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Biomedical subjects

H Leuenberger

Publications and source records attributed to H Leuenberger.

At least 19 recordsLinked to original sources
PubMed1997

Preparation of liposomes encapsulating water-soluble compounds using supercritical carbon dioxide.

In this paper the development of a new preparation method of liposomes containing a water soluble marker (fluorescein isothiocyanate-dextran (FITC-dextran) or zinc phthalocyanine tetrasulfonic acid (TSZnPc) using supercritical carbon dioxide (called "the supercritical liposome method") is described. The apparatus used consisted of two main parts: the high-pressure part, in which the lipid components 1-palmitoyl-2-oleoylphosphatidylcholine (POPC) and cholesterol (Chol) (7:3 molar ratio) were dissolved under pressure in supercritical carbon dioxide, and a low-pressure part, in which the homogeneous supercritical solution is expanded and simultaneously mixed with the aqueous phase to yield liposomes encapsulating the water soluble marker. Addition of 7% absolute ethanol to carbon dioxide at 25 MPa and 60 degrees C and the use of a high-pressure recycling system during 30 min form the homogeneous solution with high reproducibility of both lipid components and resulted in an equal expansion profile (recovery after expansion versus time) of POPC and Chol. Incubation of the lipid components during 60 min at the above mentioned conditions generated only 3% degradation. The average size of the liposomes was about 200 nm and could not be influenced by the experimental conditions used. Optimal values for encapsulated volume (1.25 L/mol) and efficiency (20%) of the liposomes were obtained using statistical experimental design by using the water soluble marker TSZnPc and an encapsulation capillary with 5.0 cm length and 0.5 mm inner diameter. The total amount of ethanol used to obtain an encapsulation efficiency of 20% was 15-fold reduced compared to the ethanol injection method of Batzri and Korn (Biochim. Biophys. Acta 1973, 298, 1015-1019).

Carbon Dioxide↗
PubMed1996

An improved diffusion cell design for determining drug transport parameters across cultured cell monolayers.

An improved two-chamber diffusion cell was developed for the study of drug transport across cultured cell monolayers. The cell monolayer was grown on a horizontal support membrane of polycarbonate, which could be rotated providing theoretically predictable thicknesses of the diffusion boundary layer in the donor and the receiver solution as a function of rotation rate. Permeation measurements were performed using the support membrane with and without a cell monolayer. The Madin-Darby-Bovine-Kidney (MDBK) cell line was employed, and permeability coefficients of model solutes (salicylic acid, mannitol, testosterone) across the three distinct mass transport barriers (i.e., the cell monolayer, the support membrane, and the diffusion boundary layer) were determined. The permeability of the diffusion boundary layer followed the theoretical dependence on the rotation rate; absolute values, however, deviated from predictions. Permeability coefficients for all three transport barriers varied substantially between solutes. This variation was the strongest for the permeability coefficient for the cell monolayer and resulted in a varying relative significance of these three barriers in controlling permeation kinetics. This improved diffusion apparatus permits the measurement of unbiased permeability values of solutes across the cell monolayer, notably when the cell monolayer is not absolutely the rate-determining barrier.

Animals↗
PubMed1996

Albumin nanospheres as carriers for passive drug targeting: an optimized manufacturing technique.

PURPOSE: The purpose of this study was to develop a new method to produce albumin particles in the sub-200-nanometer range with a narrow size distribution and in a controlled and reproducible manner. METHODS: A new emulsion crosslinking method was developed using ultrasound and static mixing as homogenization steps and a central composite design was used to evaluate the influence of different process parameters on particle size, polydispersity and yield. RESULTS: Response surface analysis allowed the location of the most important factors. Of all the factors investigated, only the albumin concentration and the aqueous phase volume showed a significant influence on response parameters. Albumin nanospheres with sizes below 200 nm in diameter and very narrow size distributions were obtained in high yields ( > 80%). CONCLUSIONS: This study describes a new preparation method for albumin nanoparticles which are suitable for future drug targeting studies.

Cross-Linking Reagents↗
PubMed1995

Membrane modulated dissolution of oral drug delivery systems.

A kinetic model analogous to two chemical reactions occurring in series describes the dissolution behavior of tablets and pellets coated with either microporous or semipermeable membranes. Microporous membranes permit free water influx, but moderated core dissolution and dialytically controlled solution efflux. Semipermeable membranes allow osmotically limited water influx, moderated core dissolution, but relatively unimpeded solution efflux through a release orifice. An explanation is offered which illustrates why the systems perform similarly despite major differences in the membrane structure and need for a release orifice. Applications to literature examples and experimental evidence demonstrate the suitability of the model.

Acetaminophen↗
PubMed1995

Behavioural aspects of travellers in their use of malaria presumptive treatment.

