The particle size distribution of emulsions containing diazepam for intravenous use

Abstract

Summary The particle size and distribution of size of emulsions intended for intravenous administration is critical for the safety of the patient owing to the dangers of embolism. However, methods of measuring the size are limited in accuracy in the micrometre and sub‐micrometre range. The use of a laser centrifugal photosedi‐mentometer (LCP) is described which is capable of detecting particles down to 002 m̈m and would appear to be eminently suitable for characterizing emulsion systems in the critical size range. The instrument has been applied to a new drug vehicle containing diazepam which is based on intravenous nutritional emulsions. This emulsion was shown to have a mean particle diameter of 0–2 m̈m, comparable with literature values for chylomicra and similar to previous experimental results on intravenous emulsions. This suggests that the drug formulation is suitable for clinical application, especially as'animal studies indicate that it has a reduced toxicity when compared to propylene glycol injection solutions.

Formulation, Characterization and Hypersensitivity Evaluation of an Intravenous Emulsion Loaded with a Paclitaxel-Cholesterol Complex

“…If the amount of oil was too low, however, it was difficult to meet the drug solubility requirements and the drug easily leak into the water phase, thereby affecting the chemical stability of the drugs. 24,25) Similar results were observed in our experiments as the particle size of the formulation with 20% LCT/MCT was smaller than that of 20% LCT, but larger than that of 10% LCT/MCT. The amounts of autoclave degradation products of the formulation with 20% LCT/MCT, 10% LCT/MCT and 20% LCT were 3.4%, 5.2% and 14.4%, respectively.…”

Bioavailability of three formulations of intravenous diazepam

“…Jeppsson and his colleagues, reporting Sato's work, noted that only particles of diameter greater than 4 pm become trapped in lung capillaries (12,13), and since the diameter of the lipid particles in Diazemuls is of the order 0.2 pm this is unlikely to explain our findings. Furthermore, the total surface area of lipid exposed to the plasma is so enormous that one would expect very rapid diffusion of the diazepam from oil to blood.…”

“…A 16 swg venous cannula was inserted into a large forearm vein, from which blood was drawn at time 0. Diazepam 10 mg was injected over a 30-9 period into a large vein in the contralateral arm, and blood was sampled at 5, 10, 15, 30, 60 and 90 min and 2, 3, 4, 5, 6, 7, 8,9,12 and 24 h. The cannula was kept patent by flushing with heparinised saline (1000 units/500 ml). Blood was centrifuged within 2 h and plasma stored at -20°C prior to batch analysis by gasliquid chromatography (6).…”