Standard Cartridge Research Articles

Investigation of long-term pressure on primary packaging materials and a biologic drug product for injection with a novel autoinjector concept.

Gerresheimer and Midas Pharma have developed a novel cartridge-based autoinjector concept in which the cartridge as primary packaging is under constant pressure. In this article standard cartridge primary packaging material of five different companies were analyzed for their behavior under long-term pressure. Materials of 3 glass manufacturers and 2 manufacturers for cartridge rubber parts were considered. Within the test program septum stability, septum piercing, glide forces (GF), break-loose forces (BLF), glass breaking as well as a regulatory approved and marketed antibody drug product under pressure were subject to analysis. Under pressure the cartridge septum bulge grew within the first 14 days and then relevantly slowed down. An accelerated study in different atmospheric conditions allowed to extrapolate values for 24 months storage, not showing any signs of decay or problematic septum bulge increase. Pierce forces were in normal ranges and septum rupture could not be observed at the end of 42 days of pressurization. GF and BLF were within acceptable ranges and changes due to pressure could not be observed. Lowest glass breaking pressures at 4922kPa turned out to be at least 3.5 times higher than pressures used in the autoinjector concept. Degradation of the Adalimumab antibody drug product due to pressure or device fluid pathway could not be observed with size exclusion chromatography, electrophoresis or sub-visible particles tested as a release testing in a GMP setting.

Pressure sensitive adhesives and paper spray-mass spectrometry for the collection and analysis of fentanyl-related compounds from shipping materials.

The rise of fentanyl and fentanyl analogs in the drug supply pose serious threats to public health. Much of these compounds enter the United States through shipping routes. Here we provide a method for fentanyl screening and analysis that utilizes pressure-sensitive adhesive (PSA) lined paper to recover drug residues from parcel-related surfaces. The paper used is commercially available repositionable notes (also called post-it or sticky notes). From this paper, mass spectra were obtained by paper spray-mass spectrometry (PS-MS), where PSA paper served as both a sampling and analysis substrate. Seven fentanyl-related compounds were analyzed: fentanyl, 4-anilino-N-phenethylpiperidine (4-ANPP), N,1-diphenethyl-N-phenylpiperidin-4-amine (phenethyl-4-ANPP), valerylfentanyl, 4-fluoroisobutyrylfentanyl (4-FIBF), carfentanil, and p-fluorofentanyl. These compounds were recovered by PSA paper and identified by PS-MS from packaging tape and plastic at 50 ng and from cardboard and shipping labels at 100 ng. The impact of cutting agents on PS-MS analysis of fentanyl analogs was explored. No trends of analyte suppression were found at high concentrations of the cutting agents caffeine, diphenhydramine, and lidocaine when recovered from surfaces. A cartridge that required no precise cutting of PSA paper prior to sampling or analysis was evaluated for use in PS-MS for fentanyl screening. Recovery and detection of fentanyl from plastic sheeting was demonstrated with this cut-free cartridge. The cut-free cartridge showed somewhat less consistency and lower analyte signal than the standard cartridge, but performance was suitable for potential screening applications. In combining PSA surface sampling with PS-MS for drug screening, both sampling and detection of fentanyl-related compounds is simple, rapid, and low-cost.

Survival dependence of 3D-printed temporary materials on the filler content.

The aim of the present study was the evaluation of the in vitro performance and fracture force of 3D-printed anterior implant-supported temporary partial dentures (TPDs) with different filler content. Identical anterior resin-based TPDs (tooth sites 11 to 13; n = eight per material) were 3D printed from methacrylate resins with different filler content. A cartridge polymethyl methacrylate (PMMA) material was used as a reference. After temporary cementation, combined thermal cycling and mechanical loading (TCML) was performed on all the restorations to mimic clinical application. Behavior during TCML and fracture force was determined, and failures were analyzed. Data were statistically investigated (Kolmogorov-Smirnov test, one-way ANOVA; post hoc Bonferroni, Kaplan-Meier survival; α = 0.05). Failure during TCML varied between three failures and total failure during loading time. Mean survival time varied between 93 ± 206 x 103 cycles and 329 ± 84 x 103 cycles. Significantly different survival cycles between the individual materials could be determined (Mantel Cox log-rank test: chi-square: 21,861; degrees of freedom (df) = 4, P < 0.001). A correlation between filler level and survival cycles could be found (Pearson: 0.186, P = 0.065). Fracture values of the surviving TPDs varied between 499 and 835 N. Failures were characterized by fracture of the connector (n = 24) followed by fractures at the abutment (n = 10). TDPs showed different filler-dependent survival. Individual 3D-printed materials provided comparable or even better performance than a standard cartridge system and might be sufficient for temporary application of at least half a year.

