Parenteral emulsions

Intravenous aqueous injections provide an excellent means of achieving a rapid therapeutic response. Parenteral product design, eg, vehicle and other excipient selection, as well as choice of route of adrninistration, can prolong therapeutic activity and increase onset times. Thus, oily solutions, suspensions, or emulsions can be adrninistered by subcutaneous or intramuscular routes to create prolonged effect, ie, depot injection (28). 

When normal enteral feeding in not possible or is inadequate to meet an individual s nutritional needs, intravenous (IV) nutritional therapy or total parenteral nutrition (TPN) is required. Products used to meet the IV nutritional requirements of the patient include protein substrates (amino acids), energy substrates (dextrose and fat emulsions), fluids, electrolytes, and trace minerals (see the Summary Drug Table Electrolytes). 

PN should provide a balanced nutritional intake, including macronutrients, micronutrients, and fluid. Macronutrients, including amino acids, dextrose, and intravenous lipid emulsions, are important sources of structural and energy-yielding substrates. A balanced PN formulation includes 10% to 20% of total daily calories from amino acids, 50% to 60% of total daily calories from dextrose, and 20% to 30% of total daily calories from intravenous lipid emulsion. Micronutrients, including electrolytes, vitamins, and trace elements, are required to support essential biochemical reactions. Parenteral... 

Iron-deficiency anemia in chronic PN patients may be due to underlying clinical conditions and the lack of iron supplementation in PN. Parenteral iron therapy becomes necessary in iron-deficient patients who cannot absorb or tolerate oral iron. Parenteral iron should be used with caution owing to infusion-related adverse effects. A test dose of 25 mg of iron dextran should be administered first, and the patient should be monitored for adverse effects for at least 60 minutes. Intravenous iron dextran then may be added to lipid-free PN at a daily dose of 100 mg until the total iron dose is given. Iron dextran is not compatible with intravenous lipid emulsions at therapeutic doses and can cause oiling out of the emulsion. Other parenteral iron formulations (e.g., iron sucrose and ferric gluconate) have not been evaluated for compounding in PN and should not be added to PN formulations. 

During the past 30 years, there have been significant developments of parenteral disperse formulations. The use of parenteral emulsions can overcome the problems of low aqueous solubility and water hydrolysis of many drugs [184, 185]. Such formulations can avoid the use of conventional co-solvent systems and the undesirable effects caused by precipitation of drugs at the injection site. Recent developments of parenteral disperse formulations have the potential to provide sustained release and targeting of drugs [186-189],... 

Like all parenteral products, parenteral emulsions are required to be sterile, isotonic, nonpyrogenic, nontoxic,... 

Emulsifiers. Natural lecithin is one of the most widely used emulsifiers because it is metabolized in the body. However, type I allergic reaction to soybean lecithin emulsified in lipid solutions has been observed [195], Among the synthetic emulsifying agents, block copolymers of polyoxyethylene-polyoxypropylene (poloxamer) have attracted increasing interest for parenteral emulsions. Other examples of emulsifiers commonly found in parenteral formulations are given in Table 9 [190]. 

Table 9 Most Commonly Used Emulsifiers in Parenteral Emulsions...

Autoclaving can be used for the sterilization of parenteral emulsions, provided the required sterilization conditions do not lead to significant product degradation. Alternatively, parenteral emulsions can be... 

S Harnisch, RH Muller. Adsorption kinetics of plasma proteins on oil-in-water emulsions for parenteral nutrition. Eur J Pharm Biopharm 49(l) 41-46, 2000. 

AG Floyd. Top ten considerations in the development of parenteral emulsions. Pharm Sci Tech Today 2(4) 134-143, 1999. 

VS Koster, PFM Kuks, R Langer, H Talsma. Particle size in parenteral fat emulsions, what are the true limitations Int J Pharm 134 235-238, 1996. 

M Jumaa, BW Muller. The effect of oil components and homogenization conditions on the physicochemical properties and stability of parenteral fat emulsions. Int J Pharm 163(1—2) 81—89, 1998. 

Large-volume parenterals 101 and larger Venoclysis Solutions and some emulsions Nearly all drug classes (see... 

