Physicochemical stability of bortezomib solutions for subcutaneous administration.

For the majority of cytotoxic drug preparations, such as bortezomib, the unit dose information is not available. In addition, there is a lack of information on the physicochemical stability of the pharmaceutical preparation after opening; this information is crucial for its administration to patients in successive visits, and the per-patient cost can be affected. The purpose of our proposed physicochemical stability study is to determine the shelf life of the reconstituted liquid product under refrigeration and clinical practice conditions. This evaluation was extended to both vials and ready-to-use syringes prefilled with the contents of the open vial. The stability test design includes the specified storage conditions and the critical physicochemical parameters of reconstituted injectable bortezomib. Furthermore, this approach includes the determination of impurities, the monitoring of the purity of the mean peak using a photodiode array, the control of the mass balance, the monitoring of subvisible particles using a laser diffraction analyser, and the setting of stability specifications. For the chemical stability study, the amount of bortezomib and its degradation products were determined using a stability-indicating HPLC method. The physical inspection of the samples was performed throughout the stability study, and their pH values were also monitored. Bortezomib (2.5 mg/mL) in 0.9% sodium chloride remained stable for 7 days when stored in both polypropylene syringes and vials at 5 ± 3 °C (refrigeration) and shielded from light. Additionally, it exhibits stability for 24 h under storage conditions simulating clinical use (20-30 °C and protected from light). The proposed protocol provides the stability in the vials once reconstituted and in prefilled refrigerated syringes; this protocol can be used to reduce waste and increase cost savings.

Non-destructive Raman Method Development for Quantifying Active Pharmaceutical Ingredient in an Oral Suspension Through Plastic Dosing Syringes.

For liquid drug products, e.g., solutions or suspensions for oral or parenteral dosing, stability needs to be demonstrated in primary packaging during storage and in dosing devices during in-use periods per quality guidelines from the International Conference on Harmonisation (ICH) and the European Agency for the Evaluation of Medicinal Products (EMEA). One aspect of stability testing for liquid drug products is in-use stability, which typically includes transferring the liquid samples into another container for further sample preparation with extraction diluent and necessary agitation. Samples are then analyzed with traditional chromatography methods, which are laborious, prone to human errors, and time-consuming, especially when this process needs to be repeated multiple times during storage and in-use periods. Being able to analyze the liquid samples non-destructively would significantly improve testing efficiency. We investigated different Raman techniques, including transmission Raman (TRS) and back scatter Raman with a non-contact optic (NCO) probe, as alternative non-destructive tools to the UHPLC method for API quantitation in in-use liquid samples pulled into plastic dosing syringes. The linearity of the chemometric methods for these two techniques was demonstrated by cross-validation sample sets at three levels over an API concentration range of 60 to 80 mg/mL. The accuracy of the chemometric models was demonstrated by the accurate prediction of the API concentrations in independent samples from four different pilot plant batches manufactured at different sites. Both techniques were successful in measuring a signal through a plastic oral dosing syringe, and predicting the suspension API concentration to within 4% of the UHPLC-measured value. For future work, there are opportunities to improve the methodology by exploring additional probes or to expand the range of applications by using different sample presentations (such as prefilled syringes) or formulation matrices for solutions and suspensions.

Effect of gutta-percha solvents on the push-out bond strength to root dentin of a syringe-mixed resin sealer and premixed bioceramic sealer.

PURPOSE: To assess the push out bond strength (POBS) of a syringe-mixed resin sealer and a premixed bioceramic sealer to root dentin exposed to different gutta-percha (GP) solvents and to determine the mode of failure. METHODS: A total of 200 horizontal root slices (1 mm thickness) were prepared up to size 40, 0.04 taper and randomly divided into four main groups based on solvent (Endosolv, orange oil, chloroform) and control (saline), then subdivided into two subgroups based on sealer type (AH Plus Jet and iRoot SP). Samples were exposed to respective solvents for 5 minutes and after the final rinsing, canal spaces were filled with either AH Plus Jet or iRoot SP. POBS test was performed 2 weeks after incubation and mode of failure following POBS test was evaluated. Data were analyzed using two-way ANOVA and Dunnett post hoc analysis (P< 0.05). Failure mode patterns were categorized as adhesive, cohesive and mixed failures. RESULTS: There was no significant difference (P> 0.05) in POBS between all solvent groups against the control in both AH Plus Jet and iRoot SP groups. Regardless of the use of solvents, AH Plus Jet group had significantly higher bond strength (P< 0.001) compared to iRoot SP group. The predominant mode of failure was mixed failure in all groups irrespective of type of sealer and exposure to solvents. CLINICAL SIGNIFICANCE: This study showed that exposure to gutta-percha solvents (chloroform, orange oil and Endosolv) for 5 minutes did not affect the bond strengths of both iRoot SP (bioceramic sealer) and AH Plus (resin sealer) to root dentin.

