Diazepam in Emulsion Form for Intravenous Usage

VonDardel, Otto; Mebius, C.; Mossberg, Torsten

doi:10.1111/j.1399-6576.1976.tb05033.x

Cited by 54 publications

(5 citation statements)

References 5 publications

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“…Clinically, the use of diazepam in the emulsion vehicle has been investigated on a small scale (250 patient doses) by von Dardel, Mebius & Mossberg (1976). No significant difference could be demonstrated in effect when compared with Valium@ injection but there was a marked reduction of pain at the site of injection.…”

Section: Introduction *mentioning

confidence: 99%

The particle size distribution of emulsions containing diazepam for intravenous use

1976

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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.

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Section: Introduction *mentioning

confidence: 99%

The particle size distribution of emulsions containing diazepam for intravenous use

1976

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“…In a clinical investigation, VON DARDEL et al (1976) found a highly significant reduction in the incidence of adverse local vascular effects after intravenous injection of diazepam emulsion, but the pharmacokinetic properties were not investigated in this trial.…”

Section: Discussionmentioning

confidence: 91%

“…Aqueous solutions of diazepam are known to cause local damage to the vein after intravenous application (LANGDON 1973, VON DARDEL et al 1976). This can be partly reduced by using macrogoli ricinoleas (Cremophor EL) instead of propylene glycol as solubilizer, but this alternative enhances the risk of allergic manifestations.…”

Section: Discussionmentioning

confidence: 99%

Parenteral Use of Diazepam in an Emulsion Formulation. A Clinical Study

Thorn-Alquist

1977

Acta Anaesthesiol Scand

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A recently described injection formulation for diazepam, consisting of an oil emulsion where the drug is dissolved in the oil phase, has been found to give a lessened degree of side reactions than commercially available preparations. This emulsion formulation was compared to Valium inj. as premedication in patients undergoing operation for hernia or varices under epidural anaesthesia. The effects, measured as the degree of drowsiness according to an arbitrary scale, were found to be equal for the two formulations. Neither was there any difference in blood concentrations in the two application groups, respectively, between the preparations used. The propylene glycol content of Valium inj. is said to cause a delayed release of the drug from the injection site after i.m. application, and this is briefly discussed, as well as the possibility of administering the diazepam emulsion continuously, diluted with Intralipid, without the risk of precipitation.

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“…Diazepam (Von Dardel et al 1976, erythromycin (Marlin et al 1983) and clarithromycin (Lovell et al 1994;Cannon et al 1995) have also been known to cause pain on injection. There may be several possible reasons for this, including precipitation of drug at the site of injection, contamination of the solution with foreign particles (Cannon et al 1995), and the hypo-or hyperosmolarity of the drug solution (Klement & Arndt 1991).…”

Section: Introductionmentioning

confidence: 99%

“…The oil-in-water emulsion system has been shown to be eOE ective in reducing the pain response on injection by encapsulating drugs, such as diazepam and propranolol (Von Dardel et al 1976Doenicke et al 1996). Furthermore, the encapsulation of poorly water-soluble drugs in the emulsion system can provide a formulation with improved drug solubility (Strickley & Anderson 1993;Park & Kim 1999;Perkins et al 2000).…”

Section: Introductionmentioning

confidence: 99%

Microemulsion formulation of clonixic acid: solubility enhancement and pain reduction

Lee

Park

Lim

et al. 2002

Journal of Pharmacy and Pharmacology

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Clonixic acid is currently marketed as a salt form because of its poor water-solubility. However, the commercial dosage form causes severe pain after intramuscular or intravenous injection. To improve the solubility of clonixic acid and to reduce pain on injection, clonixic acid was incorporated into oil-in-water microemulsions prepared from pre-microemulsion concentrate composed of varying ratios of oil and surfactant mixture. As an oil phase for drug incorporation, up to 14% castor oil could be included in the pre-microemulsion concentrate without a significant increase in droplet size. Both drug contents and droplet size increased as the weight ratio of Tween 20 to Tween 85 decreased. Taken together, when microemulsions were prepared from pre-microemulsion concentrate composed of 5:12:18 weight ratio of castor oil:Tween 20:Tween 85, clonixic acid could be incorporated at 3.2 mg mL(-1) in the microemulsion with a droplet size of less than 120 nm. The osmotic pressure of this microemulsion was remarkably lower than the commercial formulation, irrespective of the dilution ratios. The rat paw-lick test was used to compare pain responses among formulations. The microemulsion formulation significantly reduced the number of rats licking their paws as well as the total licking time, suggesting less pain induction by the microemulsion formulation. The pharmacokinetic parameters of clonixic acid after intravenous administration of the clonixic acid microemulsion to rats were not significantly different from those of the commercial formulation, lysine clonixinate. The present study suggests that microemulsion is an alternative formulation for clonixic acid with improved characteristics.

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Diazepam in Emulsion Form for Intravenous Usage

Cited by 54 publications

References 5 publications

The particle size distribution of emulsions containing diazepam for intravenous use

The particle size distribution of emulsions containing diazepam for intravenous use

Parenteral Use of Diazepam in an Emulsion Formulation. A Clinical Study

Microemulsion formulation of clonixic acid: solubility enhancement and pain reduction

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