Lipid emulsions stability

Meinert et al. [104-106] found that already small quantities [1 or 2% (w/v)] of partially fluorinated alkanes, C, F2 ,+ iC H2h+i, stabilize perfluorodecalin-Pluronic F68 emulsions. Riess et al. [130] deseribed a binary emulsifier system, consisting of a nonfluorinated surfactant in conjunction with a partially fluorinated alkene. Riess et al. [130] named the fluorinated amphiphile a dowel," suggesting that its fluorophilic end adsorbs in the fluorocarbon surface and its lipophilic end penetrates the lipophilic part of the egg-yolk phospholipid. The dowel, C8Fi7CH=CHCsHi7, increased the stability of a perfluorooctyl bromide (PFOB)-egg-yolk lipid emulsion stability considerably. The droplet size (0.25, m) remained constant over 9 months, even at 40 C. In the absence of the dowel, the droplet size more than doubled at 25 C to 0.49 jum. 

The benefit and necessity of adding heparin to PN are unclear. There are also concerns about the stability/compatibility of intravenous lipid emulsions with heparin added at concentrations above 1 unit/mL. Heparin should be omitted in patients with active bleeding, thrombocytopenia, heparin-induced thrombocytopenia (HIT), or heparin allergy. 

Advantages Simplified regimen for patient Increased patient compliance at home Decreased labor Decreased costs Decreased risk of contamination (due to less manipulation) Minimize infusion-related reactions from intravenous lipid emulsions Decreased vein irritation (especially with PPN) Improved stability compared to TNA Increased number of compatible medications Decreased bacterial growth compared to TNA Easier visual inspection Can use 0.22-micron bacterial retention filter Cost savings if unused (i.e. not spiked) intravenous lipid emulsion can be reused... 

Disadvantages Decreased stability compared to 2-in-1 PN Cannot use 0.22-micron bacterial retention filter Increased bacterial growth compared to 2-in-1 PN Visual inspection is difficult Limited compatibility with medications Increased labor and costs (if intravenous lipid emulsion infused separately) Increased vein irritation, especially if PPN is not coinfused with intravenous lipid emulsion... 

An excellent carrier is needed to deliver a sufficient amount of prostaglandins to the diseased site. Liposomes have been studied for a long time as possible drug carriers. However, the clinical use of liposomes has delayed because of some difficulties in mass production, sterilization, stability and safety. Since 1980 we have attempted to use lipid microspheres (lipid emulsions) instead of liposomes as a better carrier for lipophilic drugs (7). 

A reduction in the electrical charge is known to increase the flocculation and coalescence rates. Sufficient high zeta potential (> — 30 mV) ensures a stable emulsion by causing repulsion of adjacent droplets. The selection of suitable surfactants can help to optimize droplet surface charges and thus enhance emulsion stability. Lipid particles with either positive or negative surface charges are more stable and are cleared from the bloodstream more rapidly than those with neutral charge [192, 193]. 

DP Bluhm, RS Summers, MMJ Lowes, HH Durrheim. Lipid emulsion content and vitamin A stability in TPN admixtures. Int J Pharm 68 277-280, 1991. 

DF Driscoll, MN Bacon, BR Bistrian. Physicochemical stability of two types of intravenous lipid emulsion as total nutrient admixtures. J Parent Enteral Nutr 24(1) 15-22, 2000. 

As might be anticipated, on their own these materials undergo complex decomposition reactions, illustrated in the case of phospholipids used to stabilize injectable lipid emulsions. As discussed later, these systems are usually steam-sterilized so that they readily hydrolyze both in the presence of heat during the sterilization process and on subsequent storage (Figure 9.4). Oxidation reactions also occur in the presence... 

The dye l-Anilino 8-Naphthalene Sulfonic acid (ANS) has high specificity for protein. It fluoresces only when bound to protein [30]. In smears and handsections (i.e. unembedded materials) we have never observed it to effect emulsion stability in the manner more traditional protein dyes such as Coomassie Brilliant Blue or Fast Green often do. This relative pH independence probably is due to the mode of action of this dye. It becomes fluorescent in hydrophobic pockets on protein molecules [30] in contrast to the ionic bonding necessary for Fast Green FCF and Coommassie Blue [22]. We have not observed a strong cross-reaction with lipids, either, although a fluorescence of different spectral characteristics sometimes is seen. 

Nile Blue is used as a 0.01 to 0.1 %W/V aqueous solution and is simply added to or mixed with the substrate. The active component of the dye is actually a minor contaminant of the solution, not the blue-colored material [31]. The preparations are viewed with 450-490 nm excitation (an FTTC filter set. Figure 6). Emulsion stability is sometimes an issue in the presence of the cationic blue component of Nile Blue. In this case we use Nile Red, the pure form of this colorant. Nile Red solution is made fresh from a stock solution (0.1%W/V in acetone). This stock is added dropwise to water until a moderate blue color is seen and the solution is used immediately (it deteriorates quickly). For either colorant, the active molecule is fluorescent only when it is in a suitably hydrophobic environment. This usually means neutral lipid droplets [31] but other sites (aggregates of surfactants, the center of casein micelles, cutin plates in some seeds) are possibilities. 

Stability of amphotericin in lipid emulsions was moderate,910 but some researchers have reported instability of amphotericin with lipid emulsion.1112 Vigorous mixing of amphotericin and a lipid emulsion mixture has a good effect on the stability of the formulation. 

H.L. McLeod, et al., Stability of cyclosporin in dextrose 5%, NaCl 0.9% dextrose/amino acid solution, and lipid emulsion. Ann. Pharmacother. 26 172-175, 1992. 

Jumaa, M., and Muller, B. W. (1999), Physicochemical properties of chitosan-lipid emulsions and their stability during the autoclaving process, Int. J. Pharm., 183,175-184. 

Hu, M., McClements, D.J., and Decker, E.A. (2003). Lipid oxidation in com oil-in-water emulsions stabilized by casein, whey protein isolate, and soy protein isolate. J. Agric. Food Chem. 51, 1696-1700. 

Emulsifier Structure and Emulsifier Chemistry One of the key factors to successfully produce a stable lipid emulsion is the addition of a suitable emulsifier. Although a detailed discussion of emulsifiers and emulsifier chemistry is beyond the scope of this chapter, a brief introduction to emulsifiers/surfactants seems appropriate. Surfactants are surface-active compounds that can adsorb to appropriate interfaces once dispersed in a solvent (41 8). Emulsifiers are those surfactants that are specifically used to stabilize emulsions. Surfactants are... 

The DLVO theory, which was developed independently by Derjaguin and Landau and by Verwey and Overbeek to analyze quantitatively the influence of electrostatic forces on the stability of lyophobic colloidal particles, has been adapted to describe the influence of similar forces on the flocculation and stability of simple model emulsions stabilized by ionic emulsifiers. The charge on the surface of emulsion droplets arises from ionization of the hydrophilic part of the adsorbed surfactant and gives rise to electrical double layers. Theoretical equations, which were originally developed to deal with monodispersed inorganic solids of diameters less than 1 pm, have to be extensively modified when applied to even the simplest of emulsions, because the adsorbed emulsifier is of finite thickness and droplets, unlike solids, can deform and coalesce. Washington has pointed out that in lipid emulsions, an additional repulsive force not considered by the theory due to the solvent at close distances is also important. 

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