Community Pharmacy Needle Exchange Programme: What Can Analysis of the Data Tell Us about the Changing Drug Market in Ireland?

Community Pharmacy Needle Exchanges are a harm reduction measure that have been established in a number of countries to provide access to sterile injecting equipment for people who inject drugs (PWID). To ensure that they are meeting needs, it is important to monitor the use of the services. This study aimed to determine patterns of needle distribution and return in community pharmacies in Ireland over time. The number of pharmacies, needle packs, clean needles and returned packs was obtained from the Health Service Executive (HSE) Planning and Business Information Unit (PBI). Yearly totals were calculated to show patterns from 2015 to 2022. There has been an 18% decline in the number of pharmacies providing the service since 2015, with a 19% decline in the number of packs provided and a 21% decline in the number of packs returned. The proportion of packs returned was 23% in 2015 and 18% in 2022. There has been a 16% decline in the number of sterile needles provided and a 6% reduction in the average number of needles per individual since 2017. Declining needle use and low rates of used needle return (against a backdrop of large numbers of PWID that have not significantly reduced over time) suggest that there is a need to investigate if community pharmacies in Ireland have the scope to improve their harm reduction impact. This raises questions in terms of the need to both improve and adapt the service against a backdrop of changing drug markets. Key recommendations include the need to review the harm reduction services employed by participating pharmacies when providing new equipment and organising the return of used equipment.

Were Needles Everywhere?: Differing Views on Syringe Waste and Disposal Associated With Needs-Based Syringe Services Programs Among Community Partners and Persons Who Inject Drugs.

BACKGROUND: Community concerns surrounding syringe waste are a common barrier to syringe services program (SSP) implementation. In Kanawha County, West Virginia, community opposition to SSPs resulted in the closure of needs-based SSPs prior to and during an HIV outbreak among persons who inject drugs (PWID). This qualitative analysis examines views of PWID and community partners on syringe waste and disposal associated with needs-based SSPs. METHODS: Qualitative interviews with 26 PWID and 45 community partners (medical and social service providers, law enforcement personnel, policymakers, and religious leaders) were conducted. Interviews were recorded, transcribed, and coded. Code summaries described participants' views on syringe waste and disposal and needs-based SSPs. RESULTS: Community partners and PWID who favored needs-based SSPs reported that needs-based SSPs had not affected or reduced syringe waste. Conversely, community partners who favored one-to-one exchange models and/or barcoded syringes described needs-based SSPs increasing syringe waste. Community partners often cited pervasive community beliefs that SSPs increased syringe waste, risk of needlesticks, drug use, and crime. Community partners were unsure how to address syringe waste concerns and emphasized that contradictory views on syringe waste posed barriers to discussing and implementing SSPs. CONCLUSIONS: Participants' views on whether syringe waste was associated with needs-based SSPs often aligned with their support or opposition for needs-based SSPs. These differing views resulted in challenges finding common ground to discuss SSP operations amid an HIV outbreak among PWID. SSPs might consider addressing syringe waste concerns by expanding syringe disposal efforts and implementing community engagement and stigma reduction activities.

Effects of colour-coded compartmentalised syringe trays on anaesthetic drug error detection under cognitive load.

BACKGROUND: Anaesthetic drug administration is complex, and typical clinical environments can entail significant cognitive load. Colour-coded anaesthetic drug trays have shown promising results for error identification and reducing cognitive load. METHODS: We used experimental psychology methods to test the potential benefits of colour-coded compartmentalised trays compared with conventional trays in a simulated visual search task. Effects of cognitive load were also explored through an accompanying working memory-based task. We hypothesised that colour-coded compartmentalised trays would improve drug-detection error, reduce search time, and reduce cognitive load. This comprised a cognitive load memory task presented alongside a visual search task to detect drug errors. RESULTS: All 53 participants completed 36 trials, which were counterbalanced across the two tray types and 18 different vignettes. There were 16 error-present and 20 error-absent trials, with 18 trials presented for each preloaded tray type. Syringe errors were detected more often in the colour-coded trays than in the conventional trays (91% vs 83%, respectively; P=0.006). In signal detection analysis, colour-coded trays resulted in more sensitivity to the error signal (2.28 vs 1.50, respectively; P<0.001). Confidence in response accuracy correlated more strongly with task performance for the colour-coded tray condition, indicating improved metacognitive sensitivity to task performance (r=0.696 vs r=0.447). CONCLUSIONS: Colour coding and compartmentalisation enhanced visual search efficacy of drug trays. This is further evidence that introducing standardised colour-coded trays into operating theatres and procedural suites would add an additional layer of safety for anaesthetic procedures.