Modification of intraocular lens insertion using 4-flanged fixation with a standard cartridge and a 2.4 mm corneal incision in eyes with no capsular support.

A modification of intraocular lens (IOL) implantation, using the 4-flanged IOL fixation technique, through a 2.4 mm corneal incision using a standard cartridge and injector, is presented. An IOL with 4 eyelets is used, through which a 6-0 polypropylene suture is threaded on one side and then loaded into a provided cartridge and inserted to the anterior chamber through a 2.4 mm corneal incision. Using the handshake technique, the suture ends are eventually threaded through the eyelets and secured outside the eye with the creation of 4 flanges. This technique was used in 6 eyes of 5 consecutive patients with the absence of capsular support. During all follow-up visits, the IOLs were well centered and stable, and the flanges were buried in the sclera and covered with the conjunctiva. No complications were recorded. This modification simplifies the technique and reduces the well-known complications of large corneal incisions.

POS-554 HEMODIALYSIS: CASE SERIES OF SIGNIFICANT THROMBOCYTOPENIA ASSOCIATED WITH DIALYZER CARTRIDGE SYSTEM

Thrombocytopenia, has been mentioned in recent case studies as common reaction during hemodialysis, could be associated with the dialyzer cartridge system. Here, the NxStage pre-attached dialyzer-cartridge used was CAR-172 cartridge express products, gamma-ray sterilized that includes an integrated dialyzer with biocompatible glycerin-free polyethersulfone membrane (PUREMA® H). NxStage system also has standard cartridge CAR-124 which allows replacement or connection for alternate dialyzers as per patients’ clinical requirement.

FEATURES OF MANUFACTURING TECHNOLOGY FOR THIN-WALLED PARTS

In Russia, there is a tendency to revive the machine tool industry. From here, research in the field of mechanical engineering technology becomes relevant. The most popular research in the field of mechanical engineering technology is research on improving the manufacturing technology of thin-walled parts based on more reliable calculations. Axisymmetric thin-walled parts are very widely used in mechanical engineering, and they can be divided into rings and shells depending on the ratio of length to diameter. The objects of research in the article, which is staged in the cycle of works, are rings. The review and analysis of devices for installing thin-walled parts and methods for calculating errors from the action of fixing forces and cutting forces showed that standard cartridges are most often used for installing rings, and in the calculations of fixing forces are assumed to be concentrated (applied at a point). The work offers special devices–mandrels with wide cams, which are advisable to use when installing rings in mass production. The rings have a tolerance for the diameter of the base hole, which is intended to be used in the study. The purpose of the study is to develop an engineering method for calculating the shape error in the cross section of a thin-walled ring fixed by three wide mandrel сams, taking into account the width of the contact area and the initial radial gap between the diameter of the workpiece hole and the diameter of the working cylindrical surface of the cam. The tasks that will allow you to achieve the goal, the initial data, and a number of assumptions to simplify the study are identified.

IQuant Auto: Automated Rapid Test Platform for Immunodiagnostics.

Point-of-care diagnostic devices aid in the early and rapid detection of immunological markers leading to better medical outcomes. Lateral flow immunoassays (LFIA) are fast assays that provide both qualitative and semi-quantitative results on site. Sample preparation for LFIA tests is usually done manually with multiple mixing steps and is prone to errors. The iQuant Auto is an entirely automated system that can handle sample preparation, effective transfer to lateral flow test membrane, and subsequent result estimation. The system uses a pneumatic system for fluid handling and sample preparation, and an image-based fluorescence reader for reaction visualization. The device works with test specific milli-fluidic lateral flow kit called iQPrep Kit, which has integrated reagent storage areas and valves for fluid control. The test kit can be manufactured using standard manufacturing techniques and can be produced at scale cheaply. The iQPrep Kit can be modified to test for various markers like HbA1c, Vitamin D, and TSH, while the hardware for sample preparation and the fluorescence reader remains the same. The device has a minimalist and intelligible graphical interface aiding smooth operation by less skilled people at resource-limited settings. Standard reference cartridges of different volume ratios were used to validate the functionality of the instrument. The intra- instrument coefficient of variation (CoV) of the mobile kit reader was found to be less than 0.62%. The positional accuracy of the system to ensure precise kit engagement with the other auxiliary systems was checked, and the CoV was 0.16%. The fluid handling capabilities were tested, and it was found that an average fluid loss of 10 µl results due to the liquid adherence to fluid channel walls and valve interfaces. The iQuant Auto is an easily operable, total analysis system for immunodiagnostics.