A surfactant is a surface-active agent that is used to disperse a water-insoluble drug as a colloidal dispersion. Surfactants are used for wetting and to prevent crystal growth in a suspension. Surfactants are used quite extensively in parenteral suspensions for wetting powders and to provide acceptable syringability. They are also used in emulsions and for solubilizing steroids and fat-soluble vitamins. 

For parenteral emulsions, the formulation scientist must be particularly aware of changes in particle size distribution of the oil phase. Droplet coalescence results in increased droplet size. As a general rule, average droplet size should be less than 1 pm. Droplet sizes of more than 6 pm can cause blockage of capillaries (capillary emboli). 

Although this chapter is directed toward ophthalmic products, it is largely applicable to parenteral and even nonsterile products (solutions, emulsions, and suspensions). The choice of preservative is limited to only a few chemicals that have been found, over the years, to be safe and effective for this purpose. These are benzalkonium chloride, thimerosal, methyl- and propylparaben, phenylethanol, chlorhexidine,... 

Aqueous products that are at greatest risk from microbial spoilage include solutions, suspensions, and emulsions for repeated oral, parenteral, or external use and include critical products such as multidose injections and eye drops. Unpreserved products without adequate antimicrobial efficacy should not be presented in containers intended for use on more than one occasion unless justified. When antimicrobial preservatives are used, their efficacy has to be demonstrated using the Ph Eur test for antimicrobial preservative efficacy. Factors to be taken into account in designing a preserved product include the nature of the preservative, its concentration in the product, the... 

For parenteral products specific consideration needs to be included for tonicity adjustment, emulsion globule size, ease of resuspension and sedimentation rate, particle size and particle size distribution, viscosity and syringeability, and crystal form changes. Full consideration should be included of the proposed instructions for dilution or reconstitution of products and of compatibility with the proposed solvents or diluents. This should include a demonstration that the proposed storage temperature and extremes of concentration are suitable. 

J du Plessis, LR Tiedt, AF Kotze, CJ van Wyk, C Ackerman. A transmission electron microscope method for determination of droplet size in parenteral fat emulsions using negative staining. Int J Pharm 46, 1988. 

Fat-emulgated preparations for parenteral administration have been elaborated for clinical applications. Since these are administered to the patients intravenously, the size of fat emulsion particles should not exceed the size of the largest naturally occurring lipoproteins-chylomicrons, i.e. about I fiin. Fat emulsions on the basis of com oil (preparation lipomaize), cottonseed oil (lipofundin, lipomol). 

Aik Phos, alkaline phosphatase ALT, alanine aminotransferase (SCPT) AST, aspartate aminotransferase (SGOT) Bili, bilirubin EFAD, essential fatty acid deficiency IVFE, intravenous fat emulsion PN, parenteral nutrition. 

Parenteral dose forms include aqueous, aqueous organic, and oily solutions, emulsions, suspensions, and solid forms for implantation. These parenterals need to be sterile and pyrogen-free they are, if possible, buffered close to normal physiological pH and preferably are isotonic with the body fluids. 

Lundberg BB, et al. A lipophilic paclitaxel derivative incorporated in a lipid emulsion for parenteral administration. J Control Release 2003 86 93. 

Parenteral suspensions (injection) Exact dose 100% compliance Suitable for unconscious patient Rapid onset, especially after intravenous administration Painful Self-administration vmusual Requires trained personnel Solutions, emulsions, implants Expensive production processes... 

Category I la. Injections, other parenterals including emulsions, otic, sterile nasal products, and ophthalmic products made with aqueous bases or vehicles... 

The fat emulsion used to solubilise propofol is similar to Intralipid, used for parenteral nutrition. Its disadvantages include (1) being an excellent culture medium if bacterially contaminated and (2) presenting the patient with a... 

Parenteral 0.5 mg/mL emulsion for injection Diltiazem (generic, Cardizem)... 

Lipid emulsions are essential components of parenteral nutrition. However, due to the amount of polyunsaturated fatty acids (PUFA), it is possible that chemical degradation occurs, forming hydroperoxides. 

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