Advancing injection force modeling and viscosity-dependent injectability evaluation for prefilled syringes.

The development of PFS requires a detailed understanding of the forces occurring during the drug administration process and patient's capability. This research describes an advanced mathematic injection force model that consisting hydrodynamic force and friction force. The hydrodynamic force follows the basic law of Hagen-Poiseuille but refines the modeling approach by delving into specific properties of drug viscosity (Newtonian and Shear-thinning) and syringe shape constant, while the friction force was accounted from empty barrel injection force. Additionally, we take actual temperature of injection into consideration, providing more accurate predication. The results show that the derivation of the needle dimension constant and the rheological behavior of the protein solutions are critical parameters. Also, the counter pressure generated by the tissue has been considered in actual administration to address the issue of the inaccuracies of current injection force evaluation preformed in air, especially when the viscosity of the injected drug solution is below 9.0 cP (injecting with 1 mL L PFS staked with 29G ½ inch needle). Human factor studies on patients' capability against medication viscosity filled the gap in design space of PFS drug product and available viscosity data in very early phase.

Come back when you're infected: pharmacy access to sterile syringes in an Arizona Secret Shopper Study, 2023.

BACKGROUND: Pharmacies are critical healthcare partners in community efforts to eliminate bloodborne illnesses. Pharmacy sale of sterile syringes is central to this effort. METHODS: A mixed methods "secret shopper" syringe purchase study was conducted in the fall of 2022 with 38 community pharmacies in Maricopa and Pima Counties, Arizona. Pharmacies were geomapped to within 2 miles of areas identified as having a potentially high volume of illicit drug commerce. Daytime venue sampling was used whereby separate investigators with lived/living drug use experience attempted to purchase syringes without a prescription. Investigator response when prompted for purchase rationale was "to protect myself from HIV and hepatitis C." A 24-item instrument measured sales outcome, pharmacy staff interaction (hostile/neutral/friendly), and the buyer's subjective experience. RESULTS: Only 24.6% (n = 28) of 114 purchase attempts across the 38 pharmacies resulted in syringe sale. Less than one quarter (21.1%) of pharmacies always sold, while 44.7% never sold. Independent and food store pharmacies tended not to sell syringes. There emerged distinct pharmacy staff interactions characterized by body language, customer query, normalization or othering response, response to purchase request and closure. Pharmacy discretion and pharmacy policy not to sell syringes without a prescription limited sterile syringe access. Investigators reported frequent and adverse emotional impact due to pharmacy staff negative and stigmatizing interactions. CONCLUSIONS: Pharmacies miss opportunities to advance efforts to eliminate bloodborne infections by stringent no-sale policy and discretion about syringe sale. State regulatory policy facilitating pharmacy syringe sales, limiting pharmacist discretion for syringe sales, and targeting pharmacy-staff level education may help advance the achievement of public health goals to eliminate bloodborne infections in Arizona.

Seringas utilizadas na vacinação da capital | #VacinaSampa

Três tipos de seringas são utilizadas para aplicar a vacina da Covid-19 e uma delas possui um dispositivo de segurança que pode te confundir no momento da aplicação. Entenda melhor no vídeo!

Container-content interactions with radiopharmaceuticals: Seeing is believing.

This perspective article addresses the critical issue of container-content interactions in the administration of intravenous medications, with a focus on radiopharmaceuticals used in nuclear medicine. Medication administration errors pose a significant challenge to patient safety. The "five rights" framework-ensuring the right patient, drug, time, dose, and route-serves as a cornerstone for safe drug administration. In the context of radiopharmaceuticals, notable for their use in nuclear medicine, adherence to these principles is paramount due to their unique properties and role in diagnostic and therapeutic procedures. The article explores the impact of container materials, particularly in syringes, on radiopharmaceutical stability and administration accuracy. It delves into the complexities of sorption phenomena, highlighting studies demonstrating its occurrence and potential consequences, including variations in administered doses and compromised diagnostic or therapeutic outcomes. Noteworthy factors influencing sorption include the type of radiopharmaceutical, container composition, molecular properties, and dilution. Findings revealing residual activity in syringes and identifying specific components, such as lubricants, silicon gaskets, and plungers, contributing to adsorption are presented. Migration of metal contaminants from container to content is discussed, emphasizing the potential impact on radiochemical yield and stability. There is a need for comprehensive studies to characterize drug-container interactions and poses crucial questions about the true benefit patients derive from prescribed activities. It challenges current practices, suggesting a need for tailored activity levels, container validation protocols, and rigorous testing of hospital preparations. Ultimately, this perspective paper calls for a deeper understanding of these interactions, urging regulatory consideration and standardization to ensure optimal drug administration and patient outcomes.

