Fat Emulsion as a Vechicle for Diazepam. A Study of 9492 Patients

Abstract

Conventional preparations of diazepam for i.v. use contain solvents which cause pain on injection and thrombophlebitis in a high percentage of cases. However, diazepam can be dissolved with advantage in the oleaginous phase of an oil-in-water emulsion (Diazemuls). Diazemuls has been given to 9492 patients without serious side-effects. Following i.v. injection, 2435 patients were studied with respect to pain and clinical effect. Only 0.4% experienced pain. The intended clinical effect was recorded in 99% of the patients. I.m. injection of Diazemuls resulted in a significantly smaller frequency of pain in connection with the injection than did the injection of Valium (7% and 43% respectively). Pharmacokinetic studies have been made after i.v. and i.m. injection of Diazemuls and Valium. The distribution and elimination phases after i.v. injection were the same with both forms. Thus the drug probably quickly separates from the oil particles of the emulsion after injection. After i.m. administration, the plasma concentration shows a wide spread with both preparations. A brief survey of other substances tested in emulsion form is presented.

Role of the Lipid Emulsion on an Injectable Formulation of Lipophilic KW-3902, a Newly Synthesized Adenosine A1-Receptor Antagonist.

“…Lipid emulsions have been employed as carriers for lipophilic drugs with some clinical success. 5,6,13,14) However, RES readily takes up the oil droplets of conventional lipid emulsions, [23][24][25] the carrier potentials of which are reported to be low. 34) By the way, it has been shown that the liposome-like vesicles in commercial parenteral emulsions coexist with typical oil in water emulsions in which the structure of the core oil particles coated in a lipid monolayer.…”

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Several approaches to obtaining parenteral formulations for water-insoluble or poorly soluble drugs have been reported and dispersed systems for drug delivery such as emulsions, liposomes and nanospheres are improving all the time.1-12) For instance, diazepam recently became commercially available in a lipid emulsion form, 13,14) which was developed to reduce the incidence of local side effects after intravenous injection of conventional preparations of diazepam containing organic solvents. 7 ]nonyl)-3,7-dihydro-1H-purine-2,6-dione, see Fig.

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“…1-12) For instance, diazepam recently became commercially available in a lipid emulsion form, 13,14) which was developed to reduce the incidence of local side effects after intravenous injection of conventional preparations of diazepam containing organic solvents. 7 ]nonyl)-3,7-dihydro-1H-purine-2,6-dione, see Fig.…”

Uso do remifentanil para redução da dor à injeção de propofol e a dose necessária de propofol em exames de endoscopia digestória alta diagnóstica

“…12 Isso porque o uso de emulsão lipí-dica quase aboliu a dor associada à injeção de diazepan e etomidato. [13][14][15] Formulações opcionais de propofol, com mudanças na composição da emulsão lipídica, com diferentes frações de triglicerídeos de cadeia média e longa e o uso de diferentes preservativos como o ácido etilenodiamino tetra-acético (EDTA) e o metabisulfito de sódio não eliminaram sua dor à injeção. 16 Entretanto, tem sido sugerido que o aumento do teor de lipídeos do solvente pode reduzir a concentração de propofol livre na fase aquosa e seu contato com terminações nervosas livres, o que pode reduzir a dor durante a injeção de propofol.…”

Formulation Development of a Filter-Sterilizable Lipid Emulsion for Lipophilic KW-3902, a Newly Synthesized Adenosine A1-Receptor Antagonist.

“…[9][10][11] An alternative approach for parenteral formulations of water-insoluble or poorly soluble drugs will be provided by dispersed systems, such as emulsions, [12][13][14][15][16][17][18][19] liposomes 20,21) and nanospheres, 22) which are making good progress toward more ideal DDSs. For instance, diazepam in a lipid emulsion recently became commercially available, 23,24) which was developed to reduce the incidence of local side effects after intravenous injection of conventional preparations of diazepam containing organic solvents. However, intravenously injected liposomes and emulsions are rapidly captured by the reticuloendothelial system (RES) rich organs such as the liver and spleen.…”