Lipid composition and structure of commercial parenteral emulsions

Férézou, Jacqueline; Lai, Nguyen-Thoi; Leray, Claude; Hajri, Tahar; Frey, Anny; Cabaret, Yvette; Courtieu, Jacques; Lutton, C.; Bach, André

doi:10.1016/0005-2760(94)90021-3

Cited by 63 publications

(50 citation statements)

References 26 publications

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“…2b). These vesicles were about 80 nm in size, which is consistent with the findings of Férézou 37) and Rotenberg. 35) Previous studies reported that liposomes show different pharmacokinetics from emulsions.…”

Section: Discussionsupporting

confidence: 91%

“…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. [35][36][37][38] Férézou et al 37) reported that the amount of liposome-like mesophase increased with the phospholipid/triacylglycerol (PL/TG) ratio. The PL/TG ratio of commercial 10, 20 and 30% fat formulas is 12, 6 and 4%, respectively.…”

Section: Discussionmentioning

confidence: 99%

“…23,39) This would be explained by difference in the affinity for a series of apolipoproteins [40][41][42][43][44][45] in blood or the subsequent metabolism by the lipoprotein lipase. 37,[46][47][48] Since it has become apparent that a considerable amount of liposome-like fractions exist in lipid emulsion suspensions, we compared the pharmacokinetics and protein binding ability of em-KW-3902 or lipo-KW-3902 with that of free-KW-3902 directly. Em-KW-3902 showed the similar pharmacokinetic profile of free-KW-3902 (Fig.…”

Section: Discussionmentioning

confidence: 99%

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

Hosokawa

Yamauchi

Yamamoto

et al. 2002

Biological & Pharmaceutical Bulletin

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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. 1) is a newly synthesized adenosine A 1 -receptor antagonist. 15,16) Recently, it was reported that KW-3902 has potent diuretic and renal protective activities in rats and dogs. [17][18][19] Additionally, KW-3902 induces a diuretic effect in various models of acute renal failure in rats 20,21) and would be expected to have therapeutic value. In a previous study, 22) we developed a lipid emulsion of KW-3902 as an injectable formulation, because KW-3902 has a solubility of less than 1 mg/ml in water.However, intravenously injected emulsions and liposomes are rapidly captured by the reticuloendothelial system (RES) in organs such as the liver and spleen. [23][24][25][26][27] This is a major barrier to the delivery of drugs to non-RES tissues, and raises the specter that lipid emulsion formulations may affect the intrinsic therapeutic profiles of agents such as KW-3902 that targets the kidney.28) However, KW-3902 shows potent diuretic and renal protective activities even as a lipid emulsion. 21,29) In the present study, we have examined the influence of dispersed systems such as lipid emulsion or liposome on the pharmacokinetic profiles of KW-3902 and its main metabolite, M1 (Fig. 1). Moreover, to define the role of the lipid emulsion on the formulation of KW-3902, we investigated in vitro the binding to blood components of KW-3902 in each formulation. MATERIALS AND METHODSMaterials KW-3902 was synthesized at Kyowa Hakko Kogyo Co., Ltd. Egg yolk lecithin (containing 99% of phosphatidylcholine), oleic acid and concentrated glycerin were purchased from NOF Corporation (Tokyo, Japan). Soybean oil was purchased from the Nisshin Oil Mills, Ltd. (Tokyo, Japan). All other chemicals were of reagent grade and obtained from Kanto Chemical Co. (Tokyo, Japan).Lipid Emulsion Table 1 shows the formulation of the lipid emulsion of KW-3902 (Em-KW-3902). The preparation was described before.22) Briefly, KW-3902 was dissolved in soybean oil and mixed with egg yolk lecithin, oleic acid, concentrated glycerin and water for injection using a high-shear homogenizer (Model PVQS-1(3), Mizuho Industrial Co., Ltd., Osaka, Japan) at 8000 rpm for 15 min at 50°C. After adjustment of the pH to 7 with 1 N NaOH, the primary emulsion was passed through a microfluidizer (Model M-110EH, Microfluidics Corp., Newton, MA, U.S.A.) 5 times at 120 MPa. The emulsion was filtrated through a 0.22 mm Ultipor filter (Pall Corp., East Hills, NY, U.S.A.), then packaged in 10 ml ampules (Type 1 glass) and sealed after nitrogen...

