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T Rades

Publications and source records attributed to T Rades.

At least 19 recordsLinked to original sources
PubMed2006

Cage-like complexes formed by DOTAP, Quil-A and cholesterol.

In this note we describe the substitution of the phospholipid component in classical ISCOMs (immune-stimulating complexes) with the cationic lipid dioleoyl-trimethyl-ammonium-propane (DOTAP). The self-assembled colloidal structures formed by DOTAP, Quil-A and cholesterol were characterised using transmission electron microscopy and laser Doppler velocimetry. Samples were prepared using the lipid-film hydration and dialysis techniques. Cage-like structures containing DOTAP were obtained in high numbers using dialysis, but not lipid-film hydration on day 4 post-preparation. The formation of cage-like structures was however only observed at compositions with low weight proportions of DOTAP (less than 25%) resulting in neutral to negative zeta-potentials of the colloidal particles. Compositions with high weight proportions of DOTAP displayed phase separation phenomena. Thus, whilst DOTAP can be incorporated with Quil-A and cholesterol to form cage-like particles, it appears to be unsuitable to prepare cationic equivalents of ISCOMs.

Adjuvants, Immunologic↗
PubMed2006

Characterisation of bicontinuous cubic liquid crystalline systems of phytantriol and water using cryo field emission scanning electron microscopy (cryo FESEM).

Cubosomes are a novel lipid particulate delivery system currently being investigated for drug delivery purposes. The present study investigates bicontinuous cubic liquid crystalline systems (bulk phase and cubosomes) formed by phytantriol and water using cryo field emission scanning electron microscopy (cryo FESEM). Previously cubosomes have been characterized by cryo transmission electron microscopy (cryo TEM) with small angle X-ray diffraction (SAXS) confirming the bicontinuous liquid crystalline type. Bulk cubic phase and cubosomes were prepared from phytantriol and Pluronic F127 and analysed using cryo FESEM and SAXS. The micrographs showed the cubic phase had a tortuous, bicontinuous nature with a non-intersecting network of water channels. The cubosomes also show the same underlying tortuous structure entirely consistent with that of the bulk cubic phase and closely resemble the mathematical description of cubosomes described using nodal surface representation. The structure of both systems was confirmed using SAXS as a bicontinuous cubic liquid crystalline phase with Pn3m geometry. Cryo FESEM provides valuable insights into the morphological features of bicontinuous cubic liquid crystalline systems. The unique details shown provide strength to support the nodal surface representation of bicontinuous cubic liquid crystalline systems. Cryo FESEM provides a new technique to complement cryo TEM and SAXS for investigating their structure and function.

Cryoelectron Microscopy↗
PubMed2006

Effect of milling conditions on the solid-state conversion of ranitidine hydrochloride form 1.

Powder samples of ranitidine hydrochloride forms 1 and 2 were milled using a vibrational ball mill (Retsch MM301) for periods up to 240min at 4, 12 and 35 degrees C. X-ray powder diffraction (XRPD), diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS), solid-state nuclear magnetic resonance (NMR) and differential scanning calorimetry (DSC) were used to monitor solid-state properties of the milled samples. Milling of form 1 at 4 degrees C led to a powder temperature of 36 degrees C in the milling chamber and produced only amorphous drug; at 12 degrees C (powder temperature 45 degrees C) and at 35 degrees C (powder temperature 62 degrees C) progressive transformation of form 1 via amorphous drug to form 2 occurred. DSC of the milled samples showed a glass transition at 13-30 degrees C and a crystallization exotherm (T(c)) between 30 and 65 degrees C if the sample contained amorphous drug. The behaviour of the solid was speculated to be influenced by the relationship between powder temperature and T(c); at powder temperatures below T(c), amorphous drug is formed but no crystallization of form 2 occurs; at temperatures close to T(c), amorphous content initially increases with transformation to form 2 on continued milling. At temperatures much higher than T(c), at intermediate stages, less amorphous drug but both form 1 and form 2 are recovered, but continued milling gives only form 2. Form 2 did not transform to form 1 under any conditions used in this study.

