Stability studies of binary mixtures of haloperidol and/or midazolam with other drugs for parenteral administration.

BACKGROUND

Haloperidol and or midazolam are frequently combined with other drugs in the same solution and infused parenterally over several days to treat symptoms. The solutions may be delivered to the home well in advance of the time of administration. Consequently, physiochemical stability of these combinations needs to be studied.

OBJECTIVE

Determine the stability and physical compatibility of binary mixtures of haloperidol with morphine, scopolamine and midazolam and binary mixtures of midazolam with scopolamine and morphine.

METHODS

Mixtures of drugs were prepared under aseptic conditions in 0.9% sodium chloride or 5% glucose at concentrations used clinically for continuous infusion and stored in synthetic polyisoprenoid containers at room temperature in the presence of light for 15 days. Chemical stability was evaluated by high pressure liquid chromatography. Physical compatibility was tested by visual inspection for evidence of precipitation and color change.

RESULTS

No changes in color, precipitation of the components, or measurable losses of volume were noted. The majority of the combinations tested were stable for 15 days (T(90) >/= 15 day). However, the mixture of haloperidol and morphine reached T(90) at 10 and 9 days. The mixture containing haloperidol and scopolamine was stable for only 1 day (T(90) </= 1 day).

CONCLUSIONS

Common combinations of medications to control symptoms are compatible when mixed in 5% glucose or 0.9% sodium chloride. However, stability over 15 days is not uniform.