Elastomeric Respirators for COVID-19 and the Next Respiratory Virus Pandemic: Essential Design Elements.

Respiratory viruses are transmitted via respiratory particles that are emitted when people breath, speak, cough, or sneeze. These particles span the size spectrum from visible droplets to airborne particles of hundreds of nanometers. Barrier face coverings ("cloth masks") and surgical masks are loose-fitting and provide limited protection from airborne particles since air passes around the edges of the mask as well as through the filtering material. Respirators, which fit tightly to the face, provide more effective respiratory protection. Although healthcare workers have relied primarily on disposable filtering facepiece respirators (such as N95) during the COVID-19 pandemic, reusable elastomeric respirators have significant potential advantages for the COVID-19 and future respiratory virus pandemics. However, currently available elastomeric respirators were not designed primarily for healthcare or pandemic use and require further development to improve their suitability for this application. The authors believe that the development, implementation, and stockpiling of improved elastomeric respirators should be an international public health priority.

Ceftolozane-tazobactam in an elastomeric infusion device for ambulatory care: an in vitro stability study.

Objectives: Published in vitro stability data for ceftolozane-tazobactam supports intermittent short duration infusions. This method of delivery is not feasible for many outpatient antimicrobial therapy services that provide only one or two visits per day. This study aimed to assess time, temperature and concentration-dependent stability of ceftolozane-tazobactam in an elastomeric infusion device for continuous infusion across clinically relevant ranges encountered in outpatient antimicrobial therapy. Methods: Ceftolozane-tazobactam was prepared to achieve initial concentrations representing total daily doses for 'renal', 'standard' and 'high' dose schedules in elastomeric infusion devices with a volume of 240 mL. Infusion devices incubated at room and body temperature were serially sampled over 48 hours. Refrigerated infusion devices were sampled over 10 days. Concentrations of ceftolozane and tazobactam were separately quantified using a validated ultra-high performance liquid chromatography-photodiode array method. Results: The greatest loss of ceftolozane occurred at 37°C, however, stability remained above 90% at 24 hours. Tazobactam was more stable than ceftolozane under these conditions. There was minimal loss at 4°C for either component over 7 days. Conclusions: Ceftolozane-tazobactam is suitable for ambulatory care delivered as a continuous infusion via an elastomeric infusion device.

Assessment of the stability of citrate-buffered flucloxacillin for injection when stored in two commercially available ambulatory elastomeric devices: INfusor LV (Baxter) and Accufuser (Woo Young Medical): a study compliant with the NHS Yellow Cover Document (YCD) requirements.

Objectives: To investigate the effect of pH and buffers on the degradation rate of flucloxacillin and to determine if flucloxacillin can be stabilised using a buffered diluent for up to 14 days when stored at 2°C-8°C including a 24-hour infusion period at 32°C in two elastomeric devices (Accufuser and INfusor LV) filled to 240 mL. Testing as per the NHS Pharmaceutical Quality Assurance Committee Yellow Cover Document (YCD) requirements. Methods: A validated stability indicating high-performance liquid chromatography method was used for assessing the stability of flucloxacillin diluted in 0.3% w/v citrate-buffered saline pH 7.0 when stored at 2°C-8°C in two ambulatory devices (Accufuser and INfusor LV). Flucloxacillin at 10 and 50 mg/mL diluted in 0.3% w/v citrate-buffered saline pH 7.0 to a final volume of 240 mL and stored at 2°C-8°C, including 24 hours at 32°C, was tested from two batches in replicate (n=3) at five time points for up to 14 days according to the requirements of the YCD. Results: Greater than 95% of the zero-time concentration of flucloxacillin at 10 and 50 mg/mL remained when stored at 2°C-8°C after 14 days including 24 hours at 32°C in both Accufuser and INfusor LV devices. Conclusions: Flucloxacillin sodium stability was improved, and complied with UK national standards, by using a diluent of 0.3% w/v citrate-buffered saline pH 7 in both Accufuser and INfusor LV ambulatory devices when filled to 240 mL. The data support assigning a shelf-life of up to 14 days (13 days stored at 2°C-8°C and 24 hours at 32°C). Flucloxacillin may now be used appropriately as a continuous 24-hour infusion in outpatient parenteral antimicrobial therapy services, providing further opportunity to avoid or shorten patient hospital stays, as well as support ideal antimicrobial stewardship principles.

Quantifying the Vial Capping Process: Residual Seal Force and Container Closure Integrity.