Calorimetry, Differential Scanning↗
PubMed2006

Visualizing the conversion of carbamazepine in aqueous suspension with and without the presence of excipients: a single crystal study using SEM and Raman microscopy.

Visual observations of the hydration process of single carbamazepine (CBZ) crystals in water and in various excipient solutions [(1% w/v) - hydroxypropyl cellulose (HPC), poly(vinyl pyrrolidone) (PVP), sodium carboxymethylcellulose (CMC) at pH 7.5 and 3.0, and polyethylene glycol (PEG)] using scanning electron microscopy (SEM) are reported in this paper. Raman microscopy was used to confirm the chemical structures of the unconverted CBZ and the CBZ dihydrate (DH) needles. It was found that defect structures were a more important driving force than the nature of crystal faces for the initiation of the hydration, but face differences became obvious after 6 h immersion. The biggest crystal face grown from methanol, (100), was the slowest one to be covered with DH needles. A comparison of the molecular arrangements along the three crystal faces [(100), (010) and (001)] was carried out using crystal structure visualization software, and fewer polar groups exposed on the (100) face than on the (001) and (010) faces were found, explaining the comparatively weak interaction of the (100) face with water during hydration. Furthermore, investigation of the influence of excipients on the hydration of CBZ showed that both HPC and PVP strongly inhibited conversion, and no conversion of CBZ to DH was found after 18 h immersion in water. PEG and CMC (pH 7.5) were less potent inhibitors than HPC and PVP, and DH needles were observed on all the faces except the (100) face after 18 h immersion. No conversion was detected for the crystal immersed in CMC solution at pH 3.0. This is likely to be caused by the decreased polarity of CMC in water at pH 3.0 (pKa,cmc = 4.3), and thus a higher surface adsorption of CMC to the CBZ crystals in dispersion. The influence of excipients on the conversion of CBZ observed in this study agreed well with our previous quantitative studies using Raman spectroscopy. In this study, visual observation using electron microscopy has been demonstrated to be a unique and powerful tool to improve our understanding of polymorphic conversions of CBZ in aqueous suspension.

Carbamazepine↗
PubMed2006

Analysis of lecithin-cholesterol mixtures using Raman spectroscopy.

FT-Raman spectroscopy has been used to investigate interactions between lecithin and cholesterol. Raman spectra of lecithin show multiple peaks which can be classified into three regions: hydrophobic chain, interfacial, and headgroup regions. Binary lipid mixtures (1:1, w/w, lecithin:cholesterol) were prepared by physical mixing, granulation, coprecipitation, hydration and heating (65 degrees C), and heating (120 degrees C). Regardless of the preparation method, no changes in the spectra were observed in the hydrophobic region. A shift in the wavenumber of the choline methyl asymmetric stretching mode was observed when the samples were prepared by coprecipitation, hydration and heating (65 degrees C), and heating (120 degrees C). This may indicate a modification of phospholipids in the headgroup region in these samples. The difference in degrees of frequency shift (physical mixing approximately granulation<coprecipitation approximately hydration and heating (65 degrees C)<heating (120 degrees C)) suggests that different levels of hydrogen bonding may have occurred in mixtures prepared with these methods. Multivariate analysis utilizing partial least squares regression based on selected wavenumber ranges was applied for the quantitative analysis of the amount of lecithin in lipid mixtures. Calibration models from physical mixing and heating (120 degrees C) exhibited lower R2 and root mean square error of cross validation (RMSECV) values compared to the other models suggesting lower sample homogeneity for these preparation methods. Low values of the mean absolute residues and mean Mahalanobis distances imply that the calibration model generated from physical mixing samples may be appropriate for quantitative analysis of lecithin in lipid mixtures prepared by any of the other techniques.

Chemistry, Pharmaceutical↗
PubMed2006

W/O microemulsions for ocular delivery: evaluation of ocular irritation and precorneal retention.