Cost-effective PEDOT:PSS Temperature Sensors Inkjetted on a Bendable Substrate by a Consumer Printer.

In this work, we report on a fabrication protocol to produce fully inkjet-printed temperature sensors on a bendable polyethylene terephthalate (PET) substrate. The sensing layer is made of polymer-based Poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) ink that is electrically contacted by an underlying interdigitated electrode (IDE) structure based on a silver nanoparticle (AgNP) ink. Both inks are available commercially, and no further ink processing is needed to print them using a cost-effective consumer printer with standard cartridges. The fabricated sensor modules are tested for different IDE dimensions and post-deposition treatments of the AgNP film for their response to a temperature range of 20 to 70 °C and moisture range of 20 to 90% RH (relative humidity). Attributed to the higher initial resistance, sensor modules with a larger electrode spacing of 200 µm show a higher thermal sensitivity that is increased by a factor of 1.8 to 2.2 when compared to sensor modules with a 150 µm-spacing. In all cases, the sensors exhibit high linearity towards temperature and a response comparable to state of the art.

Properties analysis of filtration materials with nanofibers addition

Nanofiber properties, methods of their production, and areas of their application have been presented. Parameters describing filtration materials with nanofibers addition were presented, and analyzed. Methodology for testing aerodynamic characteristics as well as characteristics of: efficiency, accuracy, and filter cartridges resistance with nanofibers addition, depending on the dust mass loading km were developed. Characteristic filtration parameters of the materials with nanofibers addition are presented. Five filtration inserts, differing in the filtration material with nanofibers addition, and without this layer were made. Test conditions were developed as well as a test stand was prepared. Aerodynamic characteristics tests of filter cartridges as well as filtration efficiency, accuracy, and flow resistance of standard (cellulose) cartridge, and the ones with nanofibers addition were performed. The positive effect of nanofiber layer on efficiency, and accuracy increase in the inlet engine air filtration was confirmed. Granulometric composition of air dust was assessed on a standard filter cartridge, and on a cartridge with nanofibers addition. Keywords: engine, air filter, nanofibers, filtration efficiency and accuracy, flow resistance, dust mass loading, grain size.

Binder Jetting of Si&lt;sub&gt;3&lt;/sub&gt;N&lt;sub&gt;4&lt;/sub&gt; Ceramics with Different Porosity

This article presents the results of the binder jetting technology application for the silicon nitride ceramics production. A modified version of the Plan-B 3D printer with an epoxy-based binder was used for silicon green bodies preforming. Silicon powder was pre-coated with epoxy resin, and the curing agent was added during 3-D printing of green bodies using a standard cartridge. Curing and removal of organics was carried out during the high-temperature vacuum drying of the printed preforms. Reaction-bonded silicon nitride was obtained by using pressureless sintering. An additional compaction of green bodies is proposed to reduce the porosity of green bodies and sintered ceramics. It is shown that the proposed methods allows to improve the mechanical properties of sintered specimens.

