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Narcoleptic patients suffer frequently from obesity and type II diabetes. Most patients show a deficit in the energy balance regulating orexinergic system. Nevertheless, it is not known, why narcoleptic patients tend to be obese. We examined 116 narcoleptic patients and 80 controls with the structured interview for anorectic and bulimic eating disorders (SIAB) to test the hypothesis that typical or atypical eating attacks or eating disorders may be more frequent in narcoleptic patients. No difference in the current prevalence of eating disorders bulimia nervosa, binge eating disorder, or anorexia nervosa was found, nor was the frequency of eating attacks higher in the narcolepsy group. We conclude that present eating disorders and eating attacks as defined in DSM IV are not the reason for the observed differences in body composition. Additional factors, such as basal metabolic rates and lifestyle factors need to be considered.

The aim of the present study was to characterize pegylated nanoparticles (NPs) for their microporosity and study the effect of microporosity on drug release kinetics. Blank and drug-loaded NPs were prepared from three different pegylated polymers, namely, poly(ethylene glycol)1%-graft-poly(D,L)-lactide, poly(ethylene glycol)5%-graft-poly(D,L)-lactide, and the multiblock copolymer (poly(D,L)-lactide-block-poly(ethylene glycol)-block-poly(D,L)-lactide)n. These NPs were characterized for their microporosity using nitrogen adsorption isotherms. NPs of the multiblock copolymer showed the least microporosity and Brunauer-Emmett-Teller (BET) surface area, and that of PEG1%-g-PLA showed the maximum. Based on these results, the structural organization of poly(D,L)-lactide (PLA) and poly(ethylene glycol) (PEG) chains inside the NPs was proposed and was validated with differential scanning calorimetry (DSC) and X-ray photoelectron spectroscopy (XPS) surface analysis. An in vitro drug release study revealed that PEG1%-g-PLA NPs exhibited slower release despite their higher surface area and microporosity. This was attributed to the presence of increased microporosity forming tortuous internal structures, thereby hindering drug diffusion from the matrix. Thus, it was concluded that the microporous structure of NPs, which is affected by the molecular architecture of polymers, determines the release rate of the encapsulated drug.

kappa-Carrageenan is known as a novel pelletization aid in manufacturing of pellets by extrusion/spheronization. The implentation of kappa-carrageenan as a pelletization aid can overcome several disadvantages of commonly used microcrystalline cellulose (MCC) such as lacking disintegration and adsorption of several actives. The aim of this study was to compare different types of carrageenans from different suppliers: one iota-, five kappa-, and one lambda-carrageenan. The kappa-carrageenans had the best pelletization behavior. Four of the five tested kappa-carrageenans resulted in pellets with acceptable shapes, sizes, and size distributions using a high drug load of 80% hydrochlorothiazide. These pellets have similar properties over a wide range of water contents ranging from 90 to 105%. The filler, dicalcium phosphate, affected the pelletization process and the pellet properties of all investigated kappa-carrageenans.

The aim of this study was to systematically evaluate the pelletization process parameters of kappa-carrageenan-containing formulations. The study dealt with the effect of 4 process parameters--screw speed, number of die holes, friction plate speed, and spheronizer temperature--on the pellet properties of shape, size, size distribution, tensile strength, and drug release. These parameters were varied systematically in a 2(4) full factorial design. In addition, 4 drugs--phenacetin, chloramphenicol, dimenhydrinate, and lidocaine hydrochloride--were investigated under constant process conditions. The most spherical pellets were achieved in a high yield by using a large number of die holes and a high spheronizer speed. There was no relevant influence of the investigated process parameters on the size distribution, mechanical stability, and drug release. The poorly soluble drugs, phenacetin and chloramphenicol, resulted in pellets with adequate shape, size, and tensile strength and a fast drug release. The salts of dimenhydrinate and lidocaine affected pellet shape, mechanical stability, and the drug release properties using an aqueous solution of pH 3 as a granulation liquid. In the case of dimenhydrinate, this was attributed to the ionic interactions with kappa-carrageenan, resulting in a stable matrix during dissolution that did not disintegrate. The effect of lidocaine is comparable to the effect of sodium ions, which suppress the gelling of carrageenan, resulting in pellets with fast disintegration and drug release characteristics. The pellet properties are affected by the process parameters and the active pharmaceutical ingredient used.