Capping completes the closure of parenteral drug products in the final packaging container and is critical in maintaining an integral seal to ensure product quality. Residual seal force (RSF) is considered the sole quantifiable attribute for measuring seal "goodness" and potentially enables nonsubjective, consistent setting of cappers across manufacturing sites. However, the consistency and reliability of RSF measurement and data have been scarcely reported, and the relationship between RSF and container closure integrity (CCI) remains poorly understood.Here, we present a large data set generated from a commercial capper and the results from a laboratory capper of glass vials and rubber stoppers with aluminum caps. All RSF values exhibited significant variability. We evaluated four potential sources of variability: the capper, the RSF tester, the time-dependent nature of RSF, and the components. We determined that the capper, the tester, and the time-dependent nature are not main sources. Dimensional tolerances of the packaging components were the root cause for the container closure system (CCS) configurations tested in this study.This study correlated RSF with CCI (via helium leakage), although CCI is not sensitive to RSF; CCI was maintained even for loosely capped vials with no measurable RSF. This was attributed to the stopper's two sealing surfaces: the valve seal and the land seal. A methodology capable of differentiating the two seals' functions demonstrated that vials with only the valve seal always passed leakage testing for a selected CCS configuration in this study, while vials with only the land seal failed CCI at low RSF values. This observation allows proposal of a low RSF limit that is safe even when the valve seal is defective. Simplified statistical analysis of commercial capping data, with the input of sample size, allowed the relationship between RSF's low limit and an allowable failing rate to be established. Overall, despite the inherent variability of RSF, this study shows that it is a feasible parameter for capping process quantification and demonstrates the potential of RSF measurement in capper setup.LAY ABSTRACT: Pharmaceutical vials are typically closed off with an elastomeric stopper that is secured onto the vial with an aluminum crimp cap (or seal) such that the entire assembly is meant to protect the vial's contents from external contamination. Therefore, the capping process is critical for ensuring container closure integrity. Characterizing the effectiveness of a seal in a nonsubjective and quantifiable manner is challenging. In this communication, we report the evaluation of residual seal force measurements (the compression force that the crimp cap exerts on the stopper) to evaluate capping for a large set of samples generated on both an at-scale commercial capper and a benchtop laboratory capper. We propose a test methodology, based on a statistical approach, for establishing permissible lower residual force limits that would provide a high degree of confidence to the capping process. This is a useful tool for consistent capper setup and capping process quantification.

Comparison of a Lyophilized Drug Product to Other Solid and Liquid Media for the Extraction of Elastomeric Oligomers from a Butyl Rubber Stopper.

Lyophilization is commonly used to extend the shelf life of pharmaceutical products that are otherwise unstable when stored as a liquid formulation. However, the ability of a lyophilized drug, or other solid medium, to leach or extract substances from a pharmaceutical packaging material is not well characterized. To provide insight into this area of uncertainty, the extraction properties of a lyophilized drug product, the lyophilized drug product reconstituted in water, and several other solid and liquid media of varying polarity were determined using a glass vial with a butyl rubber stopper as a representative pharmaceutical packaging system. The results obtained in this study show that the extracting power of a medium, whether solid or liquid, was primarily a function of polarity. Thus, the amount of each extractable observed for the lyophilized and reconstituted drug product were in trend with the other solid and liquid media, respectively. Nevertheless, it was notable that the lyophilized drug product was able to leach substances from the stopper in quantifiable amounts, whereas the reconstituted drug product contained no detectable leachables. Using a mathematical relationship, it was determined that the extraction power of the lyophilized drug product was equivalent to a 50/50 isopropanol/water solution.LAY ABSTRACT: Freeze drying is commonly used to extend the shelf life of pharmaceutical products that are otherwise unstable when stored as a liquid formulation. However, the propensity for substances to migrate from a pharmaceutical packaging material and into a solid drug formulation is not well characterized. To provide insight into this area of uncertainty, the migration of substances from a glass vial with a butyl rubber stopper and into a lyophilized drug product, the drug product reconstituted with water, as well as several solid and liquid media of varying polarity were assessed. The results obtained in this study show that the extracting power of a medium, whether solid or liquid, was primarily a function of polarity and thus could be related to one another. Furthermore, the results for the freeze-dried and reconstituted drug products were in trend with the other solid and liquid media tested, respectively, and showed that the freeze-dried drug was able to leach substances from the stopper in measureable amounts, whereas the reconstituted drug product contained no substances that had originated from the stopper.

Temperature profiles of antibiotic-containing elastomeric infusion devices used by ambulatory care patients.

