Emulsion diazepam

Mattila MA, Suurinkeroinen S, Saila K et al. (1983). Midazolam and fat-emulsion diazepam as intramuscular premedication. A double-blind clinical trial. Acta Anaesthesiol Scand, 27, 345-348. 

Sznitowska M. et al.. Bioavailability of diazepam from aqueous-organic solution, submicron emulsion and solid lipid nanoparticles after rectal administration in rabbits, Eur. J. Pharm. Biopharm., 52, 159, 2001. 

The BDZs of choice for intravenous sedation remain midazolam, diazepam (as an emulsion) and, in some European countries, flunitrazepam. These vary very little in their phamacological effects but it should be remembered that midazolam is twice as potent as diazepam and must be titrated slowly according to the patient s response. 

The administration of metabolizable vegetable oils as concentrated sources of nutrition has proved to be valuable for patients who are debilitated and who are unable to take nourishment orally. In addition, oils such as soy bean oil provide a source of essential fatty acids which can be rapidly depleted in a patient after starvation for only a few days. Wretlind and his colleagues devised the phospholipids-stabilized soy oil emulsion now marketed as Intralipid (Pharmacia, now Pfizer, New York, NY) in Sweden during the 1960s and this product has been modified to carry oil-soluble drugs such as diazepam. In Europe this is marketed as Diazemuls and it may be anticipated that other drugs may be presented in the same or similar vehicles. 

Schwarz J, Weisspapir M, Friedman D. Enhanced transdermal delivery of diazepam by submicron emulsion (SME) creams. Pharm Res 995 12 687-692. 

Levy, M.Y., Langerman, L., Gottschalk-Sabag, S., and Benita, S. (1989) Side effect evaluation of a new diazepam formulation venous sequalae reduction following i.v. injection of diazepam emulsion in rabbits.Pharm. Res., 6 510-516. 

Heparin and its salts are incompatible with many drugs including alteplase, amikacin sulfate, amiodarone hydrochloride, ampicillin sodium, aprotinin, benzylpenicillin potassium or sodium, cephalothin sodium, ciprofloxacin lactate, cytarabine, dacarbazine, daunorubicin hydrochloride, diazepam, dobutamine hydrochloride, doxorubicin hydrochloride, droperidol, erythromycin lactobionate, gentamicin sulfate, haloperidol lactate, hyaluronidase, hydrocortisone sodium succinate, kanamycin sulfate, methicillin sodium, netilmicin sulfate, some opioid analgesics, oxytetracycline hydrochloride, some phenothiazines, polymyxin B sulfate, streptomycin sulfate, tetracycline hydrochloride, tobramycin sulfate, vancomycin hydrochloride, vinblastine sulfate, cisatracurium besylate, labetalol hydrochloride, nicardipine hydrochloride, cefmetazole, sodium ions, and fat emulsion.110 112... 

The concept of using anionic nanosized emulsion vehicles for enhanced percutaneous absorption of nonsteroidal anti-inflammatory drugs (NSAIDs) and diazepam was clearly proven [189, 190], NSAIDs and diazepam in a nanosized emulsion vehicle also demonstrated noticeable systemic activity. The o/w emulsion was tested for primary irritation in humans in a 48-h trial. Low irritancy and excellent human acceptance were observed, subsequently making the further development of a nanosized emulsion vehicle very attractive. 

Sterile parenteral oil-in-water emulsions have been used extensively for over 40 years for the intravenous administration of fats, carbohydrates, and vitamins to debilitated patients. Several vegetable oil-in-water emulsions are now available commercially with droplet sizes similar to that of chylomicrons (approximately 0.5-2 pm), the natural fat droplets in the blood that transport ingested fats to the lymphatic and circulatory systems (Table 1). More recently, such emulsions have been employed as intravenous carriers for poorly water-soluble lipophilic drugs such as vitamin K (e.g.. Sterile Phytonadione Injection U.S.P.) diazepam... 

