions (LE) containing various cosurfactants (oleic acid, cholesterol, Tween 80, or HCO-60) was evaluated using the maximum total interaction energy, Vtmax, and the energy barrier for coalescence, W. Methods. The Vtmax and W were calculated from the ζ potential and the rate of increase in LE particle size, respectively. Results. The Vtmax and W of LE containing the oleic acid were 0.598 × 10−19 J and 3.03 × 10−19 J, respectively, while those of LE without the cosurfactant were 0.141 × 10−19 J and 1.36 × 10−19 J. Conclusions. These findings suggest that oleic acid prevents the flocculation and coalescence of LE. The Vtmax and W of LE containing the cholesterol were 0.435 × 10−19 J and 0.63 × 10−19 J, respectively, suggesting that the cholesterol prevents the flocculation of LE but does not affect the coalescence. Analysis of the stability of LE was performed by the separate considerations of the flocculation and coalescence.

Physicochemical Characterization of Parenteral Lipid Emulsion: Determination of Hamaker Constants and Activation Energy of Coalescence

The particle size of lipid emulsion (LE) is changed by flocculation and coalescence. This change in particle size was studied using values obtained for maximum total interaction energy (Vtmax) for flocculation and activation energy for coalescence (E). Vtmax was calculated using DLVO theory, and E was calculated from the rate of increase in particle size in LE. Two LEs (PC99LE and PC70LE) were prepared from lecithins containing 99% and 70% phosphatidylcholine, respectively. The Hamaker constants for PC99LE and PC70LE were found to be 1.4 × 10−22 J and 3.1 × 10−21 J, respectively. Vtmax for PC99LE was 4.7 kT at 121°C, and E was 1.5 × 10−19 J, while Vtmax for PC70LE at 121°C was 151 kT and E was 3.2 ×10 −19 J. These findings suggest that PC99LE readily underwent flocculation and coalescence with increase in particle size, but that the particle size of PC70LE changed little. The degrees of flocculation and coalescence of LE were determined separately using values of Vtmax and E. These parameters are thus quite useful in predicting the stability of LE.

Rate of release and retentivity of prostaglandin E1 in lipid emulsion.

The rates of release of prostaglandin E1 (PGE1) from lipid particles into aqueous solution were obtained by the dialysis method, for parenteral lipid emulsion (Lipo-PGE1) diluted 10-times with buffered solutions of various pH. The findings, which were the rates of release of PGE1, were used to calculate the amount of PGE1 distributed in lipid particles when Lipo-PGE1, diluted 100-times with various pH levels of the buffered solution, was administered by intravenous drip infusion. More than 90% of PGE1 was retained in the lipid particles and intravenously infused when transfusion fluid pH was less than 5.5 and 2 ml of Lipo-PGE1 and 198 ml of transfusion fluid had been mixed and were administered over 2 h. Results from simulation showed that half of the PGE1 was retained in lipid particles and was infused, if Lipo-PGE1 was diluted 100-times with pH 8 transfusion fluid. Though PGE1 was sparingly soluble in an aqueous solution, these findings demonstrated that a significant amount of PGE1 was retained in lipid particles. Thus, this dosage form is expected to be highly effective for a drug delivery of PGE1 in clinical treatment.

In Vivo ESR Studies on Pharmacokinetics and Metabolism of Parenteral Lipid Emulsion in Living Mice

AbstractPurpose. We applied non-invasive and real-time method with in vivo ESR spectroscopy to determining pharmacokinetics and metabolism of lipid emulsion as a drug carrier in living mice. Methods. A spin-labeled triglyceride (SL-TG) was newly synthesized and lipid emulsion containing SL-TG was prepared. In vivo ESR spectra in mice were observed after intravenous administration of the lipid emulsion. Results. In vivo ESR spectra consisted of three components, coinciding with the in vitro spectra of SL-TG particles, free and immobilized fatty acids. The amount of the components depended on both the observing domain and the period after administration. In the chest, all three components were observed, while SL-TG particle was lacking in the abdomen. The half-life of the lipid particles in the chest was 2 hr. Conclusions. Non-invasive and real-time analysis of drug carriers in living animal is successfully accomplished using an in vivo ESR method.