PURPOSE: The temperature profiles of antibiotic-containing elastomeric infusion devices used by ambulatory care patients under various environmental conditions were evaluated. METHODS: A prospective, descriptive survey of temperature exposure was conducted in 4 publically funded hospitals. Over a 12-month period, electronic temperature-recording devices were attached to the antibiotic infusion devices (infusers) of prospectively randomized hospital-in-the-home (HITH) participants. Temperatures were recorded immediately after infuser connection and every 5 minutes thereafter for 24 hours. A structured data collection form was used to collect information on basic clinical and demographic characteristics and aspects of daily living (i.e., how and where the infuser was carried during the day, times the participant went to and arose from bed, location of the infuser while sleeping, and dates and times the infuser was connected and disconnected). RESULTS: A total of 115 patients successfully completed the study (17-91 years old, 55% males). A total of 31,298 temperature readings were collected. The storage location of the infuser did not influence daytime readings. However, the overnight storage location did have a significant impact on the temperatures recorded overnight. The mean temperatures of infusers stored on the bed or on the body overnight were significantly higher than those for infusers stored away from the bed. Diurnal and seasonal influences were also detected. Significantly warmer temperatures were recorded in afternoons and evenings and during the summer months. CONCLUSION: Antibiotics administered to HITH patients via continuous infusion were frequently exposed to temperatures in excess of 25 °C. Specific patient behaviors and seasonal and chronological factors influenced temperatures. The findings challenge the validity of current fixed-temperature models for testing stability, which do not reflect conditions found in clinical practice.

A Transparent, Highly Stretchable, Autonomous Self-Healing Poly(dimethyl siloxane) Elastomer.

An innovative self-healing polydimethylsiloxane (PDMS) elastomer, namely, PDMS-TFB, is reported by incorporating the reversibly dynamic imine bond as the self-healing points into the PDMS networks. The PDMS-TFB elastomer features good optical transmittance (80%) in full visible light region, high stretchability (≈700%), and excellent autonomous self-healing ability at room temperature. Surprisingly, the self-healing behavior can take place in water and even at a temperature as low as -20 °C in air, showing a promising outlook for broader applications. As a proof-of-concept, this study demonstrates the use of the PDMS-TFB elastomer for preparing anticorrosion coating and adhesive layer, and also the use of such an elastomer to be the platform for fabricating the flexible interconnector and chemical sensor. Remarkably, no significant difference is observed between the pristine and healed samples. Taking full advantage of these unique properties, it is anticipated that such a PDMS-TFB elastomer shows wide applications in the fields of materials science, electronics, biology, optics, etc.

Avaliação da intensidade das forças liberadas por ligaduras elásticas de diferentes cores / Evaluation of intensity of forces liberated by different colour elastic ligatures

Foi avaliada a intensidade das forças liberadas por ligaduras elásticas de cinco cores quando imersas em solução de saliva artificial. As amostras foram testadas por meio de uma máquina de ensaios de tração, nos períodos de tempo inicial, 1 dia, 7, 14, 21 e 28 dias de imersão em saliva artificial. Encontrou-se uma diminuição acentuada e estatisticamente significante nas forças liberadas para as primeiras 24 horas (P<0,0001), sendo que entre os demais períodos (7, 14, 21, 28 dias) ocorreu uma queda gradativa não significante destes valores. Entretanto, não houve diferença significante para as magnitudes de forças liberadas pelas ligaduras elásticas modulares em relação às diferentes cores analisadas

Thermoplastic elastomers in medical applications.

TPEs provide medical designers with a broad spectrum of soft-feel, hygienic materials that can readily fulfill accepted medical industry standards with the exception of body implants. Ultimate performance is a combination of tailor-made formulations coupled with innovative design that captures the capability of the material's properties and thermoplastic processing techniques, including combination with other polymers by coinjection moulding or coextrusion.

Utilization of an elastomeric continuous infusion device to maintain catheter patency.

The frequency of vascular access device (VAD) complications increases with the complexity of therapy or poor catheter maintenance. Catheter occlusions are most frequently caused by inadequate catheter flushing or technique. The study group of 25 patients was placed on an elastomeric continuous infusion device with patient costs and occlusion rates compared with historic data. The use of the elastomeric continuous infusion device saved an average of $123 per week when compared with traditional flushing devices, which cost from $216 to $248 per week. The incidence of catheter patency loss was reduced by 50%. The nurses also reported considerable timesaving in catheter maintenance and patient education and an overwhelmingly positive response from staff and patients.