kappa-Carrageenan is a new pelletisation aid for the wet extrusion/spheronisation process. Its promising behavior during pelletisation offers a potential replacement of the commonly used microcrystalline cellulose in several formulations. Due to its high water binding, the drying step of the pelletisation has gained increasing attention. Therefore, a systematic investigation of the effect of drying conditions on pellet properties was the aim of this study. Pellets with different formulations were dried in fluid bed, circulation-, and vacuum oven and then characterized by mean dissolution time, tensile strength and disintegration time. Increasing the temperature and duration of the drying process decreased the mean dissolution time, tensile strength and disintegration time of the pellets. The observed effects were attributed to a cautious decomposition of the kappa-carrageenan above 70 degrees C. Furthermore an ionic interaction between calcium ions of dicalciumphosphate and sulfate ester groups of kappa-carrageenan affected the pellet properties like drug release.

The pore hierarchy of a hierarchical porous SiO2 with 14 nm spherical mesopores and 3 nm worm-like pores (KLE1C16) is studied by small-angle neutron scattering (SANS) in combination with in-situ nitrogen sorption at 77 K. A novel setup is used developed at Hahn-Meitner Institute, Berlin. It is demonstrated that in these materials indeed all of the large mesopores are connected through the smaller ones, thus providing invaluable insights into the general phenomenon of pore connectivity in mesoporous materials.

Microcrystalline cellulose (MCC) is commonly used as an excipient in extrusion/spheronisation process. However, MCC has several disadvantages as lack of disintegration and drug adsorption. Therefore, kappa-carrageenan was investigated to substitute MCC in pelletising processes. Formulations with 20% of pelletisation aid (kappa-carrageenan or MCC) and acetaminophen as a model drug have been produced. Different fillers (lactose, mannitol, maize starch and dicalciumphosphate dihydrate) at fractions of 0, 20, 40 and 80% were evaluated and the properties of the resulted pellets were determined (e.g. yield, aspect ratio, mean Feret diameter, 10% interval fraction, tensile strength and release profile). kappa-Carrageenan has proven to be a suitable substitute as pellets with sufficient quality were produced. The pellet batches of different formulations were characterised by high yield, spherical pellet shape and narrow pellet size distribution. The distinguished behaviour between kappa-carrageenan and MCC pellets was the lower tensile strength and the faster release of kappa-carrageenan pellets. For the various types and fractions of fillers only minor effects to the pelletisation process and pellet properties were noticed. From the practical view these effects are neglectable indicating a robust formulation and process.

The extrusion/spheronisation process is an established technique to produce pellets for pharmaceutical applications. Microcrystalline cellulose (MCC) is being usually used as a pelletisation excipient in the extrusion process. However, MCC has some disadvantages, e.g. lack of disintegration and prolonged drug dissolution. Therefore, kappa-carrageenan was investigated as a substitute for MCC to overcome such disadvantages. A fixed ratio of kappa-carrageenan (20%) was combined with different fillers (lactose, mannitol, maize starch and dicalciumphosphate dihydrate) and different drugs (acetaminophen, theophylline, mesalamine and hydrochlorothiazide) in several formulations. Some pellet properties (yield, aspect ratio, mean Feret diameter, 10% interval fraction, tensile strength and dissolution profile) were determined. Most formulations resulted in pellets of a sufficient quality with respect to size, size distribution and shape independent of the incorporated fillers and drugs. In contrast to MCC pellets, the release profile of kappa-carrageenan pellets was much less affected by the solubility of the drug. Generally, kappa-carrageenan pellets owned fast disintegration and fast drug release in contrast to MCC pellets.

The generation of porous silica with hierarchically organized bimodal mesoporosity of adjustable size and well-defined shape was investigated by using surfactant mixtures and the nanocasting procedure (liquid crystalline templating). A systematic study of combinations of various block copolymers (Pluronics F127, KLE (poly(omega-hydroxypoly(ethylene-co-butylene)-co-poly(ethylene oxide))) and SE (PS-co-PEO)) with smaller surfactants (Pluronics P123, C16mimCl, and CTAB) revealed that hierarchical bimodal mesopore architectures could only be obtained by the usage of block copolymers with a strong hydrophilic-hydrophobic contrast, such as KLE and SE, giving rise to pores between 6 and 22 nm. Furthermore, the ionic liquid (IL) C16mimCl appeared to have advantageous templating properties, resulting in 2-3-nm pores being located between the block copolymer mesopores, whereas phase separation was observed for Pluronics and CTAB as small templates. Thereby, the study provided also general insights into the mixing and co-self-assembly behavior of block copolymers and ionic surfactants in water and confirmed the special templating properties of ILs, as recently proposed. In addition to the bimodal mesoporosity, additional tunable macroporosity was created by the presence of poly(styrene) or poly(methyl methacrylate) spheres, leading to well-defined trimodal hierarchical pore architectures with the small pores being located in the walls of the respective larger pores. As a major improvement, due to the pore hierarchy, these large-pore materials showed relatively large surface areas and pore volumes, and the size of densely packed macropores could even be decreased down to 90 nm. The materials were characterized by electron microscopy, small-angle X-ray scattering, and nitrogen sorption using a proper NLDFT (nonlocal density functional theory) approach for calculations of the pore size distribution in the entire range of micro- and mesopores.