Silica-based chelating resin bearing dual 8-Hydroxyquinoline moieties and its applications for solid phase extraction of trace metals from seawater prior to their analysis by ICP-MS

Solid phase extraction (SPE) using chelating resins has been established as a convenient technique for samples pretreatment prior to trace metal analysis from complex matrices. Oxine chelating agents (e.g., 8-Hydroxyquinoline (8-HQ)) are popular moieties in the synthesis of chelating resins, due to their characteristic coordination chemistry. So far most of the reported silica-oxine chelators encompasses a single oxine molecule per spacer arm. In this work, two 8-HQ ligands have been covalently attached onto silica surface throughout a single linkage. The synthesized resin characterized with FTIR, elemental analysis and SEM. The main parameters affecting SPE procedures, such as pH, and sorption kinetics, investigated using batch experiments. The capacity exchange of the produced resin under optimized conditions was 0.219 and 0.161 mmol g−1 for Cu(II) and Mn(II) respectively. The resin packed into 10 ml standard cartridges and used with a typical SPE manifold for matrix removal prior to an ICP-MS analysis of transition metals (i.e., Cu, Cd, Ni, Pb, Zn, and Co) in seawater certified reference material samples and real samples from high saline seawater near the discharge zone of Yanbu desalination plant. The obtained results confirm the usefulness of the method.

An evaluation of the discriminating power of an Integrated Ballistics Identification System® Heritage™system with the NIST standard cartridge case (Standard Reference Material 2461)

Through analysis and comparison of firing pin, breech face, and ejector impressions, where appropriate, firearm examiners may connect a cartridge case to a suspect firearm with a certain likelihood in a criminal investigation. When a firearm is not present, an examiner may use the Integrated Ballistics Identification System (IBIS®), an automated search and retrieval system coupled with the National Integrated Ballistics Information Network (NIBIN), a database of images showing the markings on fired cartridge cases and bullets from crime scenes along with test fired firearms. For the purpose of measurement quality control of these IBIS® systems the National Institute of Standards and Technology (NIST) initiated the Standard Reference Material (SRM) 2460/2461 standard bullets and cartridge cases project. The aim of this study was to evaluate the overall performance of the IBIS® system by using NIST standard cartridge cases. By evaluating the resulting correlation scores, error rates, and percent recovery, both the variability between and within examiners when using IBIS®, in addition to any inter- and intra-variability between SRM cartridge cases was observed.

A Review of NIST Projects in Surface and Topography Metrology for Firearm Evidence Identification in Forensic Science

This is a review of the National Institute of Standards and Technology’s (NIST) efforts in surface metrology and topography measurements for firearm evidence identifications in forensic science. Based on the research projects in surface metrology and standardization, NIST researchers have developed Standard Reference Material (SRM) Bullets and Cartridge Cases (Certain commercial equipment, instruments, or materials are identified in this paper to specify adequately the experimental procedure. Such identification does not imply recommendation or endorsement by the National Institute of Standards and Technology, nor does it imply that the materials or equipment identified are necessarily the best available for the purpose) and established a 2D/3D Ballistics Topography Measurement System. They formulated a Traceability and Quality System to support nationwide ballistics identifications within the National Integrated Ballistics Information Network (NIBIN) in the United States. They have recently proposed a Congruent Matching Cells (CMC) method for accurate ballistic identification and error rate estimation, which provides a statistical foundation and a practical method to promote firearm evidence identifications from qualitative image comparisons to quantitative topography measurements.

Low within- and between-day variability in exposure to new insulin glargine 300 U/ml.

AimsTo characterize the variability in exposure and metabolic effect of insulin glargine 300 U/ml (Gla-300) at steady state in people with type 1 diabetes (T1DM).MethodsA total of 50 participants with T1DM underwent two 24-h euglycaemic clamps in steady-state conditions after six once-daily administrations of 0.4 U/kg Gla-300 in a double-blind, randomized, two-treatment, two-period, crossover clamp study. Participants were randomized to receive Gla-300 as a standard cartridge formulation in the first treatment period, and as a formulation with enhanced stability through polysorbate-20 addition in the second treatment period, or vice versa. This design allowed the assessment of bioequivalence between formulations and, subsequently, within- and between-day variability.ResultsThe cumulative exposure and effect of Gla-300 developed linearly over 24 h, and were evenly distributed across 6- and 12-h intervals. Diurnal fluctuation in exposure (within-day variability) was low; the peak-to-trough ratio of insulin concentration profiles was <2, and both the swing and peak-to-trough fluctuation were <1. Day-to-day reproducibility of exposure was high: the between-day within-subject coefficients of variation for total systemic exposure (area under the serum insulin glargine concentration time curve from time 0 to 24 h after dosing) and maximum insulin concentration were 17.4% [95% confidence interval (CI) 15–21] and 33.4% (95% CI 28–41), respectively. Reproducibility of the metabolic effect was lower than that of exposure.ConclusionsGla-300 provides predictable, evenly distributed 24-h coverage as a result of low fluctuation and high reproducibility in insulin exposure, and appears suitable for effective basal insulin use.