Evaluating Clinical Safety and Analytical Impact of Subvisible Silicone Oil Particles in Biopharmaceutical Products.

Silicone oil is a commonly used lubricant in pre-filled syringes (PFSs) and can migrate over time into solution in the form of silicone oil particles (SiOPs). The presence of these SiOPs can result in elevated subvisible particle counts in PFS drug products compared to other drug presentations such as vials or cartridges. Their presence in products presents analytical challenges as they complicate quantitation and characterization of other types of subvisible particles in solution. Previous studies have suggested that they can potentially act as adjuvant resulting in potential safety risks for patients. In this paper we present several analytical case studies describing the impact of the presence of SiOPs in biotherapeutics on the analysis of the drug as well as clinical case studies examining the effect of SiOPs on patient safety. The analytical case studies demonstrate that orthogonal techniques, especially flow imaging, can help differentiate SiOPs from other types of particulate matter. The clinical case studies showed no difference in the observed patient safety profile across multiple drugs, patient populations, and routes of administration, indicating that the presence of SiOPs does not impact patient safety.

Pharmacokinetics-Bridging Between Autoinjectors and Prefilled Syringes for Subcutaneous Injection: Case Examples Revealing a Knowledge Gap.

Comparative pharmacokinetics (PK) studies have efficiently served as the bridge between autoinjectors and prefilled syringes given the underlying principles that comparable exposure could translate to comparable efficacy and safety. This article discusses approaches used to address uncertainties associated with the observation of noncomparable PK leading to the successful introduction of new autoinjector devices for monoclonal antibody and Fc-fusion protein products. Information from seven case examples suggests a knowledge gap that warrants attention in autoinjector development.

Origami-Based Haptic Syringe for Local Anesthesia Simulator.

Although medical simulators have benefited from the use of haptics and virtual reality (VR) for decades, the former has become the bottleneck in producing a low-cost, compact, and accurate training experience. This is particularly the case for the inferior alveolar nerve block (IANB) procedure in dentistry, which is one of the most difficult motor skills to acquire. As existing works are still oversimplified or overcomplicated for practical deployment, we introduce an origami-based haptic syringe interface for IANB local anesthesia training. By harnessing the versatile mechanical tunability of the Kresling origami pattern, our interface simulated the tactile experience of the plunger while injecting the anesthetic solution. We present the design, development, and characterization process, as well as a preliminary usability study. The force profile generated by the syringe interface is perceptually similar with that of the Carpule syringe. The usability study suggests that the haptic syringe significantly improves the IANB training simulation and its potential to be utilized in several other medical training/simulation applications.

[Check valves : Important facts for safe use]. / Rückschlagventile : Wissenswerte Eigenschaften für die sichere Anwendung.

Patients benefit from the use of check valves when drugs with a particularly short half-life (e.g., catecholamines) are continually administered through a one-way valve or when an accidental retrograde bolus application must be prevented, as in the event of a rapid sequence induction and intubation. The lack of a check valve can prevent the administered drug from working in the intended manner resulting in potentially insufficient treatment and negative consequences for the patient. In order to ensure the highest level of patient safety while using check valves appropriate training of medical personnel is essential. In contrast, preventable dangers (e.g., infections, awareness) exist when safety measures are disregarded, including the re-use of medications, syringes or disposable materials in successive patients after having only exchanged the check valves. It is not clear how often this is practiced in German-speaking areas.

A Randomized, Open-Label Study Conducted to Evaluate the Bioequivalence of Pegfilgrastim-cbqv On-Body Injector Versus Prefilled Syringe in Healthy Male Participants.

