Lysis of human red blood cells 2: effect of contact time on cosolvent induced hemolysis

Krzyzaniak, Joseph F.; Raymond, Dawn M.; Yalkowsky, Samuel H.

doi:10.1016/s0378-5173(97)00082-3

Cited by 44 publications

(50 citation statements)

References 6 publications

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“…Although the developed composition is probably toxicologically adequate, because it contains fewer excipients than the similarly formulated and marketed medications, it was the aim of the present work to further decrease the amount of excipients and still be able to solubilize the therapeutically effective dose of miconazole. It is important to do this because numerous papers deal with the toxicity of the excipients used in this study and all come to a similar conclusion, stating that lower level of excipient results in a lower level of toxicity (1,(29)(30)(31). Toxic effects of surfactants are associated with their interaction with biological membranes, and as such are proven to exert hemolytic effect (32).…”

Section: Optimizing the Concentration Of Excipientsmentioning

confidence: 77%

“…In contrast, where the solubilizing power of the composition is below the theoretical solubility of the diluted composition (dilution line), precipitation may occur. Precipitation does not necessarily occur in these cases, since other factors, such as supersaturation and nucleation determine whether the APIs actually precipitate or not (30). The data show that a composition equivalent to a formulation comprising 0.1% polysorbate, 20% ethanol, and ammonium acetate (pH 3.1) diluted with dextrose or sodium chloride infusions (tenfold dilution) results in a composition exerting lower solubilizing capacity than that which would be needed to stop miconazole from precipitating (since the solubility curve falls below the dilution line).…”

Section: Solvent System For Miconazolementioning

confidence: 99%

“…In the case of liquid formulations comprising one or more active ingredients which show poor water solubility, solubility enhancers are often used to ensure the therapeutically effective dose of the compounds (3)(4)(5)(6)(7)(8)(9). The effect of such excipients on the pharmacokinetics of the drugs and their impact on the blood have been widely studied (10)(11)(12)(13) and although the toxicity of a formulation can by no means be explained solely by the concentration of the applied excipients, it is widely accepted that the lower the level of an excipient in a formulation, the less likely it is to induce toxicity. An inappropriate amount or composition of solvents can cause hemolysis, precipitation of the drug, phlebitis, and pain (14)(15)(16)(17).…”

Section: Introductionmentioning

confidence: 99%

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Composition Optimization and Stability Testing of a Parenteral Antifungal Solution based on a Ternary Solvent System

et al. 2010

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Abstract. An intravenous solution is a dosage forms intended for administration into the bloodstream. This route is the most rapid and the most bioavailable method of getting drugs into systemic circulation, and therefore it is also the most liable to cause adverse effects. In order to reduce the possibility of side effects and to ensure adequate clinical dosage of the formulation, the primarily formulated composition should be optimized. It is also important that the composition should retain its therapeutic effectiveness and safety throughout the shelf-life of the product. This paper focuses on the optimization and stability testing of a parenteral solution containing miconazole and ketoconazole solubilized with a ternary solvent system as model drugs. Optimization of the solvent system was performed based on assessing the risk/ benefit ratio of the composition and its properties upon dilution. Stability tests were conducted based on the EMEA (European Medicines Agency) "guideline on stability testing: stability testing of existing active substances and related finished products". Experiments show that both the amount of co-solvent and surface active agent of the solvent system could substantially be reduced, while still maintaining adequate solubilizing power. It is also shown that the choice of various containers affects the stability of the compositions. It was concluded that by assessing the risk/benefit ratio of solubilizing power versus toxicity, the concentration of excipients could be considerably decreased while still showing a powerful solubilizing effect. It was also shown that a pharmaceutically acceptable shelf-life could be assigned to the composition, indicating good long-term stability.