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

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

Hosokawa

Yamauchi

Yamamoto

et al. 2002

Biological & Pharmaceutical Bulletin

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“…The second component, with a radius of about 84 nm in all three samples, indicates the SUV. The formation of SUV in the range from 80 to 100 nm was observed in tocopherol-enriched PC liposomes [36]. For the third component, radius values of 553 nm, 334 nm and 270 nm were obtained, corresponding to samples without and with an increasing amount of α-Toc.…”

Section: Dynamic Light Scattering (Dls)mentioning

confidence: 90%

Spectroscopic studies of D-α-tocopherol concentration-induced transformation in egg phosphatidylcholne vesicles

Dwiecki¹,

Górnaś²,

Wilk

et al. 2007

Cellular and Molecular Biology Letters

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Abstract:The effects of embedding up to 60 mol% of α-tocopherol (α-Toc) on the morphology and structure of the egg phosphatidylcholine (PC) membrane were studied using spectroscopic techniques. The resulting vesicles were subjected to turbidometric and dynamic light scattering measurements to evaluate their size distribution. The α-Toc intrinsic fluorescence and its quenching was used to estimate the tocopherol position in the membrane. Optical microscopy was used to visualize morphological changes in the vesicles during the inclusion of tocopherol into the 2 mg/ml PC membrane. The incorporation of up to 15 mol% of tocopherol molecules into PC vesicles is accompanied by a linear increase in the fluorescence intensity and the simultaneous formation of larger, multilamellar vesicles. Increasing the tocopherol concentration above 20 mol% induced structural and morphological changes leading to the disappearance of micrometer-sized vesicles and the formation of small unilamellar vesicles of size ranging from 30 to 120 nm, mixed micelles and non-lamellar structures.

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“…In order to investigate the existence of liposomes (small unilamellar vesicles) due to the presence of excess S75 in addition to the triglyceride nanoparticles, 31 P-NMR spectroscopy was carried out for the nanoparticles before and after ultracentrifugation and for the supernatant layer (excess S75) (22)(23)(24). The samples (500 μl) were analyzed by high-resolution 31 P nuclear magnetic resonance (NMR) in a Bruker Avance 400 apparatus (Bruker, Karlsruhe, Germany) operating at 30°C before and after the addition of an aqueous praseodymium chloride (PrCl 3 ) solution (1 mg/ml).…”

Section: P-spectroscopy For the Donor Particlesmentioning

confidence: 99%

Comparative Study on the Suitability of Two Techniques for Measuring the Transfer of Lipophilic Drug Models from Lipid Nanoparticles to Lipophilic Acceptors

Dawoud

Hashem

2014

AAPS PharmSciTech

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Abstract. Due to their particle size in the submicrometer range, lipid nanoparticles are suitable for parenteral administration. In order to obtain information on their potential in vivo performance, a simple and effective in vitro assay to evaluate the drug release behavior of such particles is required. This study compares the use of different experimental setups for this purpose. Lipid nanoparticles from trimyristin which were loaded with fluorescent lipophilic drug models (a temoporfin and Nile red) were used as donor particles. The transfer of the two drug models to multilamellar vesicles (MLV) and emulsion droplets as lipophilic acceptor compartments was examined. The determination of the transferred substance was performed either after separation by centrifugation or by an in situ flow cytometric technique. The transfer of temoporfin was slow to the acceptor MLV and very rapid to the acceptor emulsion. With both acceptors, the transfer of temoporfin stopped at a concentration much lower than the theoretical equilibrium values. The transfer of the less lipophilic drug Nile red was very rapid to both acceptors with equilibrium concentrations close to the expected values. The transfer results of temoporfin especially to the acceptor MLV obtained with the two detection techniques were comparable while the centrifugation technique indicated an apparently higher Nile red transfer rate than the flow cytometric technique. Both techniques are equally suitable to study the transfer of temoporfin, while the flow cytometric technique is advantageous to measure the very rapid transfer of Nile red.

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Lipid composition and structure of commercial parenteral emulsions

Cited by 63 publications

References 26 publications

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

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

Spectroscopic studies of D-α-tocopherol concentration-induced transformation in egg phosphatidylcholne vesicles

Comparative Study on the Suitability of Two Techniques for Measuring the Transfer of Lipophilic Drug Models from Lipid Nanoparticles to Lipophilic Acceptors

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