INTRODUCTION: To help prevent febrile neutropenia, pegfilgrastim-cbqv (UDENYCA®; Coherus BioSciences), a pegfilgrastim (NEULASTA®; Amgen) biosimilar, is administered 24-96 h after myelosuppressive chemotherapy. Delivery of pegfilgrastim-cbqv using an on-body injector (OBI) provides an alternative method of administration, affording options in drug delivery. This study aimed to establish pharmacokinetic (PK) and pharmacodynamic (PD) bioequivalence and assess the safety of pegfilgrastim-cbqv administered using an OBI compared with a prefilled syringe (PFS). METHODS: In this open-label, two-period crossover study, healthy adult male participants (N = 189) were randomly assigned 1:1 to receive pegfilgrastim-cbqv 6 mg subcutaneously using an OBI (n = 92) or a PFS (n = 95) in period 1 and then an injection via the other method in period 2. Primary PK end points were area under the concentration-time curve from time 0 to infinity, area under the concentration-time curve from time 0 to the last quantifiable concentration, and maximum plasma concentration. Secondary PD end points, safety, immunogenicity, and tolerability were also assessed. RESULTS: The 90% confidence intervals (CIs) of the geometric mean ratios for the PK and PD end points fell within the predetermined range (80-125%), indicating PK and PD bioequivalence between pegfilgrastim-cbqv OBI and pegfilgrastim-cbqv PFS. Treatment-emergent adverse events (TEAEs) occurred in 87.8% and 75.8% of participants in the OBI and PFS groups, respectively. Most TEAEs were musculoskeletal effects. The most common OBI-related TEAE was injection site erythema (31.7%), which was mild, transient, and self-limiting. The incidence of treatment-emergent antidrug antibodies (ADAs) was similar between the OBI and PFS. ADAs had no apparent impact on PK, PD, or safety. Neutralizing antibodies were not detected in any participant. CONCLUSIONS: Results of the study showed PK and PD bioequivalence of pegfilgrastim-cbqv administered using OBI compared with PFS. OBI and PFS administration had similar safety, tolerability, and immunogenicity profiles. No unexpected safety signals were identified. Graphical Abstract available for this article.

Febrile neutropenia is when a patient has a fever and a lower-than-normal number of white blood cells. When white blood cell counts are low, patients are more susceptible to opportunistic infections as a result of their weakened immune systems. Severe febrile neutropenia can lead to the stopping or delaying of chemotherapy. The drug pegfilgrastim-cbqv is used 24­96 h after chemotherapy to stimulate the growth of white blood cells. Pegfilgrastim-cbqv is available in a single-dose prefilled syringe and in a prefilled autoinjector. If a patient cannot inject themselves with the drug, they must go to a clinic for the injection. Using an on-body injector applied to the skin that automatically injects the drug at a specific time could eliminate the need to go to the clinic. During this study, healthy adult male participants were given pegfilgrastim-cbqv through an on-body injector or a prefilled syringe to investigate if the movement of the drug into, through, and out of the body (pharmacokinetics) and the physiological action of the drug in the body (pharmacodynamics) were similar between the two injection methods. Side effects were also studied. The researchers found that the pharmacokinetics and pharmacodynamics for pegfilgrastim-cbqv given by on-body-injector or prefilled syringe were similar. The number and types of side effects were also similar. The most common side effect for the on-body injector was mild erythema at the injection site. This side effect resolved by itself. The treatment benefit and safety of pegfilgrastim-cbqv were very similar regardless of how the drug was administered.

Characterization and Assessment of Physical Properties of 3 Single Syringe Hydraulic Cement-based Sealers.

INTRODUCTION: A number of sealers with different chemistries are badged as Bioceramic, implying biological activity, but have dissimilar properties, which has implications on the sealer properties and will affect the quality and outcome of root canal treatment. This study aimed to assess the physical and chemical properties of 3 hydraulic cement-based sealers, namely BC Universal sealer compared with Totalfill BC sealer and AH Plus Bioceramic. METHODS: The microstructure and composition of the sealers were assessed using scanning electron microscopy and energy dispersive spectroscopy after setting. The crystalline phases were assessed by X-ray diffraction analysis and the leachates were tested using inductively coupled plasma. All testing was performed at 0, 7, and 28 days. The physical properties of film thickness, flow, radiopacity, and solubility were evaluated using ISO 6876:2012 standards. RESULTS: All 3 sealers contained calcium, zirconium, and silicon. Totalfill BC had the highest calcium release at 7 and 28 days followed by AH Plus Bioceramic and BC Universal sealer. All 3 sealers adhered to the ISO standard in terms of flow and radiopacity. BC Universal sealer was slightly over the range (>50 µm) for film thickness. All sealers exceeded the solubility range set by ISO 6876:2012. CONCLUSION: Although these hydraulic cement sealers had similar components and delivery, the properties varied significantly. The testing of material properties to confirm the suitability for clinical use is necessary.