Pharmaceutical quality evaluation of lipid emulsions containing PGE1: Alteration in the number of large particles in infusion solutions

There are two generics of a parenteral lipid emulsion of prostaglandin E1 (PGE1) (Lipo-PGE1) in addition to two innovators. It was reported the change from innovator to generic in clinical practice caused the slowing of drip rate and formation of aggregates in the infusion line. Thus, we investigated the difference of pharmaceutical quality in these Lipo-PGE1 formulations. After mixing with some infusion solutions, the mean diameter and number of large particles were determined. Although the mean diameter did not change in any infusion solutions, the number of large particles (diameter >1.0 μm) dramatically increased in generics with Hartmann's solution pH 8 or Lactec® injection with 7% sodium bicarbonate. Next, we investigated the effect of these infusion solutions on the retention rate of PGE1 in lipid particles. The retention rate of PGE1 in these two infusion solutions decreased more quickly than that in normal saline. Nevertheless, there were no significant differences among the formulations tested. Our results suggest that there is no difference between innovators and generics except in mixing with these infusion solutions. Furthermore, that monitoring the number of large particles can be an effective means of evaluating pharmaceutical interactions and/or the stability of lipid emulsions.