Method to determine particle release during long-term loading for assessment of coating durability of cardiovascular stents

Many catheters and vascular implants are coated to increase biocompatibility or to reduce friction during catheter based implantation. Several regulations require assessment of coating durability over the implant’s life time. An in vitro method for stent testing is presented to measure released particulate matter at defined inspection intervals. The method was validated using polystyrene microspheres with a size of 10, 25 and 50 μm to check for particle recovery (n=6). Two cleaning steps followed. Particle counting was performed by light obscuration method. The recovery rate was 103±5% (10μm), 94±4% (25 μm) and 78±12% (50 μm), respectively, meeting the requirements of FDA guidance documents (i.e. FDA 1545). Less than 3% of the particles were found in the cleaning solutions. The method using a fixed volume during stent loading can be adapted to all durability testers where tubes are used to fix the stents (radial pulsatile, bending, axial compression, torsion).

Modification and validation of the test procedure for determination of sub-visible particulate matter in parenteral solutions, using the Coulter method

The State Pharmacopoeia of the Russian Federation, 14th edition provides for determination of sub-visible particles (less than 100 µm in size) in parenteral dosage forms using the Coulter method, in addition to the light obscuration particle count test and microscopy. However, the proposed 100 µm aperture tube does not enable assessment of the whole range of sub-visible particle sizes. Therefore, research is needed to find optimal test conditions for determination of sub-visible particulate matter by the Coulter method. The aim of the study: modification of the Coulter-based procedure using a 200 µm aperture tube, and performance of validation studies. Materials and methods: Multisizer 4e Coulter counter, suspensions of reference latex particles (10 µm, 20 µm, and 43 µm), and a particulate count reference standard containing 0.998 × 106 particles/mL were used in the study. The following parameters were assessed during validation: accuracy, repeatability, linearity. Results: the study confirmed the feasibility of using the modified Coulter-based procedure with a 200 µm aperture tube. The following values were obtained during validation of the modified test procedure: accuracy was 5.3% (deviation from the mean value) as compared to the particulate count reference standard, and 4.2% as compared to the light obscuration method. Repeatability was 1% (relative standard deviation) for the particle concentration of approximately 10000 per 1 mL, and 7.6% for the particle concentration of approximately 300 per 1 mL. The study demonstrated the linearity of the procedure, the linear correlation coefficient was more than 0.99. Conclusions: the studied validation parameters of the modified test procedure were shown to comply with the acceptance criteria. The modified test procedure will enable assessment of the whole range of sub-visible particle sizes when testing parenteral solutions for particulate contamination: sub-visible particles.

Multi-Wavelength Densitometer for Experimental Research on the Optical Characteristics of Smoke Layers

A novel multi-wavelength densitometer was built for the purpose of continuous and simultaneous measurements of light obscuration in smoke layers, concurrently in five bands (λ = 450 nm, 520 nm, 658 nm, 830 nm and 980 nm). This device was used for determining transmittance and visibility in smoke parameters of a smoke layer from the fire of 1.00 dm3 of n-Heptane in a 0.33 × 0.33 m tray located in a test chamber (9.60 × 9.80 × 4.00 m3). The performance of the device was compared with a commercial Lorenz densitometer at 880 nm. Significant differences in measured value of transmittance were observed between the different sensors – from 65% at 450 nm (blue light), 80% at 658 nm (red light) to 95% at 980 nm (IR). The visibility in smoke, estimated following the theory of Jin for light reflecting signs (K = 3), ranged from 7.5 m (blue light) to 12 m (red light) and for the light-emitting (K = 8) signs from 18 to 32 m, respectively. The performed experiment has confirmed the applicability and added value of multi-wavelength measurements of light-extinction in fire experiments. The device was sensitive to temperature variations and requires active cooling and careful warm-up prior to experiments, to reach the expected sensitivity.

Compatibility of medications with intravenous lipid emulsions: Effects of simulated Y-site mixing

Purpose To determine the physical intravenous Y-site compatibility of 19 commonly used medications at pediatric concentrations with 3 different types of lipid emulsion. Methods Medications at commonly used pediatric concentrations were mixed in a 1:1 ratio with lipid emulsions (Intralipid, Nutrilipid, and Smoflipid) and incubated at room temperature for 4 hours to simulate Y-site administration. Each sample was then diluted with particle-free water and analyzed using the analytical technique of light obscuration recommended in United States Pharmacopeia (USP) general information chapter 729 (USP <729>). Physical compatibility was determined by measuring the percentage of fat residing in globules larger than 5 µm (PFAT5) per USP <729> recommendations. Results Most combinations tested were physically compatible based on USP <729> regulations. Incompatibilities differed for the different brands of lipid emulsion. The two combinations that met USP <729> criteria for physical incompatibility were cisatracurium 2 mg/mL with Intralipid and gentamicin 2 mg/mL with Smoflipid. Conclusion Three different lipid emulsions were physically compatible at the Y site with the majority of medications tested. Data regarding Y-site compatibility for one lipid emulsion product cannot be safely extrapolated to another without additional testing.

Optimization of online particle counting with a 3D-printed bubble trap

Particulate evaluation is needed for the approval of cardiovascular devices. Air bubbles lead to higher particle counts when light obscuration method (LOM) is used. The aim of the study was to test a custom made bubble trap that removes air bubbles (2 - 100 μm) from a flow circuit prior to online particle counting. Artificially generated air bubbles were counted with an online particle counter with and without the bubble trap. Air bubbles were reduced by about 71 % to 91 % by using the bubble trap.

Measurements of Optical Properties of Smoke Particulates Produced from Burning Polymers and Their Implications

A series of cone calorimetry experiments and simultaneous gravimetric sampling and light extinction (GSLE) measurements were performed to determine the optical properties (light obscuration and extinction characteristics) of smoke particulates produced from burning polymers. The polymer selected in the present study was acrylonitrile-butadiene styrene (ABS), which has a moderate smoke yield during combustion, and unplasticized polyvinyl chloride (UPVC), which has a lower smoke yield than ABS. The experiments show that the measured light obscuration for UPVC smoke particles is much lower than that for ABS smoke particles because of the low rate of smoke production during combustion. Results from the simultaneous GSLE measurements demonstrate more clearly that UPVC smoke particles represent a lower efficiency of light obscuration on a per-unit smoke mass basis, resulting in a 41.3% reduction in a mass specific extinction coefficient compared to the ABS smoke particles. Numerical analysis was performed to further elucidate the effect of optical properties on the smoke behavior using the Fire Dynamics Simulator (FDS) (Version 6.7.1, National Institute of Standards and Technology (NIST), Gaithersburg, MD, USA). The numerical results clearly demonstrated that the UPVC combustion, with its relatively low heat release rate and mass specific extinction coefficient, caused a significant delay in detecting a fire with a smoke detector compared to ABS combustion.