Osmolalities of propylene glycol-containing drug formulations for parenteral use. Should propylene glycol be used as a solvent?

Abstract

Propylene glycol (PG) is a widely used vehicle for water-insoluble drugs. Injection of drugs formulated with this solvent often results in pain, thrombosis, or thrombophlebitis that can be reduced by premedication with local anesthetics or opioids. Because osmolality and pH that are unphysiologic may cause these adverse effects, we assessed the contribution of PG to the osmolality of parenteral drug formulations. Osmolality of PG measured in distilled water showed that PG content and osmolality were directly related: 2% wt/vol PG, 264 mOsm/L; 100% PG, 15, 200 mOsm/L. The osmolalities of commercially available preparations of drugs dissolved in PG ranged from 365 mOsm/L (2% PG content) to 12,800 mOsm/L (83.46% PG), with most above 1000 mOsm/L. Replacement of PG by a solvent with lower osmolality in Germany has effectively reduced the incidence of side effects for one drug. Until PG can be replaced in drugs, we recommend diluting drugs in a large volume of saline solution; this may help to minimize the undesirable effects of this solvent.