Drug delivery function of DDSs in clinical use: Changes in phase-distribution of PGE₁ in lipid emulsions after dilution with aqueous infusions

To guarantee the drug delivery function of the DDS drugs in clinical use, supplementary information closely related to the diverse clinical usage is required in addition to information listed on the Products Information. Changes in the phase-distribution of PGE₁ in lipo-PGE₁(Palux inj. and Liple ®), a targeting-type DDS, after 10-times dilution with 6 aqueous infusions frequently prescribed for clinical treatment, i. e., 5% Otsuka Toueki (Glucose Injection JP), Otsuka Seisholcuchu (Isotonic Sodium Chioride Solution JP), Klinit ® (Xylitol Injection JP), Physiosol ®·3, Hartmann's Solution pH : 8 and Intralipos ® 10%, were examined in vitro. Total amounts of PGE₁ and the amounts of PGE₁ in the aqueous phase were determined by the ultrafiltration method to estimate phase-distribution ratios of PGE₁ after 10-times dilution. Total amounts of PGE1 did not decrease after the dilution with each aqueous infusion. The amount of PGE₁ in the lipid emulsion phase decreased from 87% to 75, 72, 61, 47 and 20% after the dilution with Physiosol ®·3, 5% Otsuka Toueki, Klinit ®, Otsuka Seishokuchu and Hartmann's Solution pH : 8, respectively, but not with Intralipos ® 10%. The release of PGE₁ from the lipid emulsions occurred in relatively short period of time after the dilution and the phase-distribution ratios of PGE₁ were unchanged throughout the experiment for 6 h. These findings strongly suggest that the dilution with Hartmann's Solution pH : 8 and Isotonic Sodium Chloride Solution is not necessarily the recommended prescriptions for combination with lipo-PGE₁in maintaining its drug delivery function by the pharmaceutical view points. High pH of aqueous infusion combined with lipo-PGE₁ for dilution tends to increase the release.