Analysis of thin baked-on silicone layers by FTIR and 3D-Laser Scanning Microscopy.

Pre-filled syringes (PFS) and auto-injection devices with cartridges are increasingly used for parenteral administration. To assure functionality, silicone oil is applied to the inner surface of the glass barrel. Silicone oil migration into the product can be minimized by applying a thin but sufficient layer of silicone oil emulsion followed by thermal bake-on versus spraying-on silicone oil. Silicone layers thicker than 100nm resulting from regular spray-on siliconization can be characterized using interferometric profilometers. However, the analysis of thin silicone layers generated by bake-on siliconization is more challenging. In this paper, we have evaluated Fourier transform infrared (FTIR) spectroscopy after solvent extraction and a new 3D-Laser Scanning Microscopy (3D-LSM) to overcome this challenge. A multi-step solvent extraction and subsequent FTIR spectroscopy enabled to quantify baked-on silicone levels as low as 21-325µg per 5mL cartridge. 3D-LSM was successfully established to visualize and measure baked-on silicone layers as thin as 10nm. 3D-LSM was additionally used to analyze the silicone oil distribution within cartridges at such low levels. Both methods provided new, highly valuable insights to characterize the siliconization after processing, in order to achieve functionality.

Silicone rod extraction followed by liquid desorption-large volume injection-programmable temperature vaporiser-gas chromatography-mass spectrometry for trace analysis of priority organic pollutants in environmental water samples.

In this study a priority organic pollutants usually found in environmental water samples were considered to accomplish two extraction and analysis approaches. Among those compounds organochlorine compounds, pesticides, phthalates, phenols and residues of pharmaceutical and personal care products were included. The extraction and analysis steps were based on silicone rod extraction (SR) followed by liquid desorption in combination with large volume injection-programmable temperature vaporiser (LVI-PTV) and gas chromatography-mass spectrometry (GC-MS). Variables affecting the analytical response as a function of the programmable temperature vaporiser (PTV) parameters were firstly optimised following an experimental design approach. The SR extraction and desorption conditions were assessed afterwards, including matrix modification, time extraction, and stripping solvent composition. Subsequently, the possibility of performing membrane enclosed sorptive coating extraction (MESCO) as a modified extraction approach was also evaluated. The optimised method showed low method detection limits (3-35 ng L(-1)), acceptable accuracy (78-114%) and precision values (<13%) for most of the studied analytes regardless of the aqueous matrix. Finally, the developed approach was successfully applied to the determination of target analytes in aqueous environmental matrices including estuarine and wastewater samples.

Extractables/leachables from plastic tubing used in product manufacturing.

While the ability of packaging systems to contribute leached substances to finished drug products is well established, increasing interest is being focused on the potential contamination of drug substances by plastic materials encountered during their production. The direct contact of such plastic parts (such as tubing, gaskets, filters and temporary storage containers) with the drug substance at some point in its production raises the possibility that plastic-related contaminants (leachables) may be present in the finished drug product. In this study, eight tubing materials potentially encountered in pharmaceutical production facilities, including six silicone materials and two Santoprene materials, were characterized for their extractable substances by static extraction coupled with comprehensive chemical characterization of the resulting extracts. Based on the extractables profiles thus generated, target leachables were identified for each tubing material. The accumulation of these target leachables was studied by subjecting the tubing to dynamic flow, simulated use extractions. The primary organic extractables from the silicone tubing were a homologous series of silicone oligomers, with most of the tubings demonstrating a unique distribution of oligomers. Several of the silicone tubings also possessed extractable dioctyl phthalate and dioctyl adipate. The primary organic extractables from the Santoprene-type tubing included a number of phthalates, a series of alkyl phenols and decomposition products of Irganox-type antioxidants. Inorganic extractables associated with many of the tubings included Ca, Mg, Zn and B. In general, the levels of targeted leachables extracted from the tubing materials under simulated use (flow) conditions was much smaller than the total amount of these leachables in the tubing.