Applications of surface metrology in firearm identification

Surface metrology is commonly used to characterize functional engineering surfaces. The technologies developed offer opportunities to improve forensic toolmark identification. Toolmarks are created when a hard surface, the tool, comes into contact with a softer surface and causes plastic deformation. Toolmarks are commonly found on fired bullets and cartridge cases. Trained firearms examiners use these toolmarks to link an evidence bullet or cartridge case to a specific firearm, which can lead to a criminal conviction. Currently, identification is typically based on qualitative visual comparison by a trained examiner using a comparison microscope. In 2009, a report by the National Academies called this method into question. Amongst other issues, they questioned the objectivity of visual toolmark identification by firearms examiners. The National Academies recommended the development of objective toolmark identification criteria and confidence limits. The National Institute of Standards and Technology (NIST) have applied its experience in surface metrology to develop objective identification criteria, measurement methods, and reference artefacts for toolmark identification. NIST developed the Standard Reference Material SRM 2460 standard bullet and SRM 2461 standard cartridge case to facilitate quality control and traceability of identifications performed in crime laboratories. Objectivity is improved through measurement of surface topography and application of unambiguous surface similarity metrics, such as the maximum value (ACCFMAX) of the areal cross correlation function. Case studies were performed on consecutively manufactured tools, such as gun barrels and breech faces, to demonstrate that, even in this worst case scenario, all the tested tools imparted unique surface topographies that were identifiable. These studies provide scientific support for toolmark evidence admissibility in criminal court cases.

Usefulness of the INNOVANCE® PFA P2Y test cartridge for the detection of patients with congenital defects of the platelet P2Y12 receptor for adenosine diphosphate

The platelet function analyzer (PFA)-100 is used in clinical practice to screen patients with bleeding diathesis and suspected defects of primary hemostasis. A new cartridge, INNOVANCE PFA P2Y, has been specifically developed to monitor patients' response to drugs inhibiting the platelet P2Y₁₂ receptor for ADP. In this study, we compared the ability of INNOVANCE PFA P2Y to detect congenital defects of the platelet P2Y₁₂ receptor to that of standard cartridge formulations currently in clinical use. We studied two patients with severe P2Y₁₂ deficiency, one patient with heterozygous P2Y₁₂ deficiency and one with dysfunctional P2Y₁₂ receptor. Closure times were measured using 3 cartridges: collagen/ADP, collagen/epinephrine, and INNOVANCE PFA P2Y. The results obtained in the four patients with P2Y₁₂ defects were compared to those obtained for 20 healthy controls. In 2 patients with severe P2Y₁₂ deficiency, closure times of INNOVANCE PFA P2Y and collagen/ADP cartridges were >300 s, while those of collagen/epinephrine cartridge were variable (186s and >300 s). In the patient with dysfunctional P2Y₁₂, closure time of INNOVANCE PFA P2Y was >300 s, while closure times of collagen/ADP and collagen/epinephrine were normal. Closure times of all cartridges were normal in the patient with heterozygous P2Y₁₂ deficiency. Our study provides the first evidence that INNOVANCE PFA P2Y cartridge is sensitive to congenital severe and moderate defects of the platelet P2Y₁₂ receptors.

Synthesis of O-(2-[18F]fluoroethyl)-l-tyrosine based on a cartridge purification method