Water-in-oil microemulsions (w/o ME) capable of undergoing a phase-transition to lamellar liquid crystals (LC) or bicontinuous ME upon aqueous dilution were formulated using Crodamol EO, Crill 1 and Crillet 4, an alkanol or alkanediol as cosurfactant and water. The hypothesis that phase-transition of ME to LC may be induced by tears and serve to prolong precorneal retention was tested. The ocular irritation potential of components and formulations was assessed using a modified hen's egg chorioallantoic membrane test (HET-CAM) and the preocular retention of selected formulations was investigated in rabbit eye using gamma scintigraphy. Results showed that Crill 1, Crillet 4 and Crodamol EO were non-irritant. However, all other cosurfactants investigated were irritant and their irritation was dependent on their carbon chain length. A w/o ME formulated without cosurfactant showed a protective effect when a strong irritant (0.1 M NaOH) was used as the aqueous phase. Precorneal clearance studies revealed that the retention of colloidal and coarse dispersed systems was significantly greater than an aqueous solution with no significant difference between ME systems (containing 5% and 10% water) as well as o/w emulsion containing 85% water. Conversely, a LC system formulated without cosurfactant displayed a significantly greater retention compared to other formulations.

Animals↗
PubMed2006

Understanding the influence of polymorphism on phonon spectra: lattice dynamics calculations and terahertz spectroscopy of carbamazepine.

Rigid molecule atomistic lattice dynamics calculations have been performed to predict the phonon spectra of the four polymorphs of carbamazepine, and these calculations predict that there should be differences in the spectra of all four forms. Terahertz spectra have been measured for forms I and III, and there are clearly different features between polymorphs' spectra, that are accentuated at low temperature. While carbamazepine adopts the same hydrogen bonded dimers in all of its known polymorphs, the calculations show that differences in packing arrangements of the dimers lead to changes in the frequency ranges for each type of hydrogen bond vibration, giving a physical explanation to the observed differences between the spectra. Although the agreement between calculated and observed spectra does not allow a definitive characterization of the spectra, it is possible to make tentative assignments of many of the observed features in the terahertz region for the simpler form III; we can only make some tentative assignments of specific modes in the more complex spectrum of form I. While harmonic rigid molecule lattice dynamics shows promise for understanding the differences in spectra between polymorphs of organic molecules, discrepancies between observed and calculated spectra suggest areas of improvement in the computational methods for more accurate modeling of the dynamics in molecular organic crystals.

Carbamazepine↗
PubMed2006

On the dilution behaviour of immuno-stimulating complexes (ISCOMs).

Immunostimulating complexes (ISCOMs) are used as potent vaccine delivery systems. However, the mechanisms by which ISCOMs work are mostly unknown. The immunological potency of ISCOMs has often been associated with their characteristic cage-like structure. Since ISCOMs can be regarded as composite mixed micelles that contain Quillaja saponin as the surfactant, we postulated a micelle to vesicle transition of the particles upon dilution with aqueous solutions. The dilution behaviour of ISCOMs is not only an important preparative aspect, but may also be of high relevance for both cell culture and in vivo applications in which dilutions occur. Crude and purified preparations of ISCOM matrices were prepared by dialysis. Methods used to analyse the micelle to vesicle transitions were transmission electron microscopy and dynamic light scattering. Significant morphological changes occurred upon dilution with TRIS buffered saline and non-buffered saline, and a step-wise transition from the typical cage-like structure via both less well defined ISCOM-like structures and helical micelles to small lipidic particles was observed. Aggregation of the resulting small lipidic particles was noted. The results obtained by dynamic light scattering complemented these findings. With increasing dilution factors, increase in particle size and polydispersity was observed. Zeta-potentials showed a trend towards less negative values upon dilution, indicating that saponins were not retained within the lipid matrix. The results indicated that at least partial separation of Quillaja saponins from the remaining colloidal species occurred upon dilution with aqueous solutions. The release of saponins upon dilution may be an important aspect of how ISCOMs work.

Adjuvants, Immunologic↗
PubMed2006

Characterisation of microemulsions containing orange oil with water and propylene glycol as hydrophilic components.

