The Experts below are selected from a list of 306 Experts worldwide ranked by ideXlab platform
Heike Bunjes - One of the best experts on this subject based on the ideXlab platform.
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Heat Treatment of Poloxamer-Stabilized Triglyceride Nanodispersions: Effects and Underlying Mechanism
2018Co-Authors: Katrin Göke, Elin Roese, Heike BunjesAbstract:Lipid nanoemulsions are being investigated for the parenteral administration of poorly soluble drugs. A narrow particle size distribution in these formulations is a prerequisite for meaningful research and safe administration to patients. Autoclaving a poloxamer-stabilized Trimyristin nanoemulsion resulted in moderate particle growth and a strong decrease in particle size distribution width (Göke, K.; Roese, E.; Arnold, A.; Kuntsche, J.; Bunjes, H. Mol. Pharmaceutics 2016, 13, 3187.). In this work, the critical parameters for such a change upon autoclaving poloxamer 188-stabilized lipid nanodispersions were investigated to elucidate the underlying mechanism. Nanodispersions of triglycerides with esterified fatty acid chain lengths from C8 to C18 were treated at different temperatures and for varying durations. The influence of a decrease in poloxamer 188’s cloud point was tested by adding potassium chloride to the dispersions prior to autoclaving. The influence of poloxamer 188 concentration and of the type of emulsifier was investigated. The change in particle size and particle size distribution width upon heat treatment was analyzed by dynamic or static light scattering or differential scanning calorimetry. A short esterified fatty acid chain length of the triglycerides, high temperatures, and the addition of potassium chloride were key factors for particle growth up to emulsion break up, whereas the cloud point of poloxamer 188 was irrelevant. Sodium dodecyl sulfate and sucrose laurate had negative effects on emulsion stability during autoclaving. It was concluded that the increase in particle size and the decrease in particle size distribution widths upon heat treatment resulted from heat-accelerated Ostwald ripening and not from a coalescence-based process
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control over particle size distribution by autoclaving poloxamer stabilized Trimyristin nanodispersions
Molecular Pharmaceutics, 2016Co-Authors: Katrin Goke, Elin Roese, Andreas Arnold, Judith Kuntsche, Heike BunjesAbstract:Lipid nanoparticles are under investigation as delivery systems for poorly water-soluble drugs. The particle size in these dispersions strongly influences important pharmaceutical properties like biodistribution and drug loading capacity; it should be below 500 nm for direct injection into the bloodstream. Consequently, small particles with a narrow particle size distribution are desired. Hitherto, there are, however, only limited possibilities for the preparation of monodisperse, pharmaceutically relevant dispersions. In this work, the effect of autoclaving at 121 °C on the particle size distribution of lipid nanoemulsions and -suspensions consisting of the pharmaceutically relevant components Trimyristin and poloxamer 188 was studied. Additionally, the amount of emulsifier needed to stabilize both untreated and autoclaved particles was assessed. In our study, four dispersions of mean particle sizes from 45 to 150 nm were prepared by high-pressure melt homogenization. The particle size distribution before and after autoclaving was characterized using static and dynamic light scattering, differential scanning calorimetry, and transmission electron microscopy. Asymmetrical flow field-flow fractionation was used for particle size distribution analyses and for the determination of free poloxamer 188. Upon autoclaving, the mean particle size increased to up to 200 nm, but not proportionally to the initial size. At the same time, the particle size distribution width decreased remarkably. Heat treatment thus seems to be a promising approach to achieve the desired narrow particle size distribution of such dispersions. Related to the lipid content, suspension particles needed more emulsifier for stabilization than emulsion droplets, and smaller particles more than larger ones.
