In vitro hemolysis: Guidance for the pharmaceutical scientist

Amin, Ketan; Dannenfelser, Rose‐Marie

doi:10.1002/jps.20627

Cited by 283 publications

(191 citation statements)

References 3 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 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: Introductionmentioning

confidence: 99%

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

et al. 2010

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“…The test was conducted according to the literature. 35 The human RBCs were centrifuged at 1,000 rpm for 20 min at 4°C and washed five times with PBS (pH =7.4). Then the collected RBCs were diluted with PBS 10 times.…”

Section: Hemolysis Testmentioning

confidence: 99%

“…Figure 5B shows the percentage of hemolysis at three concentrations (1, 10, and 20 µg/mL) after 2 and 24 h. It appears that there is no hemolytic activity of all tested concentrations for up to 24 h with a hemolysis percentage <10% as indicated in the literature. 35 All used concentrations were above the MIC of the developed nanoantibiotic with a negligible hemolytic activity associated with cellular biocompatibility that favors their use for in vivo applications.…”

mentioning

confidence: 97%

Single-walled carbon nanotubes-ciprofloxacin nanoantibiotic: strategy to improve ciprofloxacin antibacterial activity

Assali¹,

Zaid²,

Abdallah³

et al. 2017

IJN

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As infectious diseases continue to be one of the greatest health challenges worldwide, the demand toward alternative agents is continuously increasing. Recent advancement in nanotechnology has expanded our ability to design and construct nanomaterials to treat bacterial infections. Carbon nanotubes are one among these nanomaterials. Herein, we describe the covalent functionalization of the single-walled carbon nanotubes (SWCNTs) with multiple molecules of ciprofloxacin. The prepared nanoantibiotics were characterized using different techniques, including transmission electron microscopy, Raman spectroscopy, and thermogravimetric analysis. The characterization of the nanoantibiotics confirmed the successful covalent functionalization of the SWCNTs with 55% of functionalization as has been observed by thermogravimetric analysis. The release profile revealed that 90% of the loaded ciprofloxacin was released within 2.5 h at pH 7.4 showing a first-order release profile with R 2 >0.99. Interestingly, the results of the antibacterial activity indicated that the functionalized SWCNTs have significant increase in the antibacterial activity against the three strains of bacteria – by 16-fold for Staphylococcus aureus and Pseudomonas aeruginosa and by 8-fold for Escherichia coli – in comparison to the ciprofloxacin free drug. Moreover, the synthesized nanoantibiotic showed high hemocompatibility and cytocompatibility over a wide concentration range.

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“…The method used in the current study was suggested by Amin et al, modification of Yalkowsky method (Krzyzaniak et al, 1997;Amin & Dannenfelser, 2006) as guidance for the pharmaceutical chemists in in vitro hemolysis studies. Two identical sets of samples for two incubation times at 10 and 60 min were prepared.…”

Section: Hemolysis Testmentioning

confidence: 99%

Optimization of PEGylated nanoemulsions for improved pharmacokinetics of BCS class II compounds

et al. 2013

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The objective of the study was the optimization of nanoemulsion formulations to prevent their rapid systemic clearance after intravenous administration. An amphiphilic PEG derivative DSPE-PEG (1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy-poly(polyethylene glycol) with different chain lengths and concentration was used as a nanoemulsion droplet surface modifier. The danazol loading in all nanoemulsions was kept on the same level of $2 mg/mL. In the present investigation, PEGylated and non-PEGylated nanoemulsions were compared in vitro phagocytosis by incubating with lung macrophages and in vivo after intravenous administration in rats. Danazol-containing nanoemulsions (NE) modified with various PEG chain lengths (2000-10 000) and concentrations (3-12 mg/mL) were prepared and characterized. Nanoemulsion droplets were reproducibly obtained in the size range of 213-340 nm. The nonPEGylated NE had the surface charge of À25.4 mV. This absolute charge value decreased with increasing chain length and concentration. With increase in chain length and density the macrophage uptake decreased which could be due to decrease in surface charge and hydrophilicity of droplets. The greatest shielding of the NE droplets was reached with DSPE-PEG 5000 at the concentration of 6 mg/mL where the surface charge changed to À1.27 mV. Following intravenous administration a maximum danazol exposure (401 AE 68.2 h ng/mL) was observed with the lowest clearance rate (5.06 AE 0.95 L/h/kg) from 6 mg/mL DSPE-PEG 5000 nanoemulsion. PEG 5000 and PEG 10000 altered the pharmacokinetic of danazol by decreasing clearance and volume of distribution which is likely explained by the presence of hydrophilic shields around the droplets that prevent their rapid systemic clearance and tissue partitioning.

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In vitro hemolysis: Guidance for the pharmaceutical scientist

Cited by 283 publications

References 3 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

Single-walled carbon nanotubes-ciprofloxacin nanoantibiotic: strategy to improve ciprofloxacin antibacterial activity

Optimization of PEGylated nanoemulsions for improved pharmacokinetics of BCS class II compounds

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