The current study aims to investigate the effect of incorporation of orange oil, mainly consisting of the cyclic mono-terpene linolene, a known skin penetration enhancer, as oil component on microemulsion formation both in water and propylene glycol containing systems. Phase diagrams of pseudoternary mixtures containing orange oil, ethyloleate or a 1:1 mixture (w/w) of orange oil and ethyloleate as oil components, a 6:4 (w/w) mixture of polyoxyethylene 20 sorbitan monooleate and sorbitan monolaurate as surfactant components and water or propylene glycol as hydrophilic components were investigated. Smaller microemulsion regions were observed when orange oil was used as a substitute for ethyloleate in both water and propylene glycol containing systems. Polarising light microscopy, viscosity measurements, electrical conductivity measurements and cryo-field emission scanning electron microscopy were used to identify structural features of the microemulsions. Solution-type, w/o droplet-type microemulsions and microemulsion areas containing liquid crystals were found in varying areas in the phase diagrams of water containing systems. Liquid crystals formation occurs when the water concentration reaches 20%-22.5% (w/w). Only solution-type microemulsions were observed in propylene glycol containing systems. The dimension of solution-type microemulsion areas in the phase diagrams is likely to depend on the miscibility of components and larger microemulsion areas were found when ethyloleate was used instead of orange oil and propylene glycol was used instead of water. W/o droplet-type microemulsions of systems containing orange oil and ethyloleate as oil components appear in different areas of the phase diagrams. Incorporation of orange oil as a penetration enhancer into a topical microemulsion affects its physical characteristics. This in turn may lead to instability of the microemulsion and/or can influence the release patterns of drugs from these microemulsions when applied as topical formulations.

Administration, Topical↗
PubMed2006

Characterisation of microstructures formed in isopropyl palmitate/water/Aerosol OT:1-butanol (2:1) system.

The aim of this work was to determine the type and microstructure of microemulsion samples formed in IPP/water/AerosolOT:1-butanol (2:1) systems as a case study for the investigation of microemulsions. The concentration of the surfactant/cosurfactant mixture was kept constant while the ratio of water to oil was varied. Several techniques were used to investigate the types and phase transitions of the microemulsion formulations. The experimental methods used included visual observation cross-polarized light microscopy (PLM) appearance, conductivity, viscosity, cryo-field emission scanning electron microscopy (cryo-FESEM), differential scanning calorimetry (DSC), nuclear magnetic resonance (NMR), and fluorescence resonance energy transfer (FRET). Taken together, the results of the various techniques imply that the systems investigated are undergoing two transitions as a function of water concentration. Between 10-15%w/w of water, the systems change from headgroup hydrated surfactant solutions in oil (or possibly very small reversed micellar systems) to w/o microemulsions. These systems then change to o/w microemulsions between 25-30%w/w of water. The transitions however, appear to be gradual, as for example the DSC data indicates a transition between 15-20%w/w of water. Furthermore, for some methods the changes observed were very weak, and only with supportive data of other techniques can the phase behaviour of the microemulsion systems be interpreted with confidence. Interestingly, no indication of the presence of a bicontinuous intermediate microstructure was found. Liquid crystal formation was detected in samples containing 55%w/w of water.

1-Butanol↗
PubMed2005

Characterizing the conversion kinetics of carbamazepine polymorphs to the dihydrate in aqueous suspension using Raman spectroscopy.

In an aqueous environment, polymorphic forms I-III of carbamazepine all convert to the dihydrate. This study investigated the conversion of each polymorphic form individually and of a mixture of forms III and I to the dihydrate. Two batches of form I with different crystal morphology were used. Samples were dispersed independently in water at 23+/-1 degrees C and recovered at various timepoints varying from 10 to 210 min. Scanning electron microscopy, X-ray powder diffraction and Raman spectroscopy were used to characterize the initial polymorphic forms and the recovered samples after 210 min. Raman spectroscopy combined with partial least squares analysis was used to generate quantitative models of binary and ternary mixtures of the different polymorphic forms with the dihydrate. On the basis of these models the conversion kinetics of the polymorphic forms I-III were characterized. First-order kinetics with an unconverted portion were used to model the data (R2> or =0.95). The unconverted portions ranged from 16 to 51% after dispersion for 210 min. The conversion kinetics were similar between polymorphic forms with comparable crystal morphology, but differed significantly between batches of the same polymorph (form I) with different crystal morphology. Furthermore, the conversion of forms III and I in the aqueous suspension was not influenced by the presence of the other polymorph when dispersed together.