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Control over Particle Size Distribution by Autoclaving Poloxamer-Stabilized Trimyristin Nanodispersions
2016Co-Authors: Katrin Göke, Andreas Arnold, Elin Roese, Judith Kuntsche, Heike BunjesAbstract:Lipid nanoparticles are under investigation as delivery systems for poorly water-soluble drugs. The particle size in these dispersions strongly influences important pharmaceutical properties like biodistribution and drug loading capacity; it should be below 500 nm for direct injection into the bloodstream. Consequently, small particles with a narrow particle size distribution are desired. Hitherto, there are, however, only limited possibilities for the preparation of monodisperse, pharmaceutically relevant dispersions. In this work, the effect of autoclaving at 121 °C on the particle size distribution of lipid nanoemulsions and -suspensions consisting of the pharmaceutically relevant components Trimyristin and poloxamer 188 was studied. Additionally, the amount of emulsifier needed to stabilize both untreated and autoclaved particles was assessed. In our study, four dispersions of mean particle sizes from 45 to 150 nm were prepared by high-pressure melt homogenization. The particle size distribution before and after autoclaving was characterized using static and dynamic light scattering, differential scanning calorimetry, and transmission electron microscopy. Asymmetrical flow field–flow fractionation was used for particle size distribution analyses and for the determination of free poloxamer 188. Upon autoclaving, the mean particle size increased to up to 200 nm, but not proportionally to the initial size. At the same time, the particle size distribution width decreased remarkably. Heat treatment thus seems to be a promising approach to achieve the desired narrow particle size distribution of such dispersions. Related to the lipid content, suspension particles needed more emulsifier for stabilization than emulsion droplets, and smaller particles more than larger ones
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development of a new approach to investigating the drug transfer from colloidal carrier systems applying lipid nanosuspension containing alginate microbeads as acceptor
International Journal of Pharmaceutics, 2015Co-Authors: Birthe Strasdat, Heike BunjesAbstract:Abstract As a new approach to analyzing the release behavior of lipophilic drugs from colloidal carriers, solid Trimyristin nanoparticles were incorporated into differently sized (34–1363 μm) calcium alginate hydrogel microbeads to serve as acceptor in release studies. The microbeads were prepared by electrostatic droplet generation or by a spraying method. Trimyristin nanoemulsion samples loaded with the fluorescent drug model Nile red were mixed with the nanoparticle-containing microbeads to perform transfer studies. As a result of a rather large diffusion barrier a slow transfer (24–57 min) was observed using large acceptor beads (∼330–1360 μm). In contrast, Nile red transferred quickly (∼1.4 min) into smaller microbeads (
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evaluation of shirasu porous glass spg membrane emulsification for the preparation of colloidal lipid drug carrier dispersions
European Journal of Pharmaceutics and Biopharmaceutics, 2014Co-Authors: Sonja Joseph, Heike BunjesAbstract:Aqueous colloidal drug carrier dispersions based on nonpolar lipids are usually prepared by high energy dispersion techniques, like high-pressure homogenization. Homogenization generates high shear forces and may thus not be suitable for the processing of sensitive pharmaceutical ingredients, e.g., proteins. This study investigated the general possibility to prepare lipid nanoparticle dispersions by direct and premix Shirasu Porous Glass (SPG) membrane emulsification as alternative low energy and low shear method. The influence of different emulsifiers (polysorbate 20, sorbitan oleate, poloxamer 188, sodium dodecyl sulfate, sucrose laurate), the type of lipid phase (medium chain triglycerides, soybean oil, Trimyristin, glyceryl behenate, lauroyl macrogolglycerides), the pore size of the SPG membrane (0.1, 0.2, 0.3, 0.5, 1.1μm) and the emulsifying pressure on the particle size of the resulting dispersions was investigated. The particle size was primarily controlled by the pore size of the membrane and the emulsifying pressure. Very narrow particle size distributions with membrane pore size/mean particle size ratios of 1:0.4-1:8.2 and 1:0.4-1:2.1 were observed for the direct and the premix membrane emulsification method, respectively. Due to the comparatively lower process pressures of at maximum 10bar SPG membrane emulsification is an interesting alternative method to high-pressure homogenization.
Jeanpierre Benoit - One of the best experts on this subject based on the ideXlab platform.
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In vivo evaluation of lipid nanocapsules as a promising colloidal carrier for paclitaxel.