Polydimethylsiloxane rod extraction, a novel technique for the determination of organic micropollutants in water samples by thermal desorption-capillary gas chromatography-mass spectrometry.

A novel, simple and inexpensive approach to absorptive extraction of organic compounds from environmental samples is presented. It consists of a polydimethylsiloxane rod used as an extraction media, enriched with analytes during shaking, then thermally desorbed and analyzed by GC-MS. Its performance was illustrated and evaluated for the enrichment of sub- to ng/l of selected chlorinated compounds (chlorobenzenes and polychlorinated biphenyls) in water samples. The new approach was compared to the stir bar sorptive extraction performance. A natural ground water sample from Bitterfeld, Germany, was also extracted using both methods, showing good agreement. The proposed approach presented good linearity, high sensitivity, good blank levels and recoveries comparable to stir bars, together with advantages such as simplicity, lower cost and higher feasibility.

Silylating reagents: a powerful tool for the construction of isosteric analogs of highly branched odorants.

We have discovered that alpha-[dimethyl(thexyl)silyl]acetaldehyde (= [dimethyl(1,1,2-trimethylpropyl)silyl]acetaldehyde; 31) has a strong, woody odor. Structural analysis has shown resemblance to known odorants with similar organoleptic properties. On the basis of structure-odor relationships, new and more-powerful woody and ambery sila odorants were prepared. Further derivatization led to a set of compounds with very interesting organoleptic properties. Selected chiral compounds were also prepared stereoselectively. The influence of the absolute configuration on the olfactory properties was in agreement with theoretical assumptions. We also designed other groups of organosilicon odorants. The compounds discovered can be obtained in a few simple steps from commercially available reagents, and may find application in the fragrance and flavor industry. Their structures provide interesting data for further research on structure-odor relationships.

Ion mobility detection of polydimethylsilicone oligomers following supercritical fluid chromatographic separation.

A mixture of polydimethylsilicones (Dow Corning 200), average molecular weight 2000 a.m.u., was separated by simultaneous density and temperature-programmed supercritical fluid chromatography and detected by ion mobility detection. Ion mobility spectra were captured by Fourier transform ion mobility spectrometry. Using information from these spectra it was possible to selectively detect a single compound in the complex mixture. A detector temperature investigation demonstrated that, for the efficient transfer of high-molecular-weight compounds from the column to the detector, the interface to the detector must be heated. Using a 50 microns I.D. column, a Guthrie-type restrictor and a detection temperature of 250 degrees C, as many as 70 oligomers were separated and detected.

Chemical and physical aspects of clinically applied silicones.

In conclusion, one can state that silicones are one of the most inert materials available for use in medical field today. They meet all the requirements for implants, summarized in table V, and can be considered as the ideal material for intraocular use, provided that the polymer is absolutely pure and free of any kind of residues. For silicone rubbers the following specifications have to be fulfilled: the material has to be free of reactive prepolymers and of catalyzers, the filler should be of the same chemical nature as the basic material and should be chemically bound to the backbone of the polymer, to avoid any kind of migration out of the polymer. For silicone oils, the following criteria are desirable: the oil has to be practically free of low molecular components, mainly cyclohexanes, the molecular weight distribution should be as small as possible and the oil should be free of catalysts.

Electron microscopy and microprobe analysis of dialysis contaminants.

A migration of plastic particles from haemodialysis circuit to blood has been recognized to be cause of storage inflammation. Its origin from segments of silicone tubing has been demonstrated by in vivo and in vitro experiments. A similar finding with a peculiar histology picture has been observed in patients who used only PVC and PU-PVC tubing. In this case too microprobe analysis revealed the presence of silicon (Si) in fibril inclusions of liver and spleen cells. TEM, SEM and EDS of cuprophane dialyzer perfusates filtered through Nuclepore revealed the presence of particles with an intense Si Ka. The release from the dialyzer of silicon containing contaminants seems to be an additional risk for uremic patients.