Anticonvulsants↗
PubMed2005

Using different structure types of microemulsions for the preparation of poly(alkylcyanoacrylate) nanoparticles by interfacial polymerization.

A phase diagram of the pseudoternary system ethyloleate, polyoxyethylene 20 sorbitan mono-oleate/sorbitan monolaurate and water with butanol as a cosurfactant was prepared. Areas containing optically isotropic, low viscosity one-phase systems were identified and systems therein designated as w/o droplet-, bicontinuous- or solution-type microemulsions using conductivity, viscosity, cryo-field emission scanning electron microscopy and self-diffusion NMR. Nanoparticles were prepared by interfacial polymerization of selected w/o droplet, bicontinuous- or solution-type microemulsions with ethyl-2-cyanoacrylate. Morphology of the particles and entrapment of the water-soluble model protein ovalbumin were investigated. Addition of monomer to the different types of microemulsions (w/o droplet, bicontinuous, solution) led to the formation of nanoparticles, which were similar in size ( approximately 250 nm), polydispersity index ( approximately 0.13), zeta-potential ( approximately -17 mV) and morphology. The entrapment of the protein within these particles was up to 95%, depending on the amount of monomer used for polymerization and the type of microemulsion used as a polymerization template. The formation of particles with similar characteristics from templates having different microstructure is surprising, particularly considering that polymerization is expected to occur at the water-oil interface by base-catalysed polymerization. Dynamics within the template (stirring, viscosity) or indeed interfacial phenomena relating to the solid-liquid interface appear to be more important for the determination of nanoparticle morphology and characteristics than the microstructure of the template system.

1-Butanol↗
PubMed2004

A comparison of pseudo-ternary diagrams of aqueous mixtures of Quil A, cholesterol and phospholipid prepared by lipid-film hydration and dialysis.

Pseudo-ternary diagrams for Quil A, phospholipid (phosphatidylcholine (PC) or phosphatidylethanolamine (PE)) and cholesterol were established in order to identify combinations that result in the formation of immune-stimulating complex (ISCOM) matrices and other colloidal structures produced by these three components in aqueous systems following lipid-film hydration or dialysis (methods that can be used to produce ISCOMs). In addition, the effect of equilibration time (1 month at 4 degrees C) on the structures formed by the various combinations of the three components was investigated. Depending on the ratio of Quil A, cholesterol and phospholipid, different colloidal particles, including ISCOM matrices, liposomes and ring-like micelles, were found irrespective of the preparation method used. In contrast, worm-like micelles were only observed in systems prepared by lipid-film hydration. For samples prepared by dialysis, ISCOM matrices were predominantly found near the Quil A apex of the pseudo-ternary diagram (> 50% Quil A). On the other hand, for samples prepared by lipid-film hydration, ISCOM matrices were predominantly found near the phospholipid apex of the pseudo-ternary diagram (> 50% phospholipid). The regions in the pseudo-ternary diagrams in which ISCOM matrices were observed increased following an extended equilibration time, particularly for samples prepared by lipid-film hydration. Differences were also observed between pseudoternary diagrams prepared using either PE or PC as phospholipids.

Adjuvants, Immunologic↗
PubMed2004

Uptake of antigen encapsulated in polyethylcyanoacrylate nanoparticles by D1-dendritic cells.