International Journal of Pharmaceutics, 2007Co-Authors: Franck Lacoeuille, François Hindré, Fréderic Moal, Jérome Roux, Catherine Passirani, Olivier Couturier, Paul Calès, Jean-jacques Le Jeune, Alf Lamprecht, Jeanpierre BenoitAbstract:Paclitaxel-loaded lipid nanocapsules (PX-LNC) exhibit interesting in vitro characteristics with improved antitumoral activity compared with free PX formulation. Biodistribution studies were realized with the use of (14)C-Trimyristin ((14)C-TM) or (14)C-phosphatidylcholine ((14)C-PC) whereas antitumoral activity of PX-LNC formulations was based on the animal survival in a chemically induced hepatocellular carcinoma (HCC) model in Wistar rats. Blood concentration-time profiles for both labeled (14)C-TM-LNC and (14)C-PC-LNC were similar; the t(1/2) and MRT values (over 2h and close to 3h, respectively, for both formulations) indicated the long circulating properties of the LNC carrier with a slow distribution and elimination phase. Survival curves of paclitaxel treated groups showed a statistical significant difference compared to the control survival curve (P=0.0036 and 0.0408). Animals treated with 4x 70 mg/m(2) of PX-LNC showed the most significant increase in mean survival times compared to the controls (IST(mean) 72%) and cases of long-term survivors were preferentially observed in the PX-LNC treated group (37.5%; 3/8). These results demonstrate the great interest to use LNC as drug delivery system for paclitaxel, permitting with an equivalent therapeutic efficiency to avoid the use of excipients such as polyoxyethylated castor oil for its formulation.
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a supercritical fluid based coating technology 3 preparation and characterization of bovine serum albumin particles coated with lipids
Journal of Microencapsulation, 2003Co-Authors: Ribeiro Dos I Santos, Joel Richard, C Thies, Brigitte Pech, Jeanpierre BenoitAbstract:Solvent-free microparticles, loaded with bovine serum albumin as a model protein, were produced using a novel supercritical (SC) fluid-based coating technology. Coating material consists either of Trimyristin (Dynasan® 114) or of Gelucire® 50-02. Microparticles obtained were characterized as regards their morphology, protein content and in vitro release profile. A discontinuous coating made of micro-needles of Trimyristin led to an initial burst release of ∼ 70% in 30min. However, a prolonged release of the BSA could be achieved in a phosphate buffer solution at 37 °C over a 24 h period from particles coated with Gelucire® 50-02. Furthermore, it was shown that BSA does not undergo any degradation after SC CO2 treatment under the conditions used in the coating process.
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a supercritical fluid based coating technology 1 process considerations
Journal of Microencapsulation, 2003Co-Authors: C Thies, Ribeiro Dos I Santos, Joel Richard, V Vandevelde, Herve Rolland, Jeanpierre BenoitAbstract:A novel solvent-free particle coating process, based on the solvent properties of supercritical fluids (SCF) is described. It consists of dissolving one or more coating materials in supercritical CO2 and then adjusting T/P conditions in the autoclave so that the coating material becomes insoluble in the CO2. This insolubilization step causes a coating to deposit on the surface of suspended particles. This process has been applied to bovine serum albumin and sugar granules. Coating was effective, but different morphologies were obtained depending on the coating material used. A discontinuous coating has been made using Trimyristin, since this material precipitates as micro-needles. Conversely, a smooth, regular coating has been obtained with a commercially available mixture of glycerides and glyceride esters of PEG (Gelucire® 50/02 acting like a film-forming agent.
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a supercritical fluid based coating technology 2 solubility considerations
Journal of Microencapsulation, 2003Co-Authors: Ribeiro Dos I Santos, Joel Richard, C Thies, V Vandevelde, Le D Meurlay, V Gajan, Jeanpierre BenoitAbstract:Solubility measurements of candidate coating materials have been performed in supercritical (SC) CO2 so as to select appropriate coating materials for implementation of a solvent-free coating process previously described. Solubility of lipidic compounds such as waxes (paraffin, beeswax, Carnauba wax), pure triglycerides (tricaprin, Trimyristin, tripalmitin, tristearin) and mixture of glycerides and fatty acid esters (Gelucire®) in SC CO2 were evaluated in a static mode under different temperature and pressure conditions, ranging from 13–52°C and from 50–220 bar, whether the CO2 was in its liquid or SC state. It was shown that the compounds which are mixtures of various components give rise to a selective extraction of the lower melting point components, as evidenced from thermal analysis of soluble and insoluble fractions of the coating materials.
Vobalaboina Venkateswarlu - One of the best experts on this subject based on the ideXlab platform.