We report results of nitrogen and argon adsorption experiments performed at 77.4 and 87.3 K on novel micro/mesoporous silica materials with morphologically different networks of mesopores embedded into microporous matrixes: SE3030 silica with worm-like cylindrical channels of mode diameter of approximately 95 angstroms, KLE silica with cage-like spheroidal pores of ca. 140 angstroms, KLE/IL silica with spheroidal pores of approximately 140 angstroms connected by cylindrical channels of approximately 26 angstroms, and, also for a comparison, on Vycor glass with a disordered network of pores of mode diameter of approximately 70 angstroms. We show that the type of hysteresis loop formed by adsorption/desorption isotherms is determined by different mechanisms of condensation and evaporation and depends upon the shape and size of pores. We demonstrate that adsorption experiments performed with different adsorptives allow for detecting and separating the effects of pore blocking/percolation and cavitation in the course of evaporation. The results confirm that cavitation-controlled evaporation occurs in ink-bottle pores with the neck size smaller than a certain critical value. In this case, the pressure of evaporation does not depend upon the neck size. In pores with larger necks, percolation-controlled evaporation occurs, as observed for nitrogen (at 77.4 K) and argon (at 87.3 K) on porous Vycor glass. We elaborate a novel hybrid nonlocal density functional theory (NLDFT) method for calculations of pore size distributions from adsorption isotherms in the entire range of micro- and mesopores. The NLDFT method, applied to the adsorption branch of the isotherm, takes into account the effect of delayed capillary condensation in pores of different geometries. The pore size data obtained by the NLDFT method for SE3030, KLE, and KLE/IL silicas agree with the data of SANS/SAXS techniques.

The current study pursues the suitability of different types of carrageenan as a novel extrusion aid. The aim was to find out a suitable substitution to the commonly used microcrystalline cellulose (MCC). The types of kappa-carrageenan were found to be the most appropriate material and the required fraction to produce acceptable pellets in the formulation was determined. The investigation showed that 5% of kappa-carageenan was necessary to produce pellets without MCC. Similar formulations produced with MCC or kappa-carrageenan were compared with respect to size and shape of the pellets. kappa-Carrageenan required higher water content for the formation of pellets, but the formulation was more robust as the optimal range of water content was much broader. Hence, kappa-Carrageenan seems to be a suitable and promising extrusion aid. The study showed that the substitution of MCC by kappa-carrageenan in formulations is possible and the produced pellets were of high quality.

Lymphocytotoxicity to autologous or allogeneic synovial cells and Chang cells was studied in 27 patients with rheumatoid arthritis (RA), in 5 patients with osteoarthrosis of the hip or knee and in 17 healthy controls. Ficoll gradient-separated lymphocytes from the peripheral blood, T cells and non-T cells were used as effector cells. T lymphocytes were isolated as E-rosette forming cells 10 percent of which carried Fc- receptors. The differential counts for T and B cells in the peripheral blood of the RA and osteoarthrosis patients were approximately the same as in the blood of the healthy controls. The counts of Fc-receptor-bearing cells in the RA patients were, however, significantly higher. Cytotoxic reactivity of lymphocytes from RA patients, osteoarthrosis patients or healthy controls to synovial cells of autologous or allogeneic origin could not be demonstrated in our study, in which 125I-iododeoxyuridine labelled target cells were used in the microcytotoxicity test of Cohen et al. However, lymphocytes of the peripheral blood showed an increased cytotoxicity to Chang cells, an effect for which Fc-receptor bearing cells were responsible. Serum did not affect the cytotoxicity of lymphocytes. The results are interpreted as demonstrating an enhanced natural killer (NK) cell activity in RA patients; they do not indicate a specific cell mediated immune reaction to synovial cells.