On the needle clogging of staked-in-needle pre-filled syringes: Mechanism of liquid entering the needle and solidification process.

Staked-in-needle prefilled syringes (SIN-PFS) are widely used for the parenteral administration of drug product solutions. During stability studies, clogging of the injection needle was observed in syringes filled with concentrated antibody solution. A prerequisite for this phenomenon is that liquid has entered the needle. In this study, we characterized the mechanism causing the entry and movement of liquid in the needle using neutron imaging without manipulating the container closure integrity of the syringe. The gas pressure difference between inside and outside of the syringe was identified as the major cause of liquid movement. The influence of external factors, such as temperature fluctuation and physical pressure on the stopper, were tested and were confirmed to have a relevant impact on the processes of liquid entering and moving inside the injection needle. In a second step, the solidification process of the liquid segments inside the needle via solvent evaporation was further investigated, and the process was found to be dependent on storage time, environmental climate and interaction between the drug product solution and the needle surface. The presence of air/liquid segments was identified as a further factor for the stochastic behavior of needle clogging. For the first time, this fundamental mechanism behind the needle clogging issue was investigated in depth and the results will help to reduce the defect rate for clogged SIN-PFS products.

Clogging in staked-in needle pre-filled syringes (SIN-PFS): Influence of water vapor transmission through the needle shield.

Staked-in needle pre-fillable syringes (SIN-PFS) are a convenient delivery system widely established in the growing pharmaceutical market. Under specific storage conditions, the needle of PFS containing high concentration drug product (DP) solution is prone to clogging, which prevents administration of the liquid. The purpose of this study is to clarify the clogging phenomenon of SIN-PFS and to elucidate the role of water vapor transmission via the needle shield. The presence of liquid within needles is a prerequisite condition for clogging and was investigated non-invasively by neutron imaging (NI) to confirm that liquid can migrate into the needle under certain processing conditions. The water vapor transmission rate (WVTR) of different needle shields was measured and the impact of temperature and relative humidity (rH) on the WVTR was investigated on sheets with the same composition as used in commercial needle shields. Our study clearly showed that the partial vapor pressure difference (ΔPP) across the needle shield is the dominant driving factor for water vapor transmission. A linear correlation between ΔPP and WVTR was found and a model to predict the water vapor transmission for PFS under specific storage conditions was developed. The impact of the WVTR on needle clogging was confirmed by clogging tests performed on SIN-PFS stored under different conditions. Thereby, we clearly show that high water loss induced by higher WVTR can be correlated to an increased occurrence of needle clogging. In conclusion, the WVTR of the needle shield plays a key role in needle clogging and the established WVTR model can be employed to assess the clogging risk for product development.

Elastic modulus and fracture strength evaluation on the nanoscale by scanning force microscope experiments.

This work first reviews the capability of scanning force microscopy (SFM) to perform experiments with forces in a wide range, from low non-contact forces to high contact forces which induce mechanical deformations in the substrate. In analogy to fracture strength evaluation, as established in materials science, SFM is used to exert forces on pillars with nanometer dimensions while the cantilever deformations are monitored quantitatively. Hence, it is possible to bend the pillars until the threshold for triggering fracture is reached, and to determine the mechanical properties at the different stages of this process. Using this novel approach, in combination with 'state of the art' nanofabrication to produce nanopillar arrays on silicon and silicon dioxide substrates, a number of experiments are performed. Furthermore, quantitative measurements of the fracture strength of Si and of the SiO2/Si interface and E-modulus are presented. To analyze the experimental data obtained in the different experimental procedures and modes, finite element method calculations were used. The methods introduced herein provide a versatile toolbox for addressing a wide range of scientific problems and for applications in materials science and technology.

Energy level alignment at metal-octaethylporphyrin interfaces.

We studied the electronic structure of copper-octaethylporphyrin (CuEOP) adsorbed on three metal surfaces--Ag(001), Ag(111), and Cu(111)--by means of ultraviolet photoelectron spectroscopy (UPS). The adsorption-induced work function shifts saturate roughly beyond two monolayers. The saturation values are substrate dependent, negative, and range from -1.30 to -0.85 eV. This shift is larger than that for tetraphenylporphyrins. The two highest occupied molecular orbitals (HOMO and HOMO-1) of the organic are clearly resolved in the UPS spectra. The origin of the negative work function shift is discussed.

Molecular assembly and self-assembly: molecular nanoscience for future technologies.

In this review the emerging science of single molecules is discussed in the perspective of nanoscale molecular functions and devices. New methods for the controlled assembly of well-defined molecular nanostructures are presented: self assembly and single molecular positioning. The observation and selective modification of conformation, electronics, and molecular mechanics of individual molecules and molecular assemblies by scanning probes is demonstrated. To complement this scientific review, some of the possible consequences and visions for future developments are discussed, as far as they derive from the presented systems. The prospects of nanoscale science to stimulate technological evolution are exemplified.