Polyethylcyanoacrylate (PECA) nanoparticles were prepared by interfacial polymerization of a water-in-oil microemulsion. Nanoparticles were isolated from the polymerization template by sequential ethanol washing and centrifugation. A nanocapsule preparation yielding the original particle size and distribution following redispersion in an aqueous solution was achieved by freeze-drying the isolated nanoparticles in a solution of 5% w/v sugar. The cytotoxicity and uptake of nanocapsules by dendritic cells was investigated using a murine-derived cell line (D1). PECA nanoparticles were found to adversely effect cell viability at concentrations greater than 10 microg/ml of polymer in the culture medium. In comparison to antigen in solution, cell uptake of antigen encapsulated within nanoparticles was significantly higher at both 4 and 37 degrees C. Following a 24 h incubation period, the percentage of cells taking-up antigen was also increased when antigen was encapsulated in nanoparticles as compared to antigen in solution. The uptake of nanoparticles and the effect of antigen formulation on morphological cell changes indicative of cell maturation were also investigated by scanning electron microscopy (SEM). SEM clearly demonstrated the adherence of nanoparticles to the cell surface. Incubation of D1 dendritic cells with nanoparticles containing antigen also resulted in morphological changes indicative of cell maturation similar to that observed when the cells were incubated with lipopolysaccharide. In contrast, cells incubated with antigen solution did not demonstrate such morphological changes and appeared similar to immature cells that had not been exposed to antigen.

Animals↗
PubMed2002

Effects of formulation variables on characteristics of poly (ethylcyanoacrylate) nanocapsules prepared from w/o microemulsions.

The effect of several formulation variables on some of the physico-chemical characteristics of poly (ethyl cyanoacrylate) (PECA) nanocapsules prepared by the interfacial polymerisation of biocompatible water-in-oil microemulsions was investigated. In all cases, yields were high (>90%) and the polydispersity in size of nanocapsules was narrow. The molecular weight of the nanocapsules formed was influenced by the pH of the aqueous component of the microemulsion, increasing with increasing pH. The size of the nanocapsules formed (ranging from around 130 to 180 nm) was a function of the ratio of the mass of monomer used to the water weight fraction of the microemulsion, increasing as this ratio was increased. This is due to the formation of a thicker polymer wall resulting from the increased mass of monomer available per unit interfacial area as this ratio is increased. The rate of release of insulin from nanocapsules was also influenced by this ratio, in agreement with its effect on wall thickness. This study demonstrates that many pharmaceutically relevant physico-chemical properties of poly (alkyl cyanoacrylate) (PACA) nanocapsules prepared by interfacial polymerisation of microemulsions can readily be manipulated by changing either the pH of the aqueous component, the water weight fraction of the microemulsion or the mass of monomer used for polymerisation.

Capsules↗
PubMed2002

Effects of meal consistency and ingested fluid volume on the intragastric distribution of a drug model in humans--a magnetic resonance imaging study.

BACKGROUND: Controlled delivery of drugs to the small intestine in relation to emptying of an ingested meal is important in various pathophysiological conditions. We investigated the effects of different food consistencies and the amount of co-ingested liquid on the intragastric distribution of a contrast marker. METHODS: Five healthy subjects received four meals (each 650 kcal: A, mashed potato with 100 mL water; B, rice with 100 mL water; C, hamburger meal with 100 mL water; D, hamburger meal with 300 mL water). A capsule filled with gadolinium tetra-azacyclododecane tetra-acetic acid solution (as contrast marker) was ingested following meal termination, and its intragastric distribution was assessed by magnetic resonance imaging. RESULTS: Initially, marker distribution was confined to the fundus, and subsequently extended along the inner curvature of the stomach. The maximum distribution volume of the marker was lower in meal A than in meal B (P < 0.05). No differences in marker distribution were observed when the hamburger meal was given with 100 or 300 mL water. CONCLUSIONS: The intragastric distribution kinetics of the marker gadolinium tetra-azacyclododecane tetra-acetic acid appeared to depend on meal consistency, but not on the amount of water co-ingested. Three-dimensional magnetic resonance imaging allows detailed analysis of the intragastric distribution of a drug model in relation to meal emptying and intragastric meal distribution.

Adult↗