In pharmaceutical preparations, soybean oil emulsions are primarily used as a fat source in total parenteral nutrition (TPN) regimens. Although other oils, such as peanut oil, have been used for this purpose, soybean oil is now preferred because it is associated with fewer adverse reactions. Emulsions containing soybean oil have also been used as vehicles for the oral and intravenous administration of drugs drug substances that have been incorporated into such emulsions include amphotericin, " diazepam, retinoids, vitamins, poorly water-soluble steroids, fluorocarbons, and insulin. In addition, soybean oil has been used in the formulation of many drug delivery systems such as liposomes, microspheres, dry emulsions, self-emulsifying systems, and nanoemulsions and nanocapsules. ... 

Traditionally, emulsions have been used to deliver oils (castor oil, liquid paraffin) in a palatable form. This is now a minor use, but there is a growing interest in the possibility of improving delivery by the use of lipid o/w emulsions as vehicles for lipophilic dmgs (e.g. diazepam, propofol) for intravenous use. Griseofulvin, presented as an emulsion, exhibits enhanced oral absorption an emulsion of indoxole has superior bioavailability over other oral forms. Medium-chain triglycerides and mono- and diglycerides promote the absorption of ceftriaxone and cefoxitin as well as ciclosporin. 

Fat emulsions are used to supply a large amount of energy in a small volume of isotonic liquid they supply the body with essential fatty acids and triglycerides. Fat emulsions for intravenous nutrition contain vegetable oil and phospholipid emulsifier. Several commercial fat emulsions are available, such as Intralipid, Lipiphysan, Lipofundin and Lipo-fundin S. They contain either cottonseed oil or soybean oil. In Intralipid, for example, purified egg-yolk phospholipids are used as the emulsifiers, and isotonicity is obtained by the addition of sorbitol, xylitol or glycerol. Intralipid has also been used as the basis of an intravenous dmg carrier, for example for diazepam (Diazemuls) and propofol (Diprivan), as an alternative to solubilisation in nonionic micellar systems such as Cremophor EL. 

Lipid emulsion formulations of prostaglandin Ej have been used in the treatment of vascular disorders. They exhibit a reduced incidence of side-effects at the site of injection, as does the diazepam lipid emulsion. A soybean emulsion stabilized by egg-yolk lecithin releases the PGEj over a period of 4-16 hours depending on pH (Fig. 7.24). The partition coefficients of PCEj between soybean emulsion and aqueous buffers at 20°C are shovm in Fig. 7.25, explaining why... 

Levy MY, Benita S. Design and characterization of a submicronized o/w emulsion of diazepam for parenteral use. Int J Pharm 1989 54 103-112. 

Parenteral emulsions were first introduced to provide an IV source of essential fatty acids and calories. This has developed into the extensive and routine use of products such as Intraplipid, Lipofundin and Liposyn in total parenteral nutrition. There are relatively few commercially available emulsions containing active compounds the only example on the U.S. market is Diprivan Injectable Emulsion, the formulation of which is shown in Table 9.4. Diazepam is also available as an injectable emulsion on the UK market (Diazemuls ). For a more detailed discussion of the issues involved in developing parenteral emulsions, the reader is referred to Collins-Gold et al. (1990). 

An attempt was made to elucidate the rote of oleic acid in the stabilizing process of a diazepam submicron emulsion using a new approach of emulsion interface characterization. The study provided evidence that the close-packed film resulting from molecular interactions of the various film-forming components at... 

W emulsion (42.44). Von Dardel ei al. found that by administration of diazepam in an emulsion formulation, a highly significant reduction in the incidence of local vascular side effects can be achieved with no alteration in the therapeutic effect in comparison with the conventional preparative form (93). Ljungberg and Jeppsson (4) have shown in pharmacological studies that the LD i of diazepam is three times larger in the emulsion form than in the aqueous form, but there is no difference in the therapeutic effect. This caused a threefold increase in the therapeutic index in the case of the new lipid emulsion form. 

The efficacy of diazepam applied topically in emulsion creams depends greatly on the oil droplet size and to a lesser degree on the formulation composition and the oil type. Emulsions as vehicles for transdermal delivery of diazepam generate significant systemic activity of the drug as compared with conventional ointments. The efficacy of this formulation was shown to be as effective as in the range of parenteral delivery against convulsive effects induced by penta-methylenetetrazole in mice (77). 

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