The use of stand-by treatment for malaria by travellers depends on their knowledge, attitudes and behaviour. We examined the behavioural aspects of a cohort of travellers from Switzerland to low-risk malarial areas who, on recruitment, were provided with a kit containing medication for stand-by treatment, guidelines on the diagnosis of malaria, and materials for collection of blood samples for later confirmation of malaria. All subjects were urged to seek medical advice at the first signs of possible malarial symptoms. Illness (fever as the main indicator) was reported by 123 of the 1187 participants, often accompanied by shivering/chills (36.6%), headache (35.0%), gastrointestinal symptoms (69.9%), and myalgia and/or arthralgia (41.5%). Two-thirds of those ill failed to seek medical attention despite their symptoms and pretravel advice. Only 9 (7.3%) were actually beyond the reach of medical attention. The stand-by treatment was self-administered by 6 travellers, only one of whom had confirmed malaria. Two non-serious adverse events were reported. All users consulted a physician after administering the presumptive treatment. This stand-by approach is limited by inappropriate behaviour and poor malaria awareness among travellers. These negative factors can be mitigated by development of an improved kit containing a simple test for self-diagnosis.

Adult↗
PubMed1994

Large-scale production of liposomes containing monomeric zinc phthalocyanine by controlled dilution of organic solvents.

This work describes the development of an organic solvent dilution method suitable for the large scale manufacturing of small unilamellar liposomes containing the water-insoluble photosensitizer zinc phthalocyanine in the monomeric state. N-Methyl pyrrolidone (NMP)/tert-butyl alcohol was selected as water miscible organic phase in which the phospholipids 1-palmitoyl, 2-oleoylphosphatidylcholine (POPC), and 1,2-dioeloylphosphatidylserine (OOPS) and the dye were dissolved. This organic phase was mixed with an excess of a water phase using a dynamic mixing device, yielding reproducibly unilamellar liposomes with a mean size of 50-150 nm as measured with quasielastic light scattering. After concentration, the organic solvents were efficiently removed by cross-flow filtration. The liposomes were then sterile filtered and freeze-dried. A method to measure the aggregation state of the dye in the liposomes was developed. A stable lyophilized formulation containing monomeric liposomal ZnPc could be obtained by using a solution of ZnPc in NMP (2 mg/mL) and ZnPc/phospholipid (1:100 w/w ratio) and performing concentration and dialysis at 4 degrees C and lyophilization in presence of a mixture of lactose and phospholipid (5:1 w/w ratio).

Chromatography, Gas↗
PubMed1992

Formation of a tablet: a site and bond percolation phenomenon.

The concepts of percolation theory are used to elucidate the formation of a tablet by compression of particulate matter. The process of compaction can be considered as a combination of site and bond percolation phenomena. Because of effects of different particle size and shape of the particles in a powder bed and effects of brittle fracture and plastic flow, moisture content of the powder, and finite size of the tablet, no sharp percolation thresholds are expected. Thus, it is interesting to test the validity of the fundamental equation of percolation theory: the power law X = S(p - pc)q, where X is the system property, S is the scaling factor, p is the site occupation or bond formation probability, and q is the critical exponent. This model is, in certain cases, only rigorously valid close to the percolation threshold (range, [+/- 0.1 pc]). Combination of the Heckel equation with an equation derived earlier for the properties (X) of tensile strength (sigma t) and deformation hardness (P) yields a power law with q = 1, S'(sigma t) = sigma tmax/(1 - pc), and S(P) = Pmax/(1 - pc). With respect to the simplifying assumptions made, the power law agrees well with the experimental results obtained. Substantial improvements in the interpretation of the compression-compaction process are possible with these findings, and some interpretations differ from previous ones in earlier publications.

Chemistry, Pharmaceutical↗
PubMed1991

Matrix type controlled release systems: I. Effect of percolation on drug dissolution kinetics.

Matrix type controlled release tablets were prepared by compression of binary mixtures of a soluble brittle model drug (caffeine) and a plastic matrix substance (ethyl cellulose). The drug content of the tablets was varied from 10% to 100% (weight/weight) and the drug dissolution from one flat side of the tablets was studied. By means of percolation theory the release kinetics could be explained over the whole range of drug loadings. For low drug concentrations up to the lower percolation threshold the release was incomplete because most of the drug was encapsulated by the matrix substance. For drug loadings between the lower and the upper percolation threshold the release was matrix-controlled. For high drug loadings a change to zero order dissolution kinetics was observed. Close to the percolation threshold the diffusion coefficient obeys a scaling law, from which a simple equation to estimate the value of the lower percolation threshold was derived and applied to the measured dissolution data. The critical porosity (lower percolation threshold) was found to be 0.35, corresponding to a drug content of about 28% (weight/weight).

Caffeine↗
PubMed1990

Percolation theory and compactibility of binary powder systems.

Defined size fractions of polyethyleneglycol powder (MW = 10,000) were mixed with defined size fractions of alpha-lactose monohydrate in order to study the effect of compaction as a function of the weight ratios of the two excipients. For a precise control of the compression cycle, tablets were compressed on a Universal Testing Machine (Zwick 1478). Tablet tensile strength sigma T was quantified as a function of compressional stress sigma c and relative density rhor r using a two-parameter model with sigma Tmax = maximal tensile strength at zero porosity and gamma = compressibility. The results have been analyzed on the basis of the percolation theory. As soon as the component with the lower mechanical stability is percolating the powder system, tablet hardness is controlled entirely by this component. The percolation threshold is a function of the geometrical arrangement of the particles in the compressed powder system. The expected two percolation thresholds can be distinguished as a function of the composition weight ratios if the particle size distributions of the two components differ enough.

Ascorbic Acid↗