Avoiding crystallization of lorazepam during infusion.
Lorazepam is a strong sedative for intensive care patients and a commonly used method of administering it to the patient is by infusion of a freshly prepared lorazepam solution. During lorazepam infusion often unwanted lorazepam crystallization occurs, resulting in line obstruction and reduced lorazepam concentrations. With the aid of solubility measurements a solid-liquid phase diagram for lorazepam in mixtures of a commercially available lorazepam solution and an aqueous glucose solution was determined. This confirmed that the glucose solution acts as an anti-solvent, greatly reducing the lorazepam solubility in the infusion solution. Three approaches are proposed to obtain stable lorazepam solutions upon mixing both solutions and thus to prevent crystallization during infusion: (1) using a high lorazepam concentration, and thus a lower glucose solution volume fraction, in the mixed solution; (2) using an elevated temperature during solution preparation and administration; (3) reducing the lorazepam concentration in the commercial lorazepam solution.
Dept. of Multi-Scale Physics, Delft University of Technology, The Netherlands.
J
J
Vellema
N G M
NG
Hunfeld
H E A
HE
Van den Akker
J H
JH
ter Horst
D003460:Crystallization; D005947:Glucose / Q000737:chemistry*; D006358:Hot Temperature; D006993:Hypnotics and Sedatives / Q000737:chemistry*; D007262:Infusions, Intravenous; D007552:Isotonic Solutions / Q000737:chemistry*; D008140:Lorazepam / Q000737:chemistry*; D012995:Solubility; D013594:Syringes
D006993:Hypnotics and Sedatives; D007552:Isotonic Solutions; D005947:Glucose; D008140:Lorazepam