O-(2-[(18)F]fluoroethyl)-L-tyrosine (FET) is widely used as a positron emission tomography tracer for brain tumors. Usually, a high-performance liquid chromatography (HPLC) purification at the end of the two-step synthesis is applied. In this work, we report an automatic radiosynthesis of FET with a purification procedure based on standard cartridges. O-(2-[(18)F]fluoroethyl)-L-tyrosine was prepared by [(18)F]fluoroethylation of L-tyrosine by a two-step synthesis using a modified [(11)C]methionine module (Nuclear Interface). In the first reaction step, we synthesized [(18)F]fluoroethyltosylate starting from [(18)F]fluoride. After a purification step, L-tyrosine was [(18)F]fluoroethylated with [(18)F]fluoroethyltosylate. The final reaction mixture was purified by means of solid phase extraction. The FET was trapped on an SCX cartridge, eluted with saline solution and trapped again on an HRX cartridge. For a second purification step, the FET was eluted from the HRX cartridge with ammonium acetate buffer and collected on two SCX cartridges followed by a washing step with water. The final product was eluted with saline solution and neutralised with 450 μl NaHCO(3) solution (8.4%). The synthesis was finished after 50 min and delivered the FET in a range of 3-16 GBq. The synthesis typically yielded 41% (21 experiments) of FET (d.c.) without an HPLC purification step. The radiochemical purity ranged between 97% and 100%. We present a radiosynthesis of FET where the usually used HPLC purification procedure has been substituted by a purification step based on standard cartridges. This method is useful for automatic modules without an expensive HPLC purification unit and for the routine production of FET.

Design and manufacture of surface textures on gun cartridge cases to trap DNA material

US and Australian work has shown that the effectiveness of extracting deoxyribonucleic acid (DNA) from standard gun cartridges is low and so analysis costs are high ( www.cci.gov/Reference/LpDNACtg_files ). The presence of greater than 1 ng of trapped bio-material would increase the success rates of DNA profiling and facilitate cheaper DNA analysis. The aim of this work is to increase the amount of recoverable DNA from a gun user deposited on fired cartridges, using microtextured surfaces as DNA receptors. Success would increase the probability of identifying perpetrators of gun crime through DNA matching. Various textures have been applied to flat surfaces of cartridge case material and the effects of those surface textures on trapping skin materials have been evaluated. In addition to treated/patterned surfaces, standard emery abrasive paper was adopted as a control medium. From the different surfaces tested, the emery abrasive paper was found to be most effective at trapping skin debris. Rough surfaces with pyramid textures, which are similar to features on emery paper, were subsequently manufactured on cartridge rims by a standard knurling process. Scratch tests were carried out to simulate the process of handling and loading these cartridges during the use of firearms. DNA test results of the knurled cartridges after firing, showed a high success rate of DNA profiling and high matching percentage to the donor's DNA profile.

An Iterative Image Registration Algorithm by Optimizing Similarity Measurement.

A new registration algorithm based on Newton-Raphson iteration is proposed to align images with rigid body transformation. A set of transformation parameters consisting of translation in x and y and rotation angle around z is calculated by optimizing a specified similarity metric using the Newton-Raphson method. This algorithm has been tested by registering and correlating pairs of topography measurements of nominally identical NIST Standard Reference Material (SRM 2461) standard cartridge cases, and very good registration accuracy has been obtained.

Preparation and evaluation of a lubricious treated cartridge used for implantation of intraocular lenses

In the last decades, many surface modification technologies have been developed in an attempt to improve the function of medical device surfaces by adding or enhancing surface characteristics. These value-added processes included treatment to affect lubricity, hemocompatibility and drug delivery. A unique hydrophilic, lubricious coating was developed to treat hydrophobic polymer surfaces. The coating platforms described are composed of a polyelectrolyte molecular film containing hydrophilic, lubricant molecules. The molecular film is then further cross-linked with di-functional aldehyde molecules to form an interpenetrating network (IPN). The IPN entraps lubricant molecules in the matrix and provides for prolonged stability of the lubricity. This coating was applied to cartridges which were used to deliver intraocular lenses (IOLs) that replaced the cataractous crystalline lenses in patients In order to determine the safety and effectiveness of the coating, a rabbit in vivo study was designed to evaluate the ease of implantation and postoperative response to implantation of the foldable acrylic IOLs. The performance evaluation of the lubricious treated cartridges focused on the ease of insertion and post-IOL implantation response. It was found that the UNFOLDER™ Emerald Insertion System (Advanced Medical Optics) with lubricious treated cartridges generally required lower insertion forces than the standard UNFOLDER™ Emerald cartridges. The postoperative inflammatory response following lens extraction and posterior chamber implantation of low (6D), medium (20D) and high (30D) diopter foldable acrylic IOLs with both treated and standard cartridges was mild. Inflammation generally resolved by 3 weeks. Thus, in this animal study, the coating was shown to be effective in assisting the delivery of IOLs through cartridges, without causing any adverse effects.