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development of sln and nlc enriched hydrogels for transdermal delivery of nitrendipine in vitro and in vivo characteristics
Drug Development and Industrial Pharmacy, 2009Co-Authors: Kesavan Bhaskar, Vobalaboina Venkateswarlu, Chinnala Krishna Mohan, Meka Lingam, Somagoni Jagan Mohan, J Anbu, V RavichandranAbstract:The purpose of this research was to investigate novel particulate carrier systems such as solid lipid nanoparticles (SLN) and nanostructured lipid carrier (NLC) for transdermal delivery of nitrendipine (NDP). For this investigation, four different gel-forming agents were selected for hydrogel preparation. Aqueous dispersions of lipid nanoparticles made from Trimyristin (TM) were prepared by hot homogenization technique followed by sonication and then incorporated into the freshly prepared hydrogels. The particle size was analyzed by photon correlation spectroscopy (PCS) using Malvern zetasizer, which shows that for all the tested formulations, more than 50% of the particles were below 250 nm after 90 days of storage at room temperature. DSC analysis was performed to characterize the state of drug and lipid modification. Shape and surface morphology were determined by scanning electron microscope (SEM) and transmission electron microscope (TEM), which revealed fairly spherical shape of the formulations. Th...
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pharmacokinetics tissue distribution and bioavailability of nitrendipine solid lipid nanoparticles after intravenous and intraduodenal administration
Journal of Drug Targeting, 2006Co-Authors: Kopparam Manjunath, Vobalaboina VenkateswarluAbstract:Purpose: The aim of this research was to study whether the bioavailability of nitrendipine (NDP) could be improved by administering nitrendipine solid lipid nanoparticles (SLN) duodenally to rats.Methods: Nitrendipine was incorporated into SLN prepared by hot homogenization followed by ultrasonication method. SLN were produced using various triglycerides (Trimyristin, tripalmitin and tristearin), soy phosphatidylcholine 95%, poloxamer 188 and charge modifiers (dicetyl phosphate, DCP and stearylamine, SA). Particle size and charge measurements were made with a Malvern Zetasizer. Pharmacokinetics of nitrendipine SLNs (NDP-SLNs) after intravenous (i.v.) and intraduodenal (i.d.) administration to conscious male Wistar rats were studied. Tissue distribution studies of NDP-SLNs were carried out in Swiss albino mice after i.v. administration and compared to nitrendipine suspension (NDP-Susp).Results: Average size and zeta potential of SLNs of different lipids, with and without charge modifiers ranged from 101.9 ...
Ulla M Elofsson - One of the best experts on this subject based on the ideXlab platform.
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tracking single lipase molecules on a Trimyristin substrate surface using quantum dots
Langmuir, 2007Co-Authors: Andreas W Sonesson, Thomas H Callisen, Ulla M Elofsson, Hjalmar BrismarAbstract:The mobility of single lipase molecules has been analyzed using single molecule tracking on a Trimyristin substrate surface. This was achieved by conjugating lipases to quantum dots and imaging on spin-coated Trimyristin surfaces by means of confocal laser scanning microscopy. Image series of single lipase molecules were collected, and the diffusion coefficient was quantified by analyzing the mean square displacement of the calculated trajectories. During no-flow conditions, the lipase diffusion coefficient was (8.0+/-5.0)x10(-10) cm2/s. The trajectories had a "bead on a string" appearance, with the lipase molecule restricted in certain regions of the surface and then migrating to another region where the restricted diffusion continued. This gave rise to clusters in the trajectories. When a flow was applied to the system, the total distance and average step length between the clusters increased, but the restricted diffusion in the cluster regions was unaffected. This can be explained by the lipase operating in two different modes on the surface. In the cluster regions, the lipase is likely oriented with the active site toward the surface and hydrolyzes the substrate. Between these regions, a diffusion process is proposed where the lipase is in contact with the surface but affected by the external flow.
