51.
Elm, Marie
(författare)
LÄR-UT : bättre läkemedelshantering för äldre
2007
Rapport (övrigt vetenskapligt/konstnärligt) abstract
Målet med projektet LÄR-UT är att ta fram en modell för bättre läkemedelshantering för äldre samt att utbilda sjuksköterskor inom kommunal hälso- och sjukvård till handledare.
52.
Elversson, Jessica, et al.
(författare)
An atomic force microscopy approach for assessment of particle density applied to single spray-dried carbohydrate particles
2007
Ingår i: Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0022-3549 .- 1520-6017. ; 96:4, s. 905-912
Tidskriftsartikel (refereegranskat) abstract
To evaluate an atomic force microscopy (A-FM) approach for effective density analysis of single spray dried carbohydrate particles in order to investigate the internal structure of the particles. In addition, the AFM method was compared to an established technique, that is gas pycnometry. Resonant frequency AFM analysis was employed for determination of the mass of individual particles of spray-dried lactose, mannitol, and a mixture of sucrose/dextran (4:1). The effective particle density was calculated using the diameter of the spherical particles obtained from light microscopy. The apparent particle density was further analyzed with gas pycnometry. It was observed by microscopy that particles appeared either ""solid"" or ""hollow."" A solid appearance applied to an effective particle density close to the true density of the material, whereas a density around 1 g/cm(3) corresponded to a hollow appearance. However, carbohydrates, which crystallized during spray drying, for example, mannitol appeared solid but the 3 average effective particle density was 0.95 g/cm, indicating a continuous but porous structure. AFM measurements of effective particle density corroborate the suggestion of differences in particle structure caused by the varying propensity of carbohydrates to crystallize during spray drying, resulting in mainly either amorphous hollow or crystalline porous particles.
53.
Engström, Sven, 1951, et al.
(författare)
Cubic, sponge, and lamellar phases in the glyceryl monooleyl ether-propylene glycol-water system
2007
Ingår i: Langmuir. - 1520-5827 .- 0743-7463. ; 23:20, s. 10020-10025
Tidskriftsartikel (refereegranskat) abstract
The phase behavior of 1-glyceryl monooleyl ether (GME) in mixtures of propylene glycol (PG) and water was investigated by visual inspection, polarization microscopy, small-angle X-ray diffraction, and conductance measurements. A phase diagram, based on over 200 samples of the ternary system GME-PG-water, was constructed at 20 degrees C. Without PG, GME forms a reverse micellar phase with up to 10 wt % water and a reverse hexagonal liquid-crystalline phase between 10 and 25 wt % water, a phase that can coexist with excess water. If PG is added in amounts exceeding about 10 wt %, then cubic and lamellar liquid-crystalline phases start to form. A cubic phase, belonging to space group Pn3m, can coexist with excess PG-water mixtures. If even more PG is added, then the cubic phase is transformed into a sponge phase. A lamellar phase forms at water contents between 10 and 15 wt % and with widely differing PG/GME weight ratios. We postulate that the phase behavior is caused by the fact that PG makes the interfacial region between self-assembled GME and PG-water less negatively curved, which in turn allows for the formation of the new phases. The phase behavior obtained for the GME system shows a striking similarity with the phase behavior of the corresponding system in which the GME has been replaced by the ester, 1-glycerol monooleate (GMO), differing only in one extra carbonyl oxygen. The major difference is the lower amount of water present in the GME phases, an effect that is mainly due to the more hydrophobic character of GME compared to that of GMO.
54.
Fanta, Samuel, et al.
(författare)
Developmental pharmacokinetics of ciclosporin : a population pharmacokinetic study in paediatric renal transplant candidates
2007
Ingår i: British Journal of Clinical Pharmacology. - : Wiley. - 0306-5251 .- 1365-2125. ; 64:6, s. 772-784
Tidskriftsartikel (refereegranskat) abstract
Aims To use population pharmacokinetic modelling to characterize the influence of developmental and demographic factors on the pharmacokinetic variability of ciclosporin. Methods Pharmacokinetic modelling was performed in NONMEM using a dataset comprising 162 pretransplant children, aged 0.36–17.5 years. Ciclosporin was given intravenously (3 mg kg−1) and orally (10 mg kg−1) on separate occasions followed by blood sampling for 24 h. Results A three-compartment model with first-order absorption without lag-time best described the pharmacokinetics of ciclosporin. The most important covariate affecting systemic clearance (CL) and distribution volume (V) was body weight (BW; scaled allometrically), responsible for a fourfold difference in uncorrected ciclosporin CL and a sixfold difference in ciclosporin V. The other significant covariates, haematocrit, plasma cholesterol and creatinine, were estimated to explain 20–30% of interindividual differences in CL and V of ciclosporin. No age-related changes in oral bioavailability or in BW-normalized V were seen. The BW-normalized CL (CL/BW) declined with age and prepubertal children (<8 years) had an approximately 25% higher CL/BW than did older children. Normalization of CL for allometric BW (BW3/4) removed its relationship to age. Conclusion The relationship between CL and allometric BW is consistent with a gradual reduction in relative liver size, until adult values, and a relatively constant CYP3A4 content in the liver from about 6–12 months of age to adulthood. Ciclosporin oral bioavailability, known previously to display large interindividual variability, is not influenced by age. These findings can enable better individualization of ciclosporin dosing in infants, children and adolescents.