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Section: Optimizing the Concentration Of Excipientsmentioning

confidence: 77%

Section: Solvent System For Miconazolementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Composition Optimization and Stability Testing of a Parenteral Antifungal Solution based on a Ternary Solvent System

et al. 2010

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“…It has been demonstrated that commonly employed parenteral cosurfactants such as glycerol or propylene glycol can cause considerable hemolysis on long term contact with the blood (36,37). Identification of hemolytic potential of a parenteral microemulsion is necessary especial- a Data were expressed as mean±SD (n=3).…”

Section: In Vitro Hemolysismentioning

confidence: 99%

Design and Evaluation of Microemulsions for Improved Parenteral Delivery of Propofol

Date

Nagarsenker

2008

AAPS PharmSciTech

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Abstract. The objective of this investigation was to evaluate the potential of the microemulsions to improve the parenteral delivery of propofol. Pseudo-ternary phase diagrams were plotted to identify microemulsification region of propofol. The propofol microemulsions were evaluated for globule size, physical and chemical stability, osmolarity, in vitro hemolysis, pain caused by injection using rat paw-lick test and in vivo anesthetic activity. The microemulsions exhibited globule size less than 25 nm and demonstrated good physical and chemical stability. Propofol microemulsions were slightly hypertonic and resulted in less than 1% hemolysis after 2 h of storage with human blood at 37°C. Rat paw-lick test indicated that propofol microemulsions were significantly less painful as compared to the marketed propofol formulation. The anesthetic activity of the microemulsions was similar to the marketed propofol formulation indicating that they do not compromise the pharmacological action of propofol. The stability studies indicated that the microemulsions were stable for 3 months when stored at 5±3°C. Thus, microemulsions appeared to be an interesting alternative to the current propofol formulations.

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“…To remove plasma and mononuclear cells a previously described protocol was applied using a separation fluid (Lymphoprep 1.077, AxisShield, PoC AS, Oslo, Norway) (24). One ml of packed erythrocytes was added to 74 ml distilled water and gently shaken for 10 min to induce 100% haemolysis (25). The homogenate was centrifuged (4,000 rpm, RT, 15 min) and the supernatant was assayed for arginase-1.…”

Section: Arginase-1 Concentration In Erythrocytesmentioning

confidence: 99%

Elevated plasma arginase-1 does not affect plasma arginine in patients undergoing liver resection

et al. 2008

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Arginine is an important substrate in health and disease. It is a commonly held view that arginase-1 release from injured erythrocytes and hepatocytes leads to arginine breakdown; however, the true relationship between plasma arginase-1 concentration and activity has remained unaddressed. In the present study, blood was sampled from patients undergoing liver resection, a known cause of hepatocyte injury and arginase-1 release, to determine arginase-1, arginine and ornithine plasma levels. Arginase activity was assessed in vitro by measuring changes in arginine and ornithine plasma levels during incubation of plasma and whole-blood samples at 37 °C. Arginase-1 plasma levels increased 8–10-fold during liver resection, whereas arginine and ornithine levels remained unchanged. In accordance with these in vivo findings, arginine and ornithine levels remained unchanged in plasma incubated at 37 °C irrespective of the arginase-1 concentration. In contrast, arginine plasma levels in whole blood decreased significantly during incubation, with ornithine increasing stoichiometrically. These changes were irrespective of arginase-1 plasma levels and were explained by arginase activity present in intact erythrocytes. Next, plasma samples with 1000-fold normal arginase-1 concentrations were obtained from patients undergoing cadaveric liver transplantation. A significant decrease in arginine plasma levels occurred in vivo and in vitro. In contrast with commonly held views, moderately increased arginase-1 plasma levels do not affect plasma arginine. Very high plasma arginase-1 levels are required to induce potential clinically relevant effects.

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Lysis of human red blood cells 2: effect of contact time on cosolvent induced hemolysis

Cited by 44 publications

References 6 publications

Composition Optimization and Stability Testing of a Parenteral Antifungal Solution based on a Ternary Solvent System

Composition Optimization and Stability Testing of a Parenteral Antifungal Solution based on a Ternary Solvent System

Design and Evaluation of Microemulsions for Improved Parenteral Delivery of Propofol

Elevated plasma arginase-1 does not affect plasma arginine in patients undergoing liver resection

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