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mobility of thermomyces lanuginosus lipase on a Trimyristin substrate surface
Langmuir, 2007Co-Authors: Andreas W Sonesson, Hjalmar Brismar, Thomas H Callisen, Ulla M ElofssonAbstract:We have studied the mobility of active and inactive Thermomyces lanuginosus lipase (TLL) on a spin-coated Trimyristin substrate surface using fluorescence recovery after photobleaching (FRAP) in a confocal microscopy setup. By photobleaching a circular spot of fluorescently labeled TLL adsorbed on a smooth Trimyristin surface, both the diffusion coefficient D and the mobile fraction f could be quantified. FRAP was performed on surfaces with different surface density of lipase and as a function of time after adsorption. The data showed that the mobility of TLL was significantly higher on the Trimyristin substrate surfaces compared to our previous studies on hydrophobic model surfaces. For both lipase variants, the diffusion decreased to similar rates at high relative surface density of lipase, suggesting that crowding effects are dominant with higher adsorbed amount of lipase. However, the diffusion coefficient at extrapolated infinite surface dilution, D0, was higher for the active TLL compared to the inactive (D0 = 17.9 x 10(-11) cm2/s vs D0 = 4.1 x 10(-11) cm2/s, data for the first time interval after adsorption). Moreover, the diffusion decreased with time after adsorption, most evident for the active TLL. We explain the results by product inhibition, i.e., that the accumulation of negatively charged fatty acid products decreased the diffusion rate of active lipases with time. This was supported by sequential adsorption experiments, where the adsorbed amount under flow conditions was studied as a function of time after adsorption. A second injection of lipase led to a significantly lower increase in adsorbed amount when the Trimyristin surface was pretreated with active TLL compared to pretreatment of inactive TLL.
Hjalmar Brismar - One of the best experts on this subject based on the ideXlab platform.
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tracking single lipase molecules on a Trimyristin substrate surface using quantum dots
Langmuir, 2007Co-Authors: Andreas W Sonesson, Thomas H Callisen, Ulla M Elofsson, Hjalmar BrismarAbstract:The mobility of single lipase molecules has been analyzed using single molecule tracking on a Trimyristin substrate surface. This was achieved by conjugating lipases to quantum dots and imaging on spin-coated Trimyristin surfaces by means of confocal laser scanning microscopy. Image series of single lipase molecules were collected, and the diffusion coefficient was quantified by analyzing the mean square displacement of the calculated trajectories. During no-flow conditions, the lipase diffusion coefficient was (8.0+/-5.0)x10(-10) cm2/s. The trajectories had a "bead on a string" appearance, with the lipase molecule restricted in certain regions of the surface and then migrating to another region where the restricted diffusion continued. This gave rise to clusters in the trajectories. When a flow was applied to the system, the total distance and average step length between the clusters increased, but the restricted diffusion in the cluster regions was unaffected. This can be explained by the lipase operating in two different modes on the surface. In the cluster regions, the lipase is likely oriented with the active site toward the surface and hydrolyzes the substrate. Between these regions, a diffusion process is proposed where the lipase is in contact with the surface but affected by the external flow.
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mobility of thermomyces lanuginosus lipase on a Trimyristin substrate surface
Langmuir, 2007Co-Authors: Andreas W Sonesson, Hjalmar Brismar, Thomas H Callisen, Ulla M ElofssonAbstract:We have studied the mobility of active and inactive Thermomyces lanuginosus lipase (TLL) on a spin-coated Trimyristin substrate surface using fluorescence recovery after photobleaching (FRAP) in a confocal microscopy setup. By photobleaching a circular spot of fluorescently labeled TLL adsorbed on a smooth Trimyristin surface, both the diffusion coefficient D and the mobile fraction f could be quantified. FRAP was performed on surfaces with different surface density of lipase and as a function of time after adsorption. The data showed that the mobility of TLL was significantly higher on the Trimyristin substrate surfaces compared to our previous studies on hydrophobic model surfaces. For both lipase variants, the diffusion decreased to similar rates at high relative surface density of lipase, suggesting that crowding effects are dominant with higher adsorbed amount of lipase. However, the diffusion coefficient at extrapolated infinite surface dilution, D0, was higher for the active TLL compared to the inactive (D0 = 17.9 x 10(-11) cm2/s vs D0 = 4.1 x 10(-11) cm2/s, data for the first time interval after adsorption). Moreover, the diffusion decreased with time after adsorption, most evident for the active TLL. We explain the results by product inhibition, i.e., that the accumulation of negatively charged fatty acid products decreased the diffusion rate of active lipases with time. This was supported by sequential adsorption experiments, where the adsorbed amount under flow conditions was studied as a function of time after adsorption. A second injection of lipase led to a significantly lower increase in adsorbed amount when the Trimyristin surface was pretreated with active TLL compared to pretreatment of inactive TLL.