55.
Fatouros, Dimitrios G., et al.
(författare)
Structural development of self nano emulsifying drug delivery systems (SNEDDS) during In vitro lipid digestion monitored by small-angle x-ray scattering
2007
Ingår i: Pharmaceutical Research. - : Springer Science and Business Media LLC. - 1573-904X .- 0724-8741. ; 24:10, s. 1844-1853
Tidskriftsartikel (refereegranskat) abstract
Purpose. To investigate the structural development of the colloid phases generated during lipolysis of a lipid-based formulation in an in vitro lipolysis model, which simulates digestion in the small intestine. Materials and Methods. Small-Angle X-Ray scattering (SAXS) coupled with the in vitro lipolysis model which accurately reproduces the solubilizing environment in the gastrointestinal tract and simulates gastrointestinal lipid digestion through the use of bile and pancreatic extracts. The combined method was used to follow the intermediate digestion products of a self nano emulsified drug delivery system (SNEDDS) under fasted conditions. SNEDDS is developed to facilitate the uptake of poorly soluble drugs. Results. The data revealed that a lamellar phase forms immediately after initiation of lipolysis, whereas a hexagonal phase is formed after 60 min. The change of the relative amounts of these phases clearly demonstrates that lipolysis is a dynamic process. The formation of these phases is driven by the lipase which continuously hydrolyzes triglycerides from the oil-cores of the nanoemulsion droplets into mono- and diglycerides and fatty acids. We propose that this change of the over-all composition of the intestinal fluid with increased fraction of hydrolyzed nanoemulsion induces a change in the composition and effective critical packing parameter of the amphiphilic molecules, which determines the phase behavior of the system. Control experiments (only the digestion medium) or the surfactant (Cremophor RH 40) revealed the formation of a lamellar phase demonstrating that the hexagonal phase is due to the hydrolysis of the SNEDDS formulation. Conclusion. The current results demonstrate that SAXS measurements combined with the in vitro dynamic lipolysis model may be used to elucidate the processes encountered during the digestion of lipid-based formulations of poorly soluble drugs for oral drug delivery. Thus the combined methods may act as an efficient screening tool.
56.
Fernández, Estíbaliz L., et al.
(författare)
Expression of ZnT-1 (Slc30al) and MT-1 (Mt1) in the conceptus of cadmium treated mice
2007
Ingår i: Reproductive Toxicology. - : Elsevier BV. - 0890-6238 .- 1873-1708. ; 24:3-4, s. 353-358
Tidskriftsartikel (refereegranskat) abstract
There are indications that Cd-induced malformations in rodents are related to a disrupted flux of Zn to the developing embryo. The aim of the present study was to detect ZnT-1 (Slc30al) and MT (Mt1) protein in structures within the decidua, yolk sac and embryo of mice and to determine whether Cd affects ZnT-1 or MT-1 gene expression in these tissues. ZnT-1 was detected in the placental labyrinth, in the ventral part around the floor plate, in the inner cell layers of the rhombencephalon and in the ventral area of the otic vesicle. MT protein was detected in the yolk sac and in the Surface ectoderm of some embryonic areas, such as the pharyngeal arches. ZnT-1 and MT-1 transcripts were most abundant in the decidua and yolk sac, whereas the abundance of these genes was relatively low in the embryo. Cd exposure down-regulated ZnT-1 and up-regulated MT-1 gene expression in all structures investigated, indicating that maternal Cd exposure may alter Zn homeostasis in the conceptus.
57.
Fichtner, Frauke, et al.
(författare)
Drug release from compacted single inert matrix agglomerates
2007
Ingår i: Journal of Drug Delivery Science and Technology. - 1773-2247. ; 17:4, s. 273-277
Tidskriftsartikel (refereegranskat) abstract
The effect of compaction on the drug release from single, sodium chloride loaded, microcrystalline cellulose agglomerates of different porosities was investigated in this study. The drug release from uncompacted agglomerates and from agglomerates regained from tablets compacted at a range of different compaction pressures was monitored measuring the conductivity of the dissolution medium in a recirculation flow-through system. The drug release profiles were described using the mean dissolution time (MDT), the variation of dissolution time (VDT) and the relative dispersion coefficient (RD). It was found that depending on physical structure changes of the matrix, the drug release rate of compacted agglomerates could be enhanced or retarded in comparison with uncompacted agglomerates. The retardation is suggested to be due to a densification of the matrix and the enhancement due to a crack formation in the external surface of the matrix.
58.
Fichtner, Frauke, et al.
(författare)
Effect of preparation method on compactability of paracetamol granules and agglomerates
2007
Ingår i: International Journal of Pharmaceutics. - : Elsevier BV. - 0378-5173 .- 1873-3476. ; 336:1, s. 148-158
Tidskriftsartikel (refereegranskat) abstract
The objective of this study was to investigate the effect of fracture strength of paracetamol particles on their compactability. For this purpose two series of paracetamol particles were prepared by crystal agglomeration and by granulation using different solvents. A free flowing particle size fraction of all types of particles was characterized with respect to their shape, degree of agglomeration and single fracture strength. The powders were compressed to tablets and the compression mechanism of the particles and the evolution in tablet micro-structure were assessed by compression parameters derived from the Heckel and Kawakita equations and by a tablet permeabililty coefficient. Tablet tensile strength and porosity were determined. The degree of deformation and fragmentation during compression varied between agglomerates and granules and was dependent on their failure strength. The granules varied in compactability with particle failure strength while the agglomerates showed limited variation. It is proposed that, the dominant mechanism of compression for the granules was permanent deformation while for the agglomerates it was fragmentation. It was thus found that the compression mechanism of the particles was dependent on both the degree of agglomeration and the particle failure strength.
59.
Fransén, Nelly, et al.
(författare)
Development and characterisation of interactive mixtures with a fine-particulate mucoadhesive carrier for nasal drug delivery
2007
Ingår i: European journal of pharmaceutics and biopharmaceutics. - : Elsevier BV. - 0939-6411 .- 1873-3441. ; 67:2, s. 370-376
Tidskriftsartikel (refereegranskat) abstract
The aim of this study was to investigate whether mucoadhesive interactive mixtures can be created using carrier particles in a size range appropriate for nasal administration, i.e. 10–50 μm. We also used theoretical models to investigate if homogeneity measurements can be used to evaluate the formation of interactive mixtures containing carrier particles in this size range. Sodium starch glycolate (SSG) was used as carrier material and sodium salicylate (SS) as the model fine-particulate drug. The size ranges of SSG particles and amounts of SS were varied to find the smallest carrier particle size and highest amount of drug that still resulted in an interactive mixture. Visual inspection of the mixtures by scanning electron microscopy showed that interactive mixtures could be formed with carrier particles as small as 30 μm and containing up to 4% (w/w) of SS. Comparisons with theoretical models highlighted the difficulties of using homogeneity measurements to determine if interactive mixtures were formed. The measured coefficients of variation (CV) for the amount of drug in the samples were low and inferior mixtures were associated with only a slight increase. It was thus concluded that mucoadhesive interactive mixtures can be created in an appropriate size range for nasal administration, but that visual inspection of these mixtures is initially necessary to confirm the formation of an interactive mixture.
60.
Fransén, Nelly, et al.
(författare)
The in vitro transport of dihydroergotamine across porcine nasal respiratory and olfactory mucosa and the effect of a novel powder formulation
2007
Ingår i: Journal of Drug Delivery Science and Technology. - 1773-2247. ; 17:4, s. 267-271
Tidskriftsartikel (refereegranskat) abstract
The objective was to investigate the transport of dihydroergotamine (DHE) across porcine nasal respiratory and olfactory mucosa and to evaluate the absorption enhancing effect of a novel dry powder formulation compared with a reference solution with the horizontal Ussing chamber method. The powder formulation was obtained by mixing micronized DHE particles and mucoadhesive carrier particles (sodium starch glycolate) to create an interactive mixture. The horizontal Ussing chamber method was chosen as the in vitro model since it provides the opportunity to apply a dry powder formulation and compare the transport across the two types of nasal mucosa. A histological evaluation confirmed that the mucosa had been correctly isolated. The results showed no significant difference in the absorption from the powder formulation compared with the reference solution, but the transport of DHE was significantly higher across olfactory mucosa than across respiratory mucosa. This may be explained by facilitated transport through paracellular transfer